Empty Nose Syndrome

Evidence Based Proposals for

Inferior Turbinate Management

Eugene Barton Kern

George M. and Edna B. Endicott Professor of Medicine Emeritus,
Mayo Foundation for Medical Education and Research,
Rochester, Minnesota, United States
Professor, Rhinology and Facial Plastic Surgery Emeritus,
Mayo Clinic School of Medicine
Clinical Professor, Department of Otorhinolaryngology
Head and Neck Surgery, State University of New York (SUNY),
Buffalo, New York, United States
Director and Vice President, Gromo Foundation for Medical
Education and Research, Buffalo, New York, United States

Oren Friedman
Director, Facial Plastic Surgery,
Associate Professor,
Otorhinolaryngology Head & Neck Surgery,
University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania, United States
Empty Nose Syndrome ISBN: 978-0-443-10715-3
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For my darling wife Ruthie, our children, and grandchildren. Yours,
mine, ours. evermore. EBK
To my family, whose love and encouragement empower
me.everything I do, I do for you. OF
In large measure, this book is also dedicated to our patients, trusting
that we will care for them with knowledge, integrity, and compassion
for their well-being and happiness. Thus, it is our dedication.
Foreword

When, in the middle and late 19th century, specialization in medicine started, rhinol-
ogy gradually developed as a separate specialty and became part of the Triological
Oto-Rhino-Laryngology. In the early years of the new specialty, various surgical
procedures and new instruments were developed; among them were the surgical
reduction and resection of the inferior and the middle turbinate. It soon turned
out, however, that resecting parts of the turbinates had to be performed conserva-
tively and with care as these structures play an essential role in nasal function.
Even partial resection of those physiological important structures may lead to per-
manent complaints. Eugene B. Kern, Professor of Rhinology at the Mayo Clinics,
was one of the first to stress the need to be careful and conservative in reducing
the nasal turbinates. A too wide nasal cavity produces various permanent com-
plaints, symptoms that were coined by him the “Empty Nose Syndrome.” His lec-
tures and writings about this syndrome have been of historical importance and
have led to the awareness among otorhinolaryngologists to treat the nasal turbinates
with care.

Egbert Huizing, MD, PhD

Professor Emeritus of The University
Medical Centre Utrecht, The Netherlands
Chair Department of Oto-Rhino-Laryngology, 1980-1998
Laren, The Netherlands
October 2022

xi
Preface

Our goal with this text is to create an awareness of the empty nose syndrome (ENS)
among physicians, surgeons, and patients.
After subject exploration, new understandings were realized allowing us to advo-
cate treatment recommendations for patients with ENS, strategies for preventing
ENS, and certain evidenced-based proposals for treating the turbinates, especially
the inferior turbinates, so as to avoid ENS.
First, we validate our patients’ experiences by broadcasting loudly that the ENS
exists. Yes, it is a true clinical entity that frequently occurs subsequent to “exces-
sive,” iatrogenic, and “trauma” to turbinate tissue. The true incidence of ENS after
therapeutic turbinate “trauma” is unknown, although with our experience, it is not as
“rare” as some assume.
In 2020, on the American Rhinologic Society website, the following quotation
appeared specifically speculating; suggesting that there are thousands of patients
with the ENS.
“The exact incidence of ENS is currently unknown. There are still thousands of
patients experiencing ENS.” (Bold italics added)
Second, for us, the primary purpose for inferior turbinate surgery is to reduce
nasal airway obstruction (improve breathing), all the while preserving nasal function
and preventing the scourge of the ENS. To this end, we offer reflections regarding
evidence-based management of breathing difficulty secondary to pathology of the
inferior turbinate in both adults and children. Realize, from the literature and our
own (anecdotal) experience, of performing “conservative” turbinate surgery that
adding an adequate inferior turbinate out-fracture (lateralization), the nasal airway
can be effectively enlarged and maintained (durable) for a “prolonged” period
(time).212,246e250,252,254
Third, we condense and concentrate much of the known knowledge into this sin-
gle “comprehensive” resource, so practitioners may review diagnosis, etiology, and
treatment (medical and surgical) of this underappreciated syndrome (ENS) along
with the risks associated with aggressive turbinate excision, especially when nasal
physiology is often seemingly slighted so we offer a brief summary of the “latest”
principle “purposes” of the human nose.
Ideally, all our clinical decisions should be based on evidence-based medicine
(EBM), a subject that we review in this book, recognizing the supremacy of the ran-
domized controlled trial (RCT); however, when data from a RCT are limited, incom-
plete, inconclusive, conflicting, or starkly nonexistent, there is no choice but to rely
upon clinical reasoning, the rationalism of “clinical judgment,” yet awareness of a
possible flawed conclusion must always be kept in mind.280
The all-inclusive concept of EBM underscores the difference between decisions
based on hard scientific evidence from well-designed and competent RCTs as
opposed to decisions based on expert opinion.

xiii
xiv Preface

Recall that in 2013, Prasad et al., from the National Institute of Health (NIH),
asserted that, “the reversal of established medical practice is common and occurs
across all classes of medical practice.” In fact, these investigators documented
that 146 (40.2 %) of certain formerly “validated” established medical practices
(they reviewed 2044 original articles) were reversed (discontinued); vexing is the
unexpected realization that practices previously believed “rational” and “logical”
were ultimately proven to be flawed, useless or harmful.274
As physicians and surgeons, all clinicians, we are duty-bound “to do the best we
can” for our patients within the boundaries of prevailing knowledge, understanding
that “good” medicine utilizes the current “best information available,” allowing for
“educated guesses,” which is obviously subject to alteration, as medical dogmas and
practices are subject to continuous change, corrections with amendments, adjust-
ments, and improvements since that’s the actual course of medical progress, the
ever minting of a new and current “approximate temporary truth.”326
As adroitly pointed out by Sergio Cocchei (2017) in his paper, “Error, contradic-
tion and reversal in science and medicine,” the concept of “approximate temporary
truth” was introduced by, the esteemed philosopher of science, Professor Sir Karl
Raimund Popper (1902e1994). Professor Popper reflected on the temporal quality
of “truth” since biomedical research and clinical practice have witnessed, as Prasad
et al. (2013) has exposed, numerous examples of reversals and rejections of once
dearly and “rationally” held beliefs.274,326
By definition, surgery is the medical practice of managing diseases, deformities,
and injuries by actually “cutting” into a part of the body while, on the other hand,
electrocautery, chemocautery, lasers, radiofrequency, coblation, or ultrasound is
not surgery in the traditional “strict sense” of “cold knife” cutting, but nonetheless
they are currently covered beneath the umbrella of “surgery,” although we prefer to
label them “nonsurgical” procedures.
We think that with a physiologic understanding, practitioners pursuing inferior
turbinate reduction have an unambiguous obligation to preserve the pseudostratified
epithelial mucociliary transport system, minimizing submucosal (lamina propria,
stroma) neurovascular damage; thereby avoiding adverse physiologic penalties,
with resultant sequelae, all the while improving nasal breathing function.
Consequently, in our opinion, “cold knife” techniques have the edge for now,
avoiding thermal trauma as submucosal vascular choking fibrosis deprives the over-
lying epithelium with the necessary nutrition to maintain normal mucociliary trans-
port; depriving the moisture necessary for charging the inspired air with heat and
humidity; permitting optimal exchange of O2eCO2 at the alveolar level.
The final arbitrator, “Father Time,” must “weigh in” before issuing a “final” adju-
dication (concrete guidelines) regarding turbinate surgery.
For “today” only, treatment options for the inferior turbinate are limited since
guidelines from quality RCTs are presently nonexistent for children, so we offer
our own “approximate temporary truth.” For now, we suggest that submucosal
resection (microdebrider-submucosal) and inferior turbinoplasty (without bony
resection unless conchal enlargement) with out-fracture (lateralization) as the
 Preface xv

most rational current conservative surgical alternative, after failed medical therapy;
suggested by Argenbright et al.333 (2015) for children; reinforced by Passali et al.’s
(1999, 2003) prospective randomized trial in adults (N ¼ 382) with data collected
before intervention and at four years and six years after intervention.212,218
For adults, with evidence-based treatment proposals in mind, it was Larrabee
and Kacker267 who reviewed five studies that they rated as level 1 evidence, prospec-
tive and randomized trials. These include the following notable evidence-based
treatment contributions including: “cold knife” submucosal resection of inferior
turbinate tissue (turbinoplasty), radiofrequency treatment, microdebrider-assisted
turbinoplasty, and ultrasound turbinate reduction.26,27,212,232,237
The evidence-based treatment proposal for “surgical” management of the infe-
rior turbinate(s) favored by Larrabee and Kacker267 was the laudable paper pre-
sented by Passali et al. (1999, 2003) who reported on the randomized outcomes
for all their adult patients (N ¼ 382) having nasal airway obstruction, secondary
to inferior turbinate enlargement (“hypertrophy”) who were refractory (“failed”)
to medical management and treated with various procedures including: electrocau-
tery, cryotherapy, laser cautery, submucosal resection without lateral displacement-
out-fracture, submucosal resection with lateral displacement, and turbinectomy.
They performed objective testing including rhinomanometry and acoustic rhinome-
try plus measuring mucociliary transport times and determining levels of secretory
immunoglobulin A.212,218
And in the words of Passali et al.:
“These data indicate that submucosal resection with lateral displacement of the
inferior turbinate results in the greatest increases in airflow and nasal respiratory
function with the lowest risk of long-term complications.” 212
“After 6 years, only submucosal resection resulted in optimal long-term normal-
ization of nasal patency and in restoration of mucociliary clearance and local
secretory IgA production to a physiological level with few postoperative compli-
cations (p < .001).” 212
As a consequence of these findings, Larrabee and Kacker267 recommended Pas-
sali et al.’s inferior turbinate submucosal resection (turbinoplasty) combined with
out-fracture (lateral displacement) as the first-choice technique for treating inferior
turbinate enlargement (“hypertrophy”).212,218 This inferior turbinate submucosal
resection (turbinoplasty) may be accomplished by either a “cold knife” or with a
microdebrider.
We submit to you, our perspectives for your consideration, recognizing that our
collective rhinologic knowledge was earned by the tangible experience of caring for
countless thousands of rhinology patients and specifically treating more than 300
souls suffering with the ENS.

The Authors 2023

Acknowledgments

A very special appreciation goes to Monika Stenkvist Asplund, M.D., Ph.D. Asso-
ciate Professor Emerita, Department of Otorhinolaryngology Head and Neck Sur-
gery, Uppsala University, Uppsala, Sweden, who, with her extraordinary
observational powers, as a visiting surgeon and scientist to the Mayo Clinic in
1994, was the first to say, “Dr. Kern, that nose looks empty.” With that moniker, a
syndrome begot a name.
The authors also acknowledge two indispensable colleagues, Joyce R. Mc Fad-
den, MLS, AHIP, Librarian and Julie A. Swenson, Interlibrary Loan Coordinator of
the Mayo Clinic Libraries and Historical Unit, Rochester, Minnesota, who skillfully
and with great alacrity, orchestrated the collection of over 300 original papers and
booksdsome in French, others in Dutch and Germandfrom the Mayo collection
and by interlibrary loan; a most grateful thank you to you both; we could not
have effectively accomplished this work without you.
It was the steady guiding hands of Tracy Tufaga, Editorial Project Manager,
Swapna Srinivasan and Kiruthika Govindaraju Project Managers at Elsevier who
“stewarded” us properly through the minefields of permissions, copyrights, and
other assorted challenges before attaining the dream, a beautiful finished polished
product, the “book.” So, it is with great appreciation for all you quietly and
competently did and do; we humbly offer one major magnificent thank you.
Additionally, this work was immeasurably enhanced by the knowledgeable assis-
tance of Michael A. Hohberger, who provided effective editorial advice.
Moreover, we owe a great debt of gratitude to our teachers, colleagues, and stu-
dents who collectively imbued in us the rank of absolute integrity, assertive curiosity,
insistent skepticism, the virtue of conscientiousness, and a sublime compassion for
the human condition and all that entails.
We are exceptionally appreciative that this work was partially funded by an
educational grant from: The Gromo Foundation for Medical Education and
Research, Buffalo, New York.
The Authors 2023

Data Sources
Materials for this book were identified by PubMed database, Medline, Google,
Wikipedia, YouTube, and the lay press merging the literature searches up to and
including January 1, 2023.

Review Methods
References were evaluated and chosen if they directly addressed aspects of nasal
physiology, the empty nose syndrome (ENS) or indirectly discussed sequalae (side
effects) of nasal procedures producing symptoms consistent with ENS including
both surgical turbinate resections (complete, partial, and turbinoplasty procedures)
and nonsurgical turbinate reduction adjunctive procedures (n-sTRAP) producing
xvii
xviii Acknowledgments

symptoms consistent with the protean symptoms seen in ENS. We searched for perti-
nent papers based on the guidance for conducting methodological reviews.1 This
type of review represents a distinct “literature synthesis method,” and its methodol-
ogy remains relatively underdeveloped. The eligibility criteria were limited to books
and papers published, translated or referenced in the English language, although
some papers were translated from the original language of publication.
It is possible that we may have unintentionally introduced a selection bias and
regrettably, some important papers may have been inadvertently omitted. For this
we, the authors, apologize.
 CHAPTER

Introduction and overview

1
1. Introduction and overview
Debate concluded, the empty nose syndrome (ENS) exists. ENS was initially recog-
nized and formally presented to the profession by the Mayo Clinic team in 1994.
With over a quarter of a century experience of treating hundreds of patients devas-
tated by ENS, we reexamined the existing thinking concerning the etiology, differ-
ential diagnosis, diagnosis, treatment, and ultimately preventing this crippling
disorder.
We found more than 60 specific citations exclusively for the ENS on the PubMed
database. With our own, more than 300 ENS patients and conceivably countless
others in the United States of America, feasibly approaching thousands globally
including reports in the medical literature and on the World Wide Web from Africa,
Canada, Chile, China, France, Germany, Israel, Italy, Korea, Malaysia, the Middle
East, the Netherlands, Portugal, Russia, Spain, and Turkey posing the question, is
ENS really a rare condition?
In 2020, on the American Rhinologic Society website, the following quotation
appeared specifically speculating, suggesting that there are thousands of patients
with the ENS.
“The exact incidence of ENS is currently unknown. There are still thousands of
patients experiencing ENS.”
Moreover, the Internet is awash with numerous patient posts regarding their ENS
symptoms along with support websites for the “postnasal surgery dysfunction com-
munity” including: https//www.change.org/emptynose, https://www.usasinus.org/
empty-nose-syndrome and https://www.nasalcripple.com.
In this chapter, we offer an introduction and overview of the subject, ENS, high-
lighting subjects we will consider in detail with corresponding citations from the
literature (broad bibliography of 376 references), besides providing complete com-
mentary regarding the fundamental features of ENS along with a review of pertinent
nasal physiology, a comprehensive differential diagnosis and an analysis of the
various medical, surgical, and psychological treatment options for these desperately
distraught patients, some of whom, have committed suicide because of their horrific
torment.

Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00001-9 1

Copyright © 2024 Elsevier Inc. All rights reserved.
2 CHAPTER 1 Introduction and overview

ENS is frequently initiated by an iatrogenic traumatic violation of the physio-

logic integrity of the nasal mucosa and submucosal structures of the turbinates
inducing a secondary atrophic rhinitis. The nasal mucosa, “the organ of the
nose,” comparable to all human organ systems, has limits to its functional capacity
before failure ensues; therefore, recommendations for both inferior and middle
turbinate management to evade and prevent the calamity of ENS are considered
and presented.
For example, apropos the middle turbinate, we champion saving it for both its
physiological function and as a crucial anatomical landmark unless reduced or
destroyed by polypoid disease concomitant to chronic rhinosinusitis, then removal
of variable amounts of polypoid tissue is required along with the inadvertent and un-
intended concomitant turbinate tissue resection. Most unfortunately, since there is
no hard scientific evidence, no evidence-based medicine (EBM) imperative of a ran-
domized controlled trial (RCT), we awkwardly and regrettably must rely on the
potentially biased and placebo effect prone possibilities of expert opinion.
Regarding the inferior turbinate, with today’s “approximate temporary truth,”*
the inferior turbinate should also be totally preserved at best; out-fracture (laterali-
zation) is one of the non-surgical Turbinate Reduction Adjunctive Procedures
(n-sTRAPs), as an attractive atraumatic alternative with some evidence if performed
“adequately” can be very effective in maintaining a fixed lateral position contrary to
and divergent from some citations in the literature.
*The term, “approximate temporary truth,” is from Professor Sir Karl Raimund
Popper (1902e1994), the Austrian-British philosopher of science, from his 1959
book “The Logic of Scientific Discovery” Basic Books, Inc. New York translated
from the German “Logik der Forschung” by the author with assistance of Dr.
Julius Freed and Lan Freed. His assertions regarding science are extremely
revealing: “Science is not a system of certain, or well-established statements;
nor is it a system which steadily advances towards a state of finality. Our science
is not knowledge (episteme): it can never claim to have attained truth, or even a
substitute for it, such as probability. Yet science has more than mere biological
survival value. It is not only a useful instrument. Although it can attain neither
truth nor probability, do striving for knowledge and the search for truth are still
the strongest motives of scientific discovery. We do not know: we can only guess.”
(Italics not added) Those lines are quoted directly and exactly from “The Logic
of Scientific Discovery” page 278.
Specifically, surgery is: the medical practice of managing diseases, deformities,
and injuries by actually “cutting” into a part of the body, while, on the other hand,
electrocautery, chemocautery, lasers, radiofrequency, coblation, or ultrasound are
not surgery in the traditional sense of cold knife “cutting,” but nonetheless they
are currently considered “surgery” by some authors, we choose to call these prac-
tices the non-surgical turbinate reduction adjunctive procedures (n-sTRAPs).
If a more assertive surgical intervention to improve nasal breathing is required,
then focus intervention exclusively at the inferior turbinate head (the posterior
 1. Introduction and overview 3

portion of the critical internal nasal valve area) as a very limited submucosal micro-
debrider turbinoplasty that can be complemented with an inferior turbinate out-
fracture (lateralization). With an affirming nod to evidence based medicine
(EBM), this strategy is supported by two papers, with level one evidence of a ran-
domized controlled trial (RCT), from the literature.
Most assuredly, aggressive surgery to the lateral wall of the nose, including the
middle and inferior turbinates, is indicated and justified for inverting papilloma, ju-
venile angiofibroma, and a number of malignant disorders, which may unfortu-
nately also result in symptoms of the ENS.
Total inferior turbinectomy for inferior turbinate enlargement (“hypertrophy”)
has been condemned by a number of surgeons and baptized a nasal crime by two
European academic authors with whom we are totally in agreement. We state un-
equivocally that total inferior turbinectomy for inferior turbinate enlargement (“hy-
pertrophy”) is a nasal crime, especially in children without the benefit of a
well-designed RCT or without future follow-up into the years of adulthood.
Total inferior turbinectomy was trumpeted and supported by some surgeons on
the “other side” of the divide who claimed they never observed the long-lasting signs
and symptoms of persistent nasal airway obstruction, crusting, postoperative pain,
and emotional issues including depression and anxiety seen in the multitude of
ENS patients after total or near total (subtotal) inferior turbinectomy for inferior
turbinate enlargement (“hypertrophy”).
It is clear that the optimal turbinate management lies in prevention to avoid the
catastrophic calamity of ENS. Unfortunately, it is unknown, at the present moment,
as to the precise amount of nasal mucosa and submucosa that must be preserved dur-
ing intranasal turbinate procedures to prevent ENS. Therefore, we should always
minimize turbinate manipulation with attendant mucosal and submucosal damage
whenever possible, especially radical excision of the turbinate(s) unless absolutely
mandatory dictated by specific pathology as noted above.
The ideas behind EBM comes from the “father” of EBM, David Sackett, MD.
EBM is primarily about discovery of the “best medical evidence,” for crafting clin-
ical choices, judgments, and rational therapeutic decisions in the best interest of the
patient. The entire concept of EBM is the distinction between decisions based on
hard scientific evidence from well-designed and competent RCTs as opposed to de-
cisions based on expert opinion.
Unvalidated therapies need scrutiny with attempts at verification with proof
before being embraced and approved as sensible and successful or discarded as use-
less or harmful. Proof is obtained through well-conceived and well-done RCTs,
which avoid bias and are absolutely indispensable for intelligently comparing
competing medical practices.
The time-honored bedrock of principled moral care of patients requires that
unvalidated care must not be undertaken unless in a structured evidence-based
RCT. The ideal double-blind placebo-controlled trial cannot easily be applied to sur-
gical comparisons, but the optimal design of RCTs for surgery must be attempted
nonetheless.
4 CHAPTER 1 Introduction and overview

We believe that in well-done RCTs, blinding is possible for surgical and proce-
dural studies when the operator remains “silent” as to his/her specific involvement
with subjective and objective outcome studies performed by blinded evaluators-
coded study.
With the emergence of EBM and its reliance on RCTs, it was soon recognized
that the results of the RCTs were not generalizable, meaning that these RCTs results
were not widely transferable from the broad trial study population to a specific
unique individual surgical patient; therefore, surgeons lost their enthusiasm for
the soul of EBM, the RCT.
As recently as 2015, it was determined that RCTs in the ENT literature are under
4% because they are difficult, regularly expensive, and at times ethically challenging
to perform, and observational studies are utilized more frequently with a retrospec-
tive investigation to make connections concerning treatment effectiveness, which
then can be followed by confirmatory studies.
CONSORT stands for, CONsolidated Standards Of Reporting Trials, which is a
uniform method of reporting RCTs that markedly improve trial methodological con-
struction thereby avoiding publishing flawed studies. CONSORT was developed to
promote consistency, clarity, accuracy, and transparency of reporting of RCTs. Un-
fortunately, it was found as recently as 2015 that the reporting quality of ENT jour-
nals was considered “suboptimal” and could be improved especially by using the
CONSORT requirements.
Propensity score matching (PSM), propensity score systems can be used in
observational studies to decrease a confounding variable; an indication of bias.
When performed with proper methodology using PSM, it is possible to obtain results
that “approximate” a “randomized prospective study.”
Clinical practice guidelines (CPGs) require authoritative judgments from various
individuals, thereby potentially introducing bias and a possible conflict of interest
(COI). When and if the data from RCTs are limited, incomplete, inconclusive, con-
flicting, or starkly nonexistent then contemporary CPGs and or advisories are often
relied upon for an honest expert opinion as to how to proceed caring for a unique
individual patient.
There are twofold reasons that medical therapies decline in approval and are no
longer used:
(1) Replacement occurs when a practice is displaced by one that is better.
(2) Reversal (discontinued) occurs when a practice is withdrawn when it is realized
that the practice was never really successful or it was discovered to be harmful,
it is then reversed. The solution to a reversal is finding the answer by RCTs.
Preferably, questionable medical practices are replaced by better ones, based
on strong and substantial comparative trials (RCTs) where new practices
overtake older ones inaugurating novel canons and new standards of care. In
fact, it is well-known that once “time-honored” medical and surgical practices
are repeatedly reversed (discontinued), which is the nature of medical prog-
ress. In 2013, several investigators, in a 10-year review of the literature, found
 1. Introduction and overview 5

146 (40.2%) verified and validated medical practices that were reversed, no
doubt, at first, those practices seemed logical and exquisitely rational when in
fact they were ultimately flawed.
Medical journals are extremely influential voices in setting standards for accept-
ing and adjudicating submitted research to accurately and unbiasedly update the pro-
fession. The unwritten covenant with peer reviewers and their editors is that they all
act in the best interest of the profession, ultimately, for the best interest of the patient.
Recently, in 2019, a comprehensive search for tools for determining the quality of
peer review reports was undertaken. Assessors of the peer review process asked:
1. Is peer review: a flawed process at the heart of science and journals?
2. Who reviews the reviewers?
3. Editorial peer reviewers’ recommendations at a general medical journal: are they
reliable and do editors care?
4. Rereviewing peer review.
5. Peer review for biomedical publications: we can improve the system.
6. Make peer review scientific.
7. Custodians of high-quality science: are editors and peer reviewers good enough?
Realizing the need for validated tools that define the quality of peer-reviewed
research reports, investigators found 24 tools: 23 scales and one checklist, which
could define the quality of peer review reports. It was noted there was no single
tool that defined the word “quality”. They concluded that the contemporary tools
available for assessing peer review quality are of questionable validity.
“Several tools are available to assess the quality of peer review reports; however,
the development and validation process is questionable and the concepts evalu-
ated by these tools vary widely.”
Some studies have found that the peer reviewer’s competence, especially in
biostatistics, and overall capability to uncover errors and detect reporting defi-
ciencies is unacceptably wanting. Other studies showed that the need is urgent for
improving the quality of peer review reporting and for finding instruments (tools)
for evaluating and improving the quality of those reports.
The consequences of the reviewer’s findings are obviously critical, requiring
astute interpretative rigor, comprehension and understanding of the scientific
work, and an operational understanding of statistical analysis, so the editorial deci-
sion is scientifically justified. The outside investigators plan to survey journal editors
and authors alike by initiating and managing an international online survey
regarding the quality of peer reviewer’s reports for developing new evaluation tools
that can be used for appraising interventions aimed at improving the peer review pro-
cess especially in the analysis of RCTs.
The first International Peer Review Congress was held approximately about 30
years ago and is still on going as in 2017, David Moher presented a plenary talk at
the eighth International Congress on Peer Review and Scientific Publication (below)
6 CHAPTER 1 Introduction and overview

entitled: “Custodians of High-Quality Science: Are Editors and Peer Reviewers

Good Enough?” https://www.youtube.com/watch?v¼RV2tknDtyDs&t¼454s.
According to several investigators, there has been an increase in plagiarism,
deception, and malfeasance with falsification of data and inappropriate statistics
in some recently published medical journals. We must all be alert to possible crimes
and misdemeanors in the name of medical research, never naı¨ve please.
Regarding children, we think, surgeons operating on the turbinates of children
have an explicit moral and ethical obligation to the follow, report, and publish on
the trajectory of these children as they passage into adulthood. Considering turbinate
surgery in children, some responsible colleagues concluded that:
“There is currently little evidence to support turbinate reduction surgery in chil-
dren. The role of surgery, if any, has not been properly examined. Furthermore,
the long-term effects on nasal airflow dynamics, nasal physiology, and long-
term complications remain to be studied.”
Today, if pediatric surgery is indicated, some type of “conservative” turbino-
plasty is the plausible treatment of choice, for those children failing the mandatory
three month trial of intense medical management. Microdebrider submucosal infe-
rior turbinoplasty (most often without bone resection) but with additional out-
fracture (lateralization) of an inferior turbinate makes the most sense at this juncture
without guidance from any RCTs. Until well-executed RCTs are available, we along
with others caution the profession not to remove turbinates in children, since meager,
if any, evidence exists supporting any type of turbinate reduction surgery in this pop-
ulation. A position that we unequivocally and wholeheartedly support despite jour-
nal reports of total inferior turbinectomies in children.
Ultimately, when considering any “new” innovative procedure or “reevaluation”
of a current procedure, we think that it is necessary to inaugurate a formal approach
for developing an RCT for bias elimination and placebo control, by creating an
authorized research protocol to answer the question following the CONSORT state-
ment. This applies to all future treatment approaches to the middle and inferior tur-
binates, except for the study by Professor Desiderio Passali and associates
(n ¼ 328), with an inferior turbinate RCT, followed and reported after four and
six years, respectively, the profession still lacks confirming RCTs with long-term
follow-up (measured in years) for both adults and children to avoid the tragic calam-
ity of the “ENS.” This importantly noteworthy study by Passali et al. is cited and
discussed in detail later in the text.
Medicine utilizes the “best information available” at the time, allowing for
“educated guesses,” with rejections of once dearly held beliefs, which, of course,
is always subject to change. We physicians and surgeons should tolerate “uncer-
tainty” acknowledging the reality that medical theories and practices are subject
to dislocation, disruption, and unceasing modification and improvements because
that’s the nature of medical and scientific advancement.
 2. Empty nose syndrome (ENS) in print media, TV 7

Since, according to Professor Sir Karl Raimund Popper’s concept of “approxi-

mate temporary truth,” as noted above, we cannot know truth and can only guess;
therefore, we can only approximate the truth. The approximation of truth that holds
authority today is only temporary because it may be replaced tomorrow by an alter-
native and superior “approximate temporary truth.” This concept of “approximate
temporary truth” powers the engine of scientific progress from leeches, purges,
and bloodletting to antibiotics, DNA, deoxyribonucleic acid, proton beam therapy,
and gene-editing, clustered regularly interspaced short palindromic repeats,
(CRISPR) “genetic engineering”.

2. Empty nose syndrome (ENS) in print media, TV; with

ubiquity on the World Wide Web
Just as in the Dostoyevsky novel, Crime and Punishment, an individual surgeon
faces a moral crisis after performing a total turbinectomy, subsequently realizing
the tangible adverse consequences to the patient and eventually recoiling with
disgust at the deed and experiences a titanic internal struggle with the horror and
guilt for performing such an abhorrent surgical act.
We ask, can a profession collectively come face to face, with such a moral crisis,
about performing a total inferior turbinectomy? What about “lesser” inferior turbi-
nate procedures?
Long ago and not so far away at the University of Nebraska, in 1985, G. F. Moore
and colleagues published, in the journal The Laryngoscope, their observations after
an extended patient follow-up of 3e5 years, following total inferior turbinate resec-
tion, they ended their journal abstract with the subsequent two analytical critical,
compelling sentences. “In this study, patients who had previously undergone total
inferior turbinectomy were evaluated with the use of an extensive questionnaire.
It confirms that total inferior turbinectomy carries significant morbidity and should
be condemned.”2 (Bold italics added)
Going beyond condemnation, Egbert Huizing and John de Groot, from the
Netherlands, writing on page 300 of their well-received Functional Reconstructive
Nasal Surgery, second edition 2015, Thieme Publishers, roared denunciation again,
as in their first edition, 2003, that, “Total turbinectomy must be considered a nasal
crime”.3,4 (Bold italics added)
The discussion of the ENS is no longer limited to arcane debates at obscure med-
ical meetings or an occasional report in the literature of the occult. The ENS is now
in the public domain and has been for some time. For instance, the ENS is in print
media, with both the LA Times, circulation 650,000 and the New York Post, circula-
tion 500,000:
Zitner, Adam (Los Angeles Times, May 10, 2001). Sniffing at Empty Nose Idea.
8 CHAPTER 1 Introduction and overview

“SUFFOCATING”
THE NIGHTMARE OF EMPTY NOSE SYNDROME

FIGURE 1.1
The patient stated that: “My nightmare condition makes me feel like I’m constantly
suffocating”. The story about “Empty Nose Syndrome” can be seen on YouTube: A
Condition Called Empty Nose Syndrome Left This Woman Struggling to Breathe. https://
youtu.be/QERIZS-XEC4 (71, 885 views as of October 1, 2022).

Cohen, Joyce (New York Post/Mirror.co.uk, July 15, 2018). My nightmare

condition makes me feel like I’m constantly suffocating. Fig. 1.1.
An example of a computerized tomography (CT) scan in a patient exhibiting the
common findings of the “ENS” can be seen in Fig. 1.2.

FIGURE 1.2
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is a cavernous expansion of the intranasal airway with the
absence of the lateral nasal walls and both inferior turbinates, which have been previously
surgically resected (removed-not by a Mayo Clinic surgeon) after bilateral total inferior
turbinectomies. The mucosa covering the right middle turbinate remnant is atrophic.
From: Moore EJ, Kern EB. Atrophic rhinitis: a review of 242 cases American Journal of Rhinology. 2001;15(6):
355e361. Note: we do not advocate total or subtotal turbinectomies for benign turbinate enlargement
(“hyperplastic”). (By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
 2. Empty nose syndrome (ENS) in print media, TV 9

FIGURE 1.3
From the free online encyclopedia https://en.wikipedia.org/wiki/Empty_nose_syndrome,
an example of a CT scan of an empty nose syndrome patient with “altered nasal anatomy
after bilateral subtotal inferior turbinectomy.”

Additionally, ENS is now a prominent part of the Internet lexicon. A concise discus-
sion of the “ENS” appears on the free online encyclopedia, https://www.Wikipedia.org
along with an example of a CT scan of an ENS patient with “altered nasal anatomy after
bilateral subtotal inferior turbinectomy.” Fig. 1.3 from Wikipedia. Fig. 1.4 is the CT scan
of a “normal” individual and a CT scan of an “ENS” patient seen in our practice.
If you commence a Google reference search for the ENS, you will be astonished
and overwhelmed by more than 60 citations on Google and over 60 medical refer-
ences on the PubMed database specifically with the term, ENS in the title of the
medical paper, as of November 01, 2022. Table 1.1.
Furthermore, realize that the social media platform Facebook has an Empty Nose
Syndrome Forum, while YouTube has over 40 videos with a tsunami of over 80,000
views including a segment devoted to the empty nose syndrome by the television
hostess Megyn Kelly. (Bold italics added)
Megyn Kelly On the Today Show, NBC News. August 30, 2018.
A Condition Called Empty Nose Syndrome Left This Woman Struggling to
Breathe. (Bold italics added)
https://youtu.be/QERIZS-XEC4.
(70,287 views as of August 2022)
10 CHAPTER 1 Introduction and overview

FIGURE 1.4
Coronal CT scan of a “normal” individual on the left side. Note the presence of a straight
nasal septum, normal lateral nasal walls, and both middle and inferior turbinates along
with well-aerated maxillary and ethmoid sinuses are present. On the right side is a coronal
CT scan of an “empty nose syndrome” patient exhibiting the common findings seen in
these patients. There is a cavernous expansion of the intranasal airway with the absence
of both middle and inferior turbinates that have been previously surgically resected
(removed-not by a Mayo Clinic surgeon) after a bilateral total middle and inferior
turbinectomies. The ethmoid sinuses have been partially resected, and the majority of the
lateral nasal wall is presently intact bilaterally. Note: we do not advocate total or subtotal
turbinectomies for benign turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

Oliphant J. Is the empty nose real? (Bold italics added) And if not, why are peo-
ple killing themselves over it?
BuzzFeed.com April 14, 2016.
Brett Helling a Suicide. (Bold italics added)
 2. Empty nose syndrome (ENS) in print media, TV 11

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the
title from 2001eNovember 1, 2022.
2022
1. Kanjanawasee D, Campbell RG, Rimmer J, Alvarado R, Kanjanaumporn J, Snidvongs
K, Kalish L, Harvey RJ, Sacks R. Empty nose syndrome pathophysiology: a
systematic review. Otolaryngol Head Neck Surg. 2022 Sep; 167(3):434e451. https://
doi.org/10.1177/01945998211052919. Epub 2021 Oct 19. PMID: 34665687.
2. Huang CC, Wu PW, Lee CC, Chang PH, Huang CC, Lee TJ. Suicidal thoughts in
patients with empty nose syndrome. Laryngoscope Investig Otolaryngol. 2022 Jan
19; 7(1):22e28. https://doi.org/10.1002/lio2.730. PMID: 35155779; PMCID:
PMC8823180.
3. Lamb M, Bacon DR, Zeatoun A, Onourah P, Thorp BD, Abramowitz J, Ebert CS Jr,
Kimple AJ, Senior BA. Mental health burden of empty nose syndrome compared to
chronic rhinosinusitis and chronic rhinitis. Int Forum Allergy Rhinol. 2022 Mar 25.
https://doi.org/10.1002/alr.22997. Epub ahead of print. PMID: 35333009.
4. Huang CC, Wu PW, Chuang CC, Lee CC, Lee YS, Chang PH, Fu CH, Huang CC, Lee
TJ. Identifying obstructive sleep apnoea in patients with empty nose syndrome.
Diagnostics (Basel). 2022 Jul 15; 12(7):1720. https://doi.org/10.3390/
diagnostics12071720. PMID: 35885624; PMCID: PMC9323833.
5. Hosokawa Y, Miyawaki T, Omura K, Akutsu T, Kimura R, Ikezono T, Otori N. Surgical
treatment for empty nose syndrome using autologous dermal fat: evaluation of
symptomatic improvement. Ear Nose Throat J. 2022 Sep 29:1455613221130885.
https://doi.org/10.1177/01455613221130885. Epub ahead of print. PMID:
36174975.
6. Chang MT, Bartho M, Kim D, Tsai EF, Yang A, Dholakia SS, Khanwalkar A, Rao VK,
Thamboo A, Lechner M, Nayak JV. Inferior meatus augmentation procedure (IMAP) for
treatment of empty nose syndrome. Laryngoscope. 2022 Jun; 132(6):1285e1288.
https://doi.org/10.1002/lary.30001. Epub 2022 Jan 24. PMID: 35072280.
7. Huang CC, Wu PW, Lee YS, Huang CC, Chang PH, Fu CH, Lee TJ. Impact of sleep
dysfunction on psychological burden in patients with empty nose syndrome. Int
Forum Allergy Rhinol. 2022 Jun 5. https://doi.org/10.1002/alr.23040. Epub ahead of
print. PMID: 35665478.
8. Piazza F. In reference to inferior meatus augmentation procedure (IMAP) for treatment
of empty nose syndrome. Laryngoscope. 2022 Jun; 132(6):E21. https://doi.org/10.
1002/lary.30118. Epub 2022 Apr 2. PMID: 35366012.
9. Lindemann J, Goldberg-Bockhorn E, Stupp F, Scheithauer M, Sieron HL, Hoffmann
TK, Sommer F, Zimmermann L. Erstellung einer deutschen Version des empty nose
syndrome 6 item questionnaire “(ENS6Q) [Adaption of the “Empty Nose 6 Item
Questionnaire” (ENS6Q) into German language]. Laryngorhinootologie. 2022 May 18.
German. https://doi.org/10.1055/a-1841-6542. Epub ahead of print. PMID:
35584746.
10. Chang MT, Nayak JV. In response to inferior meatus augmentation procedure (IMAP)
for treatment of empty nose syndrome. Laryngoscope. 2022 Jun; 132(6):E22.
https://doi.org/10.1002/lary.30119. Epub 2022 Apr 2. PMID: 35366011.
11. Maul X, Thamboo A. The clinical effect of psychosomatic interventions on empty
nose syndrome secondary to turbinate-sparing techniques: A prospective self-
controlled study. Int Forum Allergy Rhinol. 2021 May; 11(5):955e956. https://doi.org/
10.1002/alr.22724. Epub 2020 Nov 5. PMID: 33151623.

Continued
12 CHAPTER 1 Introduction and overview

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the title from
2001eNovember 1, 2022.dcont’d

2021
1. Law RH, Ahmed AM, Van Harn M, Craig JR. Middle turbinate resection is unlikely to
cause empty nose syndrome in first year postoperatively. Am J Otolaryngol. 2021
Jan 26; 42(4):102,931. https://doi.org/10.1016/j.amjoto.2021.102931. Epub ahead of
print. PMID: 33550027.
2. Wu CL, Fu CH, Lee TJ. Distinct histopathology characteristics in empty nose
syndrome. Laryngoscope. 2021 Jan; 131(1):E14-E18. https://doi.org/10.1002/lary.
28586. Epub 2020 Mar 3. PMID: 32125703.
3. Chang FY, Fu CH, Lee TJ. Outcomes of olfaction in patients with empty nose
syndrome after submucosal implantation. Am J Otolaryngol. 2021 Feb 18; 42(4):
102,989. https://doi.org/10.1016/j.amjoto.2021.102989. Epub ahead of print. PMID:
33676069.
4. Kim CH, Kim J, Song JA, Choi GS, Kwon JH. The degree of stress in patients with
empty nose syndrome, compared with chronic rhinosinusitis and allergic rhinitis. Ear
Nose Throat J. 2021 Feb; 100(2):NP87-NP92. https://doi.org/10.1177/
0145561319858912. Epub 2019 Jul 4. PMID: 31272211.
5. Huang CC, Wu PW, Fu CH, Huang CC, Chang PH, Lee TJ. Impact of psychologic
burden on surgical outcome in empty nose syndrome. Laryngoscope. 2021 Mar;
131(3):E694-E701. https://doi.org/10.1002/lary.28845. Epub 2020 Jul 21. PMID:
32692881.
6. Wu CL, Fu CH, Lee TJ. In response to distinct histopathology characteristics in empty
nose syndrome. Laryngoscope. 2021 Apr; 131(4):E1039. https://doi.org/10.1002/
lary.29183. Epub 2021 Jan 18. PMID: 33459370.
7. Salzano FA, Vaira LA, Maglitto F, Mesolella M, De Riu G. In reference to distinct
histopathology characteristics in empty nose syndrome. Laryngoscope. 2021 Apr;
131(4):E1038. https://doi.org/10.1002/lary.29181. Epub 2021 Jan 18. PMID:
33459372.
8. Gordiienko IM, Gubar OS, Sulik R, Kunakh T, Zlatskiy I, Zlatska A. Empty nose
syndrome pathogenesis and cell-based biotechnology products as a new option for
treatment. World J Stem Cells. 2021 26; 13(9):1293e1306. https://doi.org/10.4252/
wjsc.v13.i9.1293. PMID: 34630863; PMCID: PMC8474723.
9. La Rosa R, Passali D, Passali GC, Ciprandi G. A practical classification of the empty
nose syndrome. J Biol Regul Homeost Agents. 2021 JaneFeb; 35(1 Suppl. 2):51e54.
https://doi.org/10.23812/21-1supp2-10. PMID: 33982539.
10. Chang CF. Using platelet-rich fibrin scaffolds with diced cartilage graft in the treatment
of empty nose syndrome. Ear Nose Throat J. 2021 Sep 25:1455613211045567.
https://doi.org/10.1177/01455613211045567. Epub ahead of print. PMID:
34569297.
11. Dholakia SS, Yang A, Kim D, Borchard NA, Chang MT, Khanwalkar A, Lechner M,
Nayak JV. Long-term outcomes of inferior meatus augmentation procedure to treat
empty nose syndrome. Laryngoscope. 2,021,131(11):E2736-E2741. https://doi.
org/10.1002/lary.29593. Epub 2021 May 15. PMID: 33991117.
12. Fu CH, Chen HC, Huang CC, Chang PH, Lee TJ. Serum high-sensitivity C-reactive
protein is associated with postoperative psychiatric status in patients with empty
nose syndrome. Diagnostics (Basel). 2021 Dec 18; 11(12):2388. https://doi.org/10.
3390/diagnostics11122388. PMID: 34943627; PMCID: PMC8700485.
 2. Empty nose syndrome (ENS) in print media, TV 13

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the title from
2001eNovember 1, 2022.dcont’d
13. Amanian A, Hari K, Habib AR, Dholakia SS, Nayak J, Thamboo A. The empty nose
syndrome 6-item questionnaire (ENS6Q): a diagnostic tool to distinguish empty nose
syndrome from primary nasal obstruction. Int Forum Allergy Rhinol. 2021 Jul; 11(7):
1113e1115. https://doi.org/10.1002/alr.22761. Epub 2021 Jan 18. PMID: 33460303.
14. Tian P, Hu J, Ma Y, Zhou C, Liu X, Dang H, Zou H. The clinical effect of psychosomatic
interventions on empty nose syndrome secondary to turbinate-sparing techniques:
a prospective self-controlled study. Int Forum Allergy Rhinol. 2021 Jun; 11(6):984e992.
https://doi.org/10.1002/alr.22726. Epub 2020 Nov 5. PMID: 33151634.
15. Maul X, Thamboo A. The clinical effect of psychosomatic interventions on empty
nose syndrome secondary to turbinate-sparing techniques: A prospective self-
controlled study. Int Forum Allergy Rhinol. 2021 May; 11(5):955e956. https://doi.org/
10.1002/alr.22724. Epub 2020 Nov 5. PMID: 33151623.
16. Malik J, Dholakia S, Spector BM, Yang A, Kim D, Borchard NA, Thamboo A, Zhao K,
Nayak JV. Inferior meatus augmentation procedure (IMAP) normalizes nasal airflow
patterns in empty nose syndrome patients via computational fluid dynamics (CFD)
modeling. Int Forum Allergy Rhinol. 2021 May; 11(5):902e909. https://doi.org/10.
1002/alr.22720. Epub 2020 Nov 29. PMID: 33249769; PMCID: PMC8062271.
17. Hassan CH, Malheiro E, Béquignon E, Coste A, Bartier S. Sublabial bioactive glass
implantation for the management of primary atrophic rhinitis and empty nose
syndrome: operative technique. Laryngoscope Investig Otolaryngol. 2021 Dec 8;
7(1):6e11. https://doi.org/10.1002/lio2.713. PMID: 35155777; PMCID:
PMC8823167.
2020
1. Gill AS, Said M, Tollefson TT, Strong EB, Nayak JV, Steele TO. Patient-reported
outcome measures and provocative testing in the workup of empty nose syndrome-
advances in diagnosis: a systematic review. Am J Rhinol Allergy. 2020 Jan; 34(1):134e140.
https://doi.org/10.1177/1945892419880642. Epub 2019 Oct 8. PMID: 31594386.
2. Tranchito E, Chhabra N. Rhinotillexomania manifesting as empty nose syndrome.
Ann Otol Rhinol Laryngol. 2020 Jan; 129(1):87e90. https://doi.org/10.1177/
0003489419870832. Epub 2019 Aug 16. PMID: 31416334.
3. Patel P, Most SP. Functionally crippled nose. Facial Plast Surg. 2020 Feb; 36(1):66e71.
doi:10.55/s-0040-1701488. Epub 2020 Mar 19. PMID: 32191961. (Bold italics ours)
Note: This paper is one of 3 exceptions but is included in this Table 1 since the authors
stated: “A variety of surgical interventions can also result in a functionally crippled nose
and diagnoses including nasal valve stenosis, septal perforations, and empty nose
syndrome are discussed.”
4. Le Bon SD, Horoi M, Le Bon O, Hassid S. Intranasal trigeminal training in empty nose
syndrome: a pilot study on 14 patients. Clin Otolaryngol. 2020 Mar; 45(2):259e263.
https://doi.org/10.1111/coa.13483. Epub 2019 Dec 11. PMID:31777150.
5. Thamboo A, Dholakia SS, Borchard NA, Patel VS, Tangbumrungtham N, Velasquez N,
Huang Z, Zarabanda D, Nakayama T, Nayak JV. Inferior meatus augmentation
procedure (IMAP) to treat empty nose syndrome: a pilot study. Otolaryngol Head
Neck Surg. 2020 Mar; 162(3):382e385. https://doi.org/10.1177/0194599819900263.
Epub 2020 Jan 14. PMID: 31935161.

Continued
14 CHAPTER 1 Introduction and overview

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the title from
2001eNovember 1, 2022.dcont’d
6. Malik J, Thamboo A, Dholakia S, Borchard NA, McGhee S, Li C, Zhao K, Nayak JV. The
cotton test redistributes nasal airflow in patients with empty nose syndrome. Int
Forum Allergy Rhinol. 2020 Apr; 10(4):539e545. https://doi.org/10.1002/alr.22489.
Epub 2020 Jan 17. PMID: 31951101; PMCID: PMC7182493.
7. Malik J, Dholakia S, Spector BM, Yang A, Kim D, Borchard NA, Thamboo A, Zhao K,
Nayak JV. Inferior meatus augmentation procedure (IMAP) normalizes nasal airflow
patterns in empty nose syndrome patients via computational fluid dynamics (CFD)
modeling. Int Forum Allergy Rhinol. 2020 Nov 29. https://doi.org/10.1002/alr.22720.
Epub ahead of print. PMID: 33249769.
8. Maul X, Thamboo A. The clinical effect of psychosomatic interventions on empty nose
syndrome secondary to turbinate-sparing techniques: A prospective self- controlled
study. Int Forum Allergy Rhinol. 2020 Nov 5. https://doi.org/10.1002/alr.22724. Epub
ahead of print. PMID: 33151623.
9. Tian P, Hu J, Ma Y, Zhou C, Liu X, Dang H, Zou H. The clinical effect of psychosomatic
interventions on empty nose syndrome secondary to turbinate-sparing techniques: a
prospective self-controlled study. Int Forum Allergy Rhinol. 2020 Nov 5. https://doi.org/
10.1002/alr.22726. Epub ahead of print. PMID: 33151634.
2019
1. Maza G, Li C, Krebs JP, Otto BA, Farag AA, Carrau RL, Zhao K. Computational fluid
dynamics after endoscopic endonasal skull base surgery-possible empty nose
syndrome in the context of middle turbinate resection. Int Forum Allergy Rhinol. 2019
Feb; 9(2):204e211. https://doi.org/10.1002/alr.22236. Epub 2018 Nov 29. PMID:
30488577; PMCID: PMC6358472.
2. Alnæs M, Andreassen BS. Osteomyelitis after radiofrequency turbinoplasty. Tidsskr nor
Laegeforen. 2019 May 16; 139(9). Norwegian, English. https://doi.org/10.4045/tidsskr.
18.0843. PMID: 31140260. Note: One patient developed “empty nose syndrome”
3. Borchard NA, Dholakia SS, Yan CH, Zarabanda D, Thamboo A, Nayak JV. Use of intranasal
submucosal fillers as a transient implant to alter upper airway aerodynamics: implications for
the assessment of empty nose syndrome. Int Forum Allergy Rhinol. 2019 Jun; 9(6):681
e687. https://doi.org/10.1002/alr.22299. Epub 2019 Feb 4. PMID: 30715801.
4. Manji J, Patel VS, Nayak JV, Thamboo A. Environmental triggers associated with
empty nose syndrome symptoms: a cross-sectional study. Ann Otol Rhinol Laryngol.
2019 Jul; 128(7):601e607. https://doi.org/10.1177/0003489419833714. Epub 2019
Feb 28. PMID: 30818962.
5. Gill AS, Said M, Tollefson TT, Steele TO. Update on empty nose syndrome: disease
mechanisms, diagnostic tools, and treatment strategies. Curr Opin Otolaryngol Head
Neck Surg. 2019 Aug; 27(4):237e242. https://doi.org/10.1097/MOO.
0000000000000544. PMID: 31116142.
6. Fu CH, Wu CL, Huang CC, Chang PH, Chen YW, Lee TJ. Nasal nitric oxide in relation to
psychiatric status of patients with empty nose syndrome. Nitric Oxide. 2019 Nov 1;
92:55e59. https://doi.org/10.1016/j.niox.2019.07.005. Epub 10. PMID: 31408674.
7. Talmadge J, Nayak JV, Yao W, Citardi MJ. Management of postsurgical empty nose
syndrome. Facial Plast Surg Clin North Am. 2019 Nov; 27 (4):465e475. https://doi.
org/10.1016/j.fsc.2019.07.005. PMID: 31587766.
8. Huang CC, Wu PW, Fu CH, Huang CC, Chang PH, Wu CL, Lee TJ. What drives depression
in empty nose syndrome? a sinonasal outcome test-25 subdomain analysis. Rhinology.
2019 Dec 1; 57(6):469e476. https://doi.org/10.4193/Rhin19.085. PMID: 31502597.
 2. Empty nose syndrome (ENS) in print media, TV 15

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the title from
2001eNovember 1, 2022.dcont’d

2018
1. Li C, Farag AA, Maza G, McGhee S, Ciccone MA, Deshpande B, Pribitkin EA, Otto BA,
Zhao K. Investigation of the abnormal nasal aerodynamics and trigeminal functions
among empty nose syndrome patients. Int Forum Allergy Rhinol. 2018 Mar; 8(3):
444e452. https://doi.org/10.1002/alr.22045. Epub 2017 Nov 22. PMID: 29165896;
PMCID: PMC6015742.
2. Lee TJ, Fu CH, Wu CL, Lee YC, Huang CC, Chang PH, Chen YW, Tseng HJ. Surgical
outcome for empty nose syndrome: impact of implantation site. Laryngoscope. 2018
Mar; 128(3):554e559. https://doi.org/10.1002/lary.26769. Epub 2017 Jul 17. PMID:
28714537.
3. Tan NC, Goggin R, Psaltis AJ, Wormald PJ. Partial resection of the middle turbinate
during endoscopic sinus surgery for chronic rhinosinusitis does not lead to an increased
risk of empty nose syndrome: a cohort study of a tertiary practice. Int Forum Allergy
Rhinol. 2018 Apr 6. https://doi.org/10.1002/alr.22127. Epub ahead of print. PMID:
29633570.
4. Dzhenkov DL, Stoyanov GS, Georgiev R, Sapundzhiev N. Histopathological findings in
an unclassifiable case of empty nose syndrome with long-term follow-up. Cureus.
2018 May 20; 10(5):e2655. https://doi.org/10.7759/cureus.2655. PMID: 30042906;
PMCID: PMC6054367.
5. Manji J, Nayak JV, Thamboo A. The functional and psychological burden of empty
nose syndrome. Int Forum Allergy Rhinol. 2018 Jun; 8(6):707e712. https://doi.org/10.
1002/alr.22097. Epub 2018 Feb 14. PMID: 29443458.
6. Kim DY, Hong HR, Choi EW, Yoon SW, Jang YJ. Efficacy and safety of autologous
stromal vascular fraction in the treatment of empty nose syndrome. Clin Exp
Otorhinolaryngol. 2018 Dec; 11(4):281e287. https://doi.org/10.21053/ceo.2017.
01634. Epub 2018 May 16. PMID: 29764011; PMCID: PMC6222192.
2017
1. Velasquez N, Thamboo A, Habib AR, Huang Z, Nayak JV. The empty nose syndrome
6-item questionnaire (ENS6Q): a validated 6-item questionnaire as a diagnostic aid for
empty nose syndrome patients. Int Forum Allergy Rhinol. 2017 Jan; 7(1):64e71.
https://doi.org/10.1002/alr.21842. Epub 2016 Aug 24. PMID: 27557473.
2. Konstantinidis I, Tsakiropoulou E, Chatziavramidis A, Ikonomidis C, Markou K.
Intranasal trigeminal function in patients with empty nose syndrome. Laryngoscope.
2017 Jun; 127(6):1263e1267. https://doi.org/10.1002/lary.26491. Epub 2017 Feb 22.
PMID: 28224626.
3. Li C, Farag AA, Leach J, Deshpande B, Jacobowitz A, Kim K, Otto BA, Zhao K.
Computational fluid dynamics and trigeminal sensory examinations of empty nose
syndrome patients. Laryngoscope. 2017 Jun; 127(6):E176-E184. https://doi.org/10.
1002/lary.26530. Epub 2017 Mar 9. PMID: 28278356; PMCID: PMC5445013.
4. Thamboo A, Velasquez N, Habib AR, Zarabanda D, Paknezhad H, Nayak JV. Defining
surgical criteria for empty nose syndrome: Validation of the office-based cotton test
and clinical interpretability of the validated empty nose syndrome 6-item
questionnaire. Laryngoscope. 2017 Aug; 127(8):1746e1752. https://doi.org/10.1002/
lary.26549. Epub 2017 Mar 27. PMID: 28349563.

Continued
16 CHAPTER 1 Introduction and overview

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the title from
2001eNovember 1, 2022.dcont’d
5. Mangin D, Bequignon E, Zerah-Lancner F, Isabey D, Louis B, Adnot S, Papon JF,
Coste A, Boyer L, Devars du Mayne M. Investigating hyperventilation syndrome in
patients suffering from empty nose syndrome. Laryngoscope. 2017 Sep; 127(9):1983
e88. https://doi.org/10.1002/lary.26599. Epub 2017 Apr 13. PMID: 28407251.
6. Balakin BV, Farbu E, Kosinski P. Aerodynamic evaluation of the empty nose
syndrome by means of computational fluid dynamics. Comput Methods Biomech
Biomed Engin. 2017 Nov; 20(14):1554e1561. https://doi.org/10.1080/10255842.
2017.1385779. Epub 2017 Oct 24. PMID: 29064287.
7. Ma ZX, Quan-Zeng, Jie-Liu, Hu GH. Assessment of postsurgical outcomes between
different implants in patients with empty nose syndrome: a meta-analysis. J Int Med
Res. 2017 Dec; 45(6):1939e1948. https://doi.org/10.1177/0300060517715167. Epub
2017 Nov 3. PMID: 29098901; PMCID: PMC5805217.
2016
1. Hong HR, Jang YJ. Correlation between remnant inferior turbinate volume and
symptom severity of empty nose syndrome. Laryngoscope. 2016 Jun; 126(6):
1290e1295. https://doi.org/10.1002/lary.25830. Epub 2015 Dec 21. PMID: 26692010.
2. Lee TJ, Fu CH, Wu CL, Tam YY, Huang CC, Chang PH, Chen YW, Wu MH. Evaluation
of depression and anxiety in empty nose syndrome after surgical treatment.
Laryngoscope. 2016 Jun; 126(6):1284e1289. https://doi.org/10.1002/lary.25814.
Epub2015 Dec 15. PMID: 26667794.
3. Shah K, Guarderas J, Krishnaswamy G. Empty nose syndrome and atrophic rhinitis.
Ann Allergy Asthma Immunol. 2016 Sep; 117(3):217e220. https://doi.org/10.1016/j.
anai.2016.07.006. PMID: 27613452.
4. Thamboo A, Velasquez N, Ayoub N, Nayak JV. Distinguishing computed tomography
findings in patients with empty nose syndrome. Int Forum Allergy Rhinol. 2016 Oct;
6(10):1075e1082. https://doi.org/10.1002/alr.21774. Epub 2016 Jul 13. PMID:
27409044.
2015
1. Sozansky J, Houser SM. Pathophysiology of empty nose syndrome. Laryngoscope.
2015 Jan; 125(1):70e74. https://doi.org/10.1002/lary.24813. Epub 2014 Jun 30.
PMID: 24978195.
2. Kuan EC, Suh JD, Wang MB. Empty nose syndrome. Curr Allergy Asthma Rep. 2015
Jan; 15(1):493. https://doi.org/10.1007/s11882-014-0493-x. PMID: 25430954.
3. Lemogne C, Consoli SM, Limosin F, Bonfils P. Treating empty nose syndrome as a
somatic symptom disorder. Gen Hosp Psychiatry. 2015 MayeJun; 37(3):273.e9e10.
https://doi.org/10.1016/j.genhosppsych.2015.02.005. Epub 2015 Feb 25. PMID:
25754986.
4. Leong SC. The clinical efficacy of surgical interventions for empty nose syndrome: a
systematic review. Laryngoscope. 2015 Jul; 125(7):1557e1562. https://doi.org/10.
1002/lary.25170. Epub 2015 Feb 3. PMID: 25647010.
5. Chang AA, Watson D. Inferior turbinate augmentation with auricular cartilage for the
treatment of empty nose syndrome. Ear Nose Throat J. 2015 OcteNov; 94(10e11):
E14eE15. PMID: 26535824.
 2. Empty nose syndrome (ENS) in print media, TV 17

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the title from
2001eNovember 1, 2022.dcont’d
6. Velasquez N, Huang Z, Humphreys IM, Nayak JV. Inferior turbinate reconstruction
using porcine small intestine submucosal xenograft demonstrates improved quality of
life outcomes in patients with empty nose syndrome. Int Forum Allergy Rhinol. 2015
Nov; 5(11):1077e1081. https://doi.org/10.1002/alr.21633. Epub 2015 Sep 2. PMID:
26332403.
2014
1. Tam YY, Lee TJ, Wu CC, Chang PH, Chen YW, Fu CH, Huang CC. Clinical analysis of
submucosal medpor implantation for empty nose syndrome. Rhinology. 2014 Mar;
52(1):35e40. https://doi.org/10.4193/Rhin13.086. PMID: 24618626.
2. Jiang C, Wong F, Chen K, Shi R. Assessment of surgical results in patients with empty
nose syndrome using the 25-item sino-nasal outcome test evaluation. JAMA
Otolaryngol Head Neck Surg. 2014 May; 140(5):453e458. https://doi.org/10.1001/
jamaoto.2014.84. PMID: 24626391.
2013
1. Saafan ME. Acellular dermal (alloderm) grafts versus silastic sheets implants for
management of empty nose syndrome. Eur Arch Otorhinolaryngol. 2013 Feb; 270(2):
527e533. doi:10.1007/s00405-012-1955-1. Epub 2012 Apr 19. PMID: 22526572.
2. Bastier PL, Bennani-Baiti AA, Stoll D, de Gabory L. b-Tricalcium phosphate implant to
repair empty nose syndrome: preliminary results. Otolaryngol Head Neck Surg. 2013
Mar; 148(3):519e522. https://doi.org/10.1177/0194599812472436. Epub 2013 Jan 8.
PMID: 23300225.
3. Jiang C, Shi R, Sun Y. Study of inferior turbinate reconstruction with Medpor for the
treatment of empty nose syndrome. Laryngoscope. 2013 May; 123(5):1106e1111.
https://doi.org/10.1002/lary.23908. Epub 2012 Dec 3. PMID: 23208803.
4. Jung JH, Baguindali MA, Park JT, Jang YJ. Costal cartilage is a superior implant
material than conchal cartilage in the treatment of empty nose syndrome. Otolaryngol
Head Neck Surg. 2013 Sep; 149(3):500e5005. https://doi.org/10.1177/
0194599813491223. Epub 2013 May 31. PMID: 23728068.
5. Di MY, Jiang Z, Gao ZQ, Li Z, An YR, Lv W. Numerical simulation of airflow fields in two
typical nasal structures of empty nose syndrome: a computational fluid dynamics
study. PLoS One. 2013 Dec 18; 8(12):e84243. https://doi.org/10.1371/journal.pone.
0084243. PMID: 24367645; PMCID: PMC3867489.
2012
1. Coste A, Dessi P, Serrano E. Empty nose syndrome. Eur Ann Otorhinolaryngol Head
Neck Dis. 2012 Apr; 129(2):93e97. https://doi.org/10.1016/j.anorl.2012.02.001. Epub
2012 Apr 16. PMID: 22513047.
2. Di MY, Gao ZQ, Lü W. [Research progress in empty nose syndrome]. Zhonghua Er Bi
Yan Hou Tou Jing Wai Ke Za Zhi. 2012 Oct; 47(10):873e876. Chinese. PMID:
23302177.

Continued
18 CHAPTER 1 Introduction and overview

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the title from
2001eNovember 1, 2022.dcont’d

2011
1. Hildenbrand T, Weber RK, Brehmer D. Rhinitis sicca, dry nose and atrophic rhinitis: a
review of the literature. Eur Arch Otorhinolaryngol. 2011 Jan; 268(1):17e26. doi:
10.1007/s00405-010-1391-z. Epub 2010 Sep 29. PMID: 20878413. Note: This is the
2nd of 3 exceptions but since in this abstract it is stated as follows: “Since the uncritical
resection of the nasal turbinates is a significant and frequent factor in the genesis of dry
nose, secondary RA and ENS (empty nose syndrome) (definition of abbreviation of
ENS added), the inferior and middle turbinate should not be resected without adequate
justification, and the simultaneous removal of both should not be done other than for a
malignant condition.”
2. Modrzyn ski M. Hyaluronic acid gel in the treatment of empty nose syndrome. Am J
Rhinol Allergy. 2011 MareApr; 25(2):103e106. https://doi.org/10.2500/ajra.2011.25.
3577. PMID: 21679513.
3. Jang YJ, Kim JH, Song HY. Empty nose syndrome: radiologic findings and treatment
outcomes of endonasal microplasty using cartilage implants. Laryngoscope. 2011 Jun;
121(6):1308e1312. https://doi.org/10.1002/lary.21734. Epub 2011 May 6. PMID:
21557228.
4. Freund W, Wunderlich AP, Stöcker T, Schmitz BL, Scheithauer MO. Empty nose
syndrome: limbic system activation observed by functional magnetic resonance
imaging. Laryngoscope. 2011 Sep; 121(9):2019e2025. https://doi.org/10.1002/lary.
21903. Epub 2011 Aug 16. PMID: 22024858.
2010
1. Scheithauer MO. Nasenmuschelchirurgie and “Empty Nose” Syndrome [Surgery of the
turbinates and “empty nose” syndrome]. Laryngorhinootologie. 2010 May; 89 Suppl 1:
S79eS102. German. https://doi.org/10.1055/s-0029-1246126. Epub 2010 Mar 29.
PMID: 20352572.
2. Scheithauer MO. Surgery of the turbinates and “empty nose” syndrome. GMS Curr Top
Otorhinolaryngol Head Neck Surg. 2010; 9:Doc03. https://doi.org/10.3205/cto000067.
Epub 2011 Apr 27. PMID: 22073107; PMCID: PMC3199827.
2009
1. Chhabra N, Houser SM. The diagnosis and management of empty nose syndrome.
Otolaryngol Clin North Am. 2009 Apr; 42(2):311e330, ix. https://doi.org/10.1016/j.otc.
2009.02.001. PMID: 19328895.
2. Payne SC. Empty nose syndrome: What are we really talking about? Otolaryngol Clin
North Am. 2009 Apr; 42(2):331e337, ix-x. https://doi.org/10.1016/j.otc.2009.02.002.
PMID: 19328896
2008 No papers
2007
1. Houser SM. Surgical treatment for empty nose syndrome. Arch Otolaryngol Head
Neck Surg. 2007 Sep; 133(9):858e863. https://doi.org/10.1001/archotol.133.9.858.
PMID: 17875850.
 2. Empty nose syndrome (ENS) in print media, TV 19

Table 1.1 PubMed database references: Empty nose syndrome (ENS) in the title from
2001eNovember 1, 2022.dcont’d

2006
1. Houser SM. Empty nose syndrome associated with middle turbinate resection.
Otolaryngol Head Neck Surg. 2006 Dec; 135(6):972e973. https://doi.org/10.1016/j.
otohns.2005.04.017. PMID: 17141099.
2002e05 No papers
2001
1. Wang Y, Liu T, Qu Y, Dong Z, Yang Z. [Empty nose syndrome]. Zhonghua Er Bi Yan
Hou KeZa Zhi. 2001 Jun; 36(3):203e205. Chinese. PMID: 12761925.
2. Moore EJ, Kern EB. Atrophic rhinitis: a review of 242 cases. Am J Rhinol. 2001 Nov
eDec; 15(6):355e361. PMID: 11777241 Note: this paper is the 3rd of 3 exceptions but
is included because, to our knowledge, this is the first presentation of the term “empty
nose syndrome” in the written medical literature.

Abstracted from the story: “Turbinate reductions are routinely performed around
the world, and usually with great success. But some patients say this surgical proced-
ure ruined their lives”. In Michael Jackson’s wrongful death suit, one of his doctors
testified that Jackson’s insomnia could have been a result of empty nose syndrome.
Online ENS forums and Facebook support groups are filled with people who say
they’ve been discarded by doctors who told them nothing is wrongdthat it’s psycho-
genic, all in their heads. In China, one man who said he had empty nose syndrome
became so enraged that he stabbed an otolaryngologist to death. Others direct
violence toward themselves. When regular ENS commenters go silent online, the
community wonders if they’re gone for good.
Harmon T. Medical Mystery: Empty Nose Syndrome: (Bold italics added)
CBS News. Aug 30, 2016
https://youtu.be/8Ue4SZihtM4.
(4062 views as of August 2022)
The Medical Science Behind Empty Nose Syndrome. (Bold italics added)
December 16, 2018. https://youtu.be/C50JWQkXr3s (9035 views as of August
2022).
ENS Victim Scott Gaffer’s Story-a Suicide. (Bold italics added) January 30,
2019.
https://youtu.be/U5h9URck708 (17,249 views as of August 2022)
ENS Victim Dory’s Story-a Suicide. (Bold italics added) March 14, 2020.
https://youtu.be/073TilZvc40 (10,325 views as of August 2022)
Empty Nose Treatment at Stanford University. October 24, 2020.
https://youtu.be/pK361MrCYUwdo897.
(3100 views as of March 2023)
The horrifying report of the murder of an ENT surgeon by a patient: Newsday,
BBC News. April 6, 2014.
20 CHAPTER 1 Introduction and overview

China sees a wave of violence against staffdEmpty Nose Syndrome casedENT

doctor murdered.
https://youtu.be/ikFlH4CallHerTheOhqbo7o.
(1921 views as of March 2021) (Blue type from original citation and bold italics
added)
Note: as of August 2022, when attempting to access this site and the message
delivered was: “this video isn’t available anymore.”
Moreover, the Internet is flooded with numerous patient posts regarding their
ENS symptoms along with information and support websites for the “postnasal sur-
gery dysfunction community” including:
https//www.change.org/emptynose
https://www.usasinus.org/empty-nose-syndrome
https://www.nasalcripple.com.
Some other terms and sites acquired from https://www.nasalcripple.com are:

The ENS is an existent authentic reality; it is no longer debatable and it may be

more common than the obscure rarity some authors claim.
In 2020, on the American Rhinologic Society website, the following quotation
appeared:
“The exact incidence of ENS is currently unknown. There are still thousands of
patients experiencing ENS.”
Yes, ENS patients exist. They are enormously exasperated and often feel
betrayed by their surgeon since, by definition, ENS is an iatrogenic syndrome, a sec-
ondary atrophic rhinitis, consequent to “aggressive” surgical trauma to their turbi-
nates although denied, refuted, and rejected by some surgeons. The turbinate
 3. Nasal physiology 21

trauma is generally focused and targeted to the inferior turbinate(s), but not
excluding the middle turbinate(s). ENS is meaningful because patients are so miser-
able physically and so distraught emotionally that tangible acknowledgment by the
profession is both consequential and pressing.
Pressing because even today, in the current “enlightened” medical era, patients
with ENS are still encountered worldwide, supported by the web sites above,
because some surgeons deny the contributing, causative relationship between turbi-
nate trauma and the symptom complex known as ENS. Although exact numbers are
unobtainable, nasal operative procedures are carried out today, in the first quarter of
the 21st century, in vast numbers,* annually, in the United States of America, as
there are over a half a million (500,000) nasal operations, some of which may still
result in ENS; therefore, there needs to be a moratorium on the “aggressive” attacks
against the nasal turbinates mandating replacement by more conservative turbinate
procedures for physiologic reasons and ultimately for the welfare of the patients in
our trust.
*Between Plastic Surgery.org and the National Library of Medicine website com-
bined, there are approximately 500,000 to 600,000 nasal septal and cosmetic nasal
surgical operations performed annually in the United States of America.

3. Nasal physiology: olfaction, breathing (“perfect nasal

resistance”), internal nasal valve area, defensive
immunoglobulins, cytokines plus T and B lymphocytes
While nasal physiology broadly includes olfaction, it is the primary nasal functions
of breathing (respiration) and defense that are wholly wounded leading to the symp-
toms of ENS. Regarding the major nasal function of breathing, it is important to
recognize that the nose is the first portion of the entire respiratory system, which af-
fords an essential and critical upper airway resistance, provided by the internal
nasal valve area, which contains the head of the inferior turbinate. Figs. 1.5, 1.6,
1.7 and 1.8.
The internal nasal valve is a three-dimensional structure that includes the head of
the inferior turbinate. The other structures composing the internal nasal valve area in
addition to the head of the inferior turbinate include the caudal end of the upper
lateral cartilage, the nasal septum, and the floor of the pyriform aperture with its
mucocutaneous coverings.
This anatomic fact and physiologic conception, of the internal nasal valve as a
three-dimensional structure, was announced by the exceptional research of Haight
and Cole from the University of Toronto, Canada, over 35 years ago in 1983.5
This contribution was sustained and verified by the application of this anatomic
and functional certainty through the clinical work of surgeons from the Mayo Clinic
in 1987,6 although the awareness of a nasal valve as an anatomic reality was first
22 CHAPTER 1 Introduction and overview

FIGURE 1.5
Uninstrumented base view of the left nostril of a female with a normal nose and a normal
“internal nasal valve angle” is easily seen.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 1.6
Photograph is an uninstrumented clinical view of the left side of a female with a normal
nose. Many structures of the internal and external nasal valve (lower lateral cartilage and
ala) are seen and labeled; the head of the inferior turbinate is part of the internal nasal
valve area.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
 3. Nasal physiology 23

FIGURE 1.7
The lower left illustration reveals the clinical internal nasal valve angle. In the upper right
corner of the illustration is the representative conception of the total internal nasal valve
area (shaded area). The concept of the entire internal nasal valve area was presented to
the profession and verified by Haight and Cole in 1983.5 The total internal nasal valve area
includes the upper lateral cartilage (ULC), the septal cartilage (the septal turbinate “swell
body” not shown), the floor of the nose, the piriform aperture, the frontal (ascending)
process of the maxilla, and the head of the inferior turbinate. The internal nasal valve
angle is represented as ranging from 10 to 15 degrees, although some other authors have
different findings.
Structures of the internal nasal valve area include:
1. Nasal septum (including the premaxillary wings)
2. Upper lateral cartilage (ULC)
3. Piriform aperture
4. Fibroareolar lateral soft tissues
5. Frontal (ascending) process of the maxilla
6. Head of the inferior turbinate
7. Mucosal and cutaneous (skin) “mucocutaneous” coverings of these structures
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
24 CHAPTER 1 Introduction and overview

FIGURE 1.8
This illustration depicts the internal nasal valve area (visualized) as an inverted three-
dimensional cone-shaped area. The triangular portion (apex of the cone) fits into the apex
of the nasal valve angle, between the nasal septum in the upper lateral cartilage (ULC).
The base of the cone fits into a broader area including the floor of the nose (floor of the
piriform aperture) and is bounded by the head of the inferior turbinate posteriorly, the
premaxillary wing region of the nasal septum medially, and the frontal (ascending)
process of the maxilla laterally.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

introduced to the literature more than 100 years ago by the anatomist PJ Mink from
Utrecht in the Netherlands.7,8
We ask you, the reader, the following question, in your personal experience, what
is more satisfying, mouth breathing or breathing through your nose (nasal
breathing)?
Nasal breathing accounts for approximately 60%e70% of the total respiratory
tract resistance and is a higher resistance system than mouth breathing; yet, from
our personal experience and according to most patients, nasal breathing is much
more satisfying than mouth (lower resistance) breathing.22
 3. Nasal physiology 25

A specific “perfect nasal resistance” is required for producing the ideal intratho-
racic negative pressure gradient, which in turn creates the optimal opening of the pe-
ripheral bronchioles enhancing alveolar ventilation, facilitating oxygen and carbon
dioxide exchange. Respiration is, after all, the exchange of oxygen and carbon diox-
ide at the alveolar level. This situation of ideal intrathoracic negative pressure which
expedites pulmonary and cardiac venous blood flow return is seriously altered if the
head of the inferior turbinate is resected nosediving nasal airway resistance.
Normal nasal airway resistance is essential not only for normal nasal function but
also additionally is requisite for optimal and peak pulmonary physiology during both
inspiration and during expiration. This fact has been realized by some Italian nasal
surgeons for more than a quarter of a century.9 As has been recently pointed out by
Balakin et al.10 in 2017, understanding nasal airway resistance is crucial as they
stated that, “The reduction of aerodynamic resistance observed in the postoperative
case may result in disruption of pulmonary functions”, as it follows from both
Ramadan et al. 198411; and Flanagan and Eccles 1997.12 Lung hyperventilation
may occur in the event breathing depth remains constant, an observation confirmed
in literature by Mangin et al.in 2014.13 Studying nasal aerodynamics by means of
computational fluid dynamics (CFD) to understand the ENS symptom of ‘paradox-
ical nasal obstruction’, Balakin et al.10 proposed that a reduction in nasal airflow
resistance can modify nasal aerodynamics affecting lung function. “The potential
outcome could be changes in the microclimate and sensation and thereby alter the
pulmonary function.”10 In a study of lung volumes and arterial oxygenation pub-
lished in the journal The Lancet by Swift and colleagues, using nasal pack occlusion,
found that total lung capacity, functional residual capacity, and residual volume
decreased significantly, which is the equivalent of mouth breathing. All three vol-
umes increased back to normal when nasal breathing resumed.14 Therefore, lung
volumes are increased back to normal when there is a total increase in airway resis-
tance back to normal. In addition, lung volumes are reduced or decreased when there
is a total decrease in nasal airway resistance, as in ENS or mouth breathing.
“These findings imply that the resistance to expiration provided by the nose helps
maintain lung volumes and so may indirectly determine arterial oxygenation.”14
After passing through the internal nasal valve, the inspired air exhibits the
designed turbulent air flow, which heightens intimate contact between the air stream
and the nasal mucosa maximizing both heating and moisturizing of the inspired air
providing proper warmth and humidity for the flawless exchange of oxygen and car-
bon dioxide at the alveolar level.
The nasal mucosa is also responsible for significant protective defensive func-
tions, which are mechanical, humoral, cellular plus nasal reflexes. The three primary
functions of the nose are summarized in Table 1.2. For example, first the vibrissae at
26 CHAPTER 1 Introduction and overview

Table 1.2 Three primary functions of the nose.

1. OlfactiondIs one of the oldest senses and a component of the defensive system as it
provides the organism with odorant identification receptors able to recognize food,
prospective mating partners, and possible enemies and other dangers. 34,35
2. Breathing (respiration)dRegarding the major nasal function of breathing, it is
important to recognize that the nose is the first portion of the entire respiratory system,
which affords an essential and critical upper airway resistance, provided by the internal
nasal valve area which contains the head of the inferior turbinate. The nose creates the
proper resistance (‘resistor function’dthe internal nasal valve area) for breathing;
lung expansion, enhancing venous return, charging the inspired air (‘diffusor
function’dturbulent air flow) with warmth (temperature) and moisture (humidity),
enabling idea CO2 and O2 exchange to occur optimally at the alveolar level, which is, after
all, respiration.26 The trigeminal nerve mediates the perception of normal nasal airflow by
action potentials from the transient receptor potentials melastatin 8 (TRPM8) receptors
which are located in the mucosa, goblet cells and vessels, not in the connective tissues.
These TRPM8 receptors, the trigeminal “cool” thermoreceptors, are triggered by the wall
shearing effects of the inspired air currents cooling the nasal mucosa providing the sense
of normal breathing.33,74,358e360
3. DefensedThe nasal mucosa and submucosa (lamina propria, stroma) have four
separate defensive systems including: mechanical, humoral, cellular, and various nasal
reflex defenses.4
A. The mechanical defenses include vibrissae, the mucus blanket, and the epithelial lining
itself.
Nasal cleansing occurs by filtering particles from the inspiratory air by capturing and
clearing those particulate particles that precipitate onto the mucosa and removed by
ciliary activity. The mucus itself it is composed of a superficial gel layer for trapping
foreign particles and a deeper liquid layer that facilitates ciliary motility. Mucociliary
transport (MCT) occurs at a rate of 1e2 cm/minute and can be measured using the
saccharine test.4
B. The humoral defense system centers around the immunoglobulins IgA and IgG. IgM
also appears in the nasal secretions but at very low levels. All these immunoglobulins
are produced in the nasal mucosa by plasma cells and B lymphocytes. Other cells
involved in the humoral defense system include histamine, leukotrienes, and
prostaglandins. The interleukins (Ils) (a group of cytokines produced in the nasal
mucosa) are released during inflammatory events such as rhinitis and rhinosinusitis.
These cytokines are released by numerous cells including leukocytes, neutrophils,
eosinophils, and fibroblasts. The most important Ils include Il-4, Il-5, Il-8, and Il-13. Also
included are the antimicrobial secretory proteins lactoferrin (Lf), lysozyme (Ly), and
human beta-defensin 1 (hBD-1).4,15e17
C. The cellular defensive system is a vibrant system living and breathing in the
neurovascular bundles located in nasal submucosa (lamina propria, stroma) including
the dendritic cells that present foreign proteins to T and B lymphocytes to initiate
immune responses. Supplementing the T and B lymphocytes other specific defensive
cells include eosinophils, mast cells, basophils, and plasma cells.4
 3. Nasal physiology 27

Table 1.2 Three primary functions of the nose.dcont’d

D. The nasal reflex system of defense includes the sneeze and the nasal pulmonary reflex
which may induce apnea with laryngeal and bronchial construction as a means of
protecting the lower airway. Other lesser-known reflexes that may be protective and
defensive include: the diving reflex (apnea and bradycardia), nasocardiac reflex
(bradycardia and hypotension), nasovascular reflex (peripheral vasoconstriction) all of
which may occur secondary to robust nasal mucosal stimulation secondary nasal
tracheal intubation. Lastly there appears to be a genitonasal reflex (obstructive swelling
of the nasal mucosa during sexual arousal producing a type of “honeymoon rhinitis”).4
In summary: Regarding the major nasal function of breathing, the nose is the first portion of
the entire respiratory system, which affords an essential and critical upper airway
resistance, provided by the internal nasal valve area which contains the head of the
inferior turbinate. The nasal mucosa and submucosa (lamina propria, stroma) have both
humoral and cellular defensive capabilities, and some of defensive functions include
olfaction, nasal reflexes including the sneeze, nasopulmonary, nasocardiac and diving
reflexes, the vibrissae, mucociliary transport, nitrous oxide, secretory proteins including the
antimicrobial proteins lactoferrin (Lf), lysozyme (Ly), and human beta-defensin 1 (hBD-1).
Other defensive components include secretory IgA, IgG, leukotrienes, histamine, and
prostaglandins along with Ils which are a group of cytokines including Il-4, Il-5, Il-8, and Il-
13. The trigeminal nerve mediates the perception of normal nasal airflow by action
potentials from the transient receptor potentials melastatin 8 (TRPM8) receptors which are
located in the mucosa. These TRPM8 receptors, the trigeminal “cool” thermoreceptors,
are triggered by the inspired air currents cooling the nasal mucosa providing the sense of
normal breathing.33,74,358e360 Obviously, there is a vibrant cellular defensive system living
and breathing in the neurovascular bundles located in nasal submucosa (lamina propria,
stroma) including the dendritic cells that present foreign proteins to T and B lymphocytes to
initiate immune responses. Supplementing the T and B lymphocytes, other specific
defensive cells include eosinophils, mast cells, basophils, and plasma cells.4,15e17

the nostril, then the mucous blanket can mechanically trap foreign elements such as
helminths, bacteria, viruses, fungi, pollens, and other particulate matter and with the
energetic mucociliary transport system deliver these substances to the posterior
pharynx to be swallowed demolished and destroyed. There is, moreover, the phys-
ical protection of the nasal pseudostratified ciliated columnar epithelial lining itself,
which functions as an effective barrier to external noxious elements. In addition, the
nasal mucosa and submucosa (lamina propria, the stroma) have both humoral and
cellular defensive capabilities including the antimicrobial proteins lactoferrin (Lf),
lysozyme (Ly), and human beta-defensin 1 (hBD-1).15e17 Added to these three ma-
jor nasal antimicrobial proteins, there are several other known antimicrobial proteins
and peptides, including statherin and secretory phospholipase A2, all have been
28 CHAPTER 1 Introduction and overview

identified and likely contribute to the total antimicrobial properties of human nasal
secretions.15 Recently, it was suggested that hBD-1 is an important component of the
innate immune response, particularly at mucosal surfaces, which are vulnerable to
colonization by potential pathogens. Defensins with their antimicrobial and immune
properties can both induce inflammation and suppress the inflammatory response
through discrete and specific mechanisms. Since these antimicrobial proteins Lf,
Ly, and hBD-1 are consistently contained in nasal secretions, the clinician must
realize that washing (lavage) these proteins away may interfere with the body’s ho-
meostatic mechanism and its ability to protect the nasal mucosa from dangerous bac-
teria including Klebsiella ozenae.
Nasal mucosal cells produce immunoglobulins IgA and IgG, leukotrienes, his-
tamine, prostaglandins along with interleukins (Ils), which are a group of cyto-
kines; some of the important ones include Il-4, Il-5, Il-8, and Il-13. Obviously,
there is a vibrant cellular defensive system living and breathing in the nasal sub-
mucosa including the dendritic cells which present foreign proteins to T and B lym-
phocytes to initiate immune responses. Supplementing the T and B lymphocytes,
other specific defensive cells include eosinophils, mast cells, basophils, and plasma
cells. Remember, the nasal mucosa correspondingly contains abundant seromuci-
nous and goblet cells; furthermore, this submucosa (lamina propria, stroma) fea-
tures an important network of sensory and autonomic neurovascular bundles
with an extraordinarily rich functioning vascular system with an existing dynamic
nasal cycle.
The autonomic nervous system-controlled nasal cycle allows for the spontaneous
congestion and decongestion of the nasal venous sinusoids, so the congested side is
the “resting” side of the nose while the decongested side is the “functioning” side.
Because of the nasal septum, the total nasal airway resistance remains relatively con-
stant and is calculated at a lower resistance level than either one of the individual
right- or left-sided nasal resistance values. How is it possible that the total nasal
airway resistance is lower than either one of the individual sides you ask? This is
because the calculation of total nasal airway resistance is based on the concept of
a parallel circuit and not a series circuit. Consider that nasal airway resistance is
not measured, you calculate nasal airway resistance by measuring transnasal pres-
sure and nasal air flow during the inspiratory and expiratory respiratory cycle. To
calculate nasal airway resistance, nasal airway pressure is divided by nasal air
flow. The parallel circuit formula for calculating total nasal airway resistance is
the product of the resistance of each right and left side divided by the sum of the right
and left side resistance, so the resultant total nasal airway resistance is less than
either one of the individual sides.
 3. Nasal physiology 29

What happens to the patient when the pseudostratified ciliated columnar respira-
tory epithelium of the nasal mucosa is wounded or the seromucinous and goblet cells
are resected? What happens to a patient when the submucosa is impaired, dimin-
ished, and damaged by the deft debrider tearing though those delicate neurovascular
bundles compressing the precious submucosal spaces with postsurgical choking scar
strewn with remnants of frayed and tattered autonomic and sensory neural tissue
filaments?
What happens to the patient when the respiratory and the defensive nasal phys-
iologic functions are partially, or in the extreme case totally destroyed; torn asunder
as it were, detached by disconnection from the corpus? Is this ablation passed off as a
minor misdemeanor or is it truly, as demanded by Huizing and de Groot, a capital
nasal crime?3,4
Who is damaged by this mucosal and submucosal punishment? Some surgeons
discount the consequences of harming normal nasal physiologic mechanisms or are
both unaware of ENS or rebuff the validity of the patient’s ENS symptoms and are
therefore reluctant to offer understanding and comfort to their patients by acknowl-
edging the existence of ENS or validating their patient’s complaints and their plain-
tive plea for help.2,18 In medicine, we cure rarely, we aid healing often, and we must
be compassionate, always.
With a varied and protean symptomatology, the clinical presentation of ENS may
challenge the most astute and experienced clinician, thereby defying diagnosis.
Consequently, a principal purpose of this text includes establishing the diagnostic
criteria for ENS, examining theories regarding etiology, evaluating effectiveness
of current consensus strategies for the management of inferior turbinate enlarge-
ment, while stressing prevention of ENS, thereby evading its devastating toll.
Ultimately, this contribution is worthwhile if awareness regarding ENS is raised
and scholarship is stimulated among all nasal and rhinoplasty surgeons regarding
fundamental nasal airway physiology and the recognition of the debilitating physical
and psychological suffering that ENS patients endure. The topics covered in this
book are outlined in Table 1.3.

Table 1.3 The empty nose syndrome (ENS) chapter outline.

CHAPTER 1 Introduction and overview
A. Introduction and overview
B. Empty nose syndrome (ENS) in print media, TV; with ubiquity on the World Wide
Web
C. Nasal physiology: Olfaction, breathing (“perfect nasal resistance”), internal nasal valve
area, defensive immunoglobulins, cytokines plus T and B lymphocytes
CHAPTER 2 The scope of the empty nose syndrome (ENS)
A. Definition: What is the empty nose syndrome (ENS)?
B. Symptoms of ENS
C. ENS or atrophic rhinitis? A definition of terms
1. Primary atrophic rhinitis
2. Secondary atrophic rhinitis
3. Differential diagnosis of atrophic rhinitis
Continued
30 CHAPTER 1 Introduction and overview

Table 1.3 The empty nose syndrome (ENS) chapter outline.dcont’d

D. Diagnosis of ENS
E. Iatrogenic wonderland-etiology
CHAPTER 3 Pathophysiology of the empty nose syndrome (ENS)
CHAPTER 4 Treatment options for the empty nose syndrome (ENS)
A. Medical
B. Surgical
C. Preventing ENS
CHAPTER 5 The turbinatesdan overview
A. Historical perspective
B. Turbinate anatomy
1. Anatomy of the middle turbinate
2. Anatomy of the inferior turbinate
C. Physical examination
D. Rhinologic evaluation with assessment tests and biopsy
CHAPTER 6 Brief history of evidence-based medicine (EBM)-David Sackett, MD
CHAPTER 7 The turbinatesdmanagement
A. Middle turbinate management
B. Inferior turbinate management
1. Classification: Inferior turbinate enlargement (“hypertrophy”)
2. Turbinate reduction: Surgical and nonsurgical procedures
a. Epithelial mucosal destruction: Trans mucosal approach (includingdpartial and
completedtotal turbinectomy)
1. Surgical resection-turbinectomy (partial or completedtotal)
2. Electrocautery
3. Laser therapy
4. Cryotherapy
b. Epithelial mucosal preservation: Sub mucosal approach
1. Submucosal soft tissue surgical reduction (conventional “cold knife”)
a. Submucosal soft tissue reduction only
b. Conchal bone reduction only
c. Combined: soft tissue and conchal bone reduction
2. Microdebrider
3. Radiofrequency
4. Coblation
5. Ultrasound
6. Electrocautery
c. Complimentary out-fracture (lateralization) techniques
1. Solitary-isolated and sole intervention
2. Combined with other procedures
d. Histopathology
CHAPTER 8 How to find the “best reduction method” for inferior turbinate enlargement
(“hypertrophy”)?
A. Context with discussion of some specific critical confounding questions
1. Randomized controlled trials (RCTs) searching for the “best reduction method”
from the literature
2. Future studiesddesigning the “best study” for finding the “best reduction method”
3. Thoughts for designing a “best study” for finding the “best reduction method” for
treating patients with inferior turbinate enlargement (“hypertrophy”)
4. When are randomized controlled trials (RCTs) NOT needed?
5. Asking answerable questions and empiricism versus rationalism
 3. Nasal physiology 31

Table 1.3 The empty nose syndrome (ENS) chapter outline.dcont’d

6. Are controlled trials (RCTs) really needed? Can they actually be accomplished in
surgery?
a. Absolute criteria for a valid RCT
b. Relative criteria for a valid RCT
7. Evidence first, but what to do when RCT data are limited, incomplete, inconclusive,
conflicting, or starkly nonexistent?
8. What are the influences of “placebo effects” in research and practice outcomes?
9. What are the ethics of using placebos in medicine?
10. What are the ethics of using placebos in surgery?
11. “Sham” surgery, is there an ethical place for research surgical trials or is it
forbidden?
12. What are the limitations, if any, to the doctrine of randomized controlled trials
(RCTs)?
13. Is there an ethical approach to surgical and invasive procedures within randomized
controlled trials (RCTs)?
14. What are the obligations and accountability to our patients regarding surgical
innovations?
15. What are the CONSORT requirements and what’s their importance for researchers
and journals?
16. What is propensity score matching (PSM) all about?
17. What about using clinical practice guidelines (CPGs) and associated conflicts of
interest (COI)?
18. What about practice replacement, reversal, and the nature of medical progress?
CHAPTER 9 Children and inferior turbinate reduction
CHAPTER 10 Medical journals: judging the quality of the editors, the peer reviewers, plus
the issue of plagiarism
CHAPTER 11 Review, finishing touches, and closure
A. Managing empty nose syndrome (ENS) Patients
1. Empty nose syndrome (ENS) exists
2. Pertinent nasal physiology
3. Symptoms of ENS
4. Etiology of ENS
5. Pathophysiology of ENS
6. Preventing ENS
7. Medical treatment of ENS
8. Surgical treatment of ENS
B. Evidence-based medicine (EBM)-David Sackett, MD
C. Consolidated standards of reporting trials (CONSORT)
D. Replacement or reversal of a medical practice
E. Managing middle turbinate enlargement
F. Managing inferior turbinate enlargement (“hypertrophy”) Evidence-based proposals
G. Regarding children
H. Summary, future directions, and closing thoughts
I. Appendix
This appendix contains seven items: (1) a brief history of Maurice H. Cottle, MD, (2) the
empty nose syndrome 6 questionnaire (ENS6Q), (3) the sino-nasal outcome test 20e25
(SNOT20-25) for ENS, (4) Nasal obstruction symptom evaluation (nose) instrument, (5)
the cotton test, and how to perform it, (6) the questionnaire generalized anxiety disorder
(GAD-7), (7) the patient health questionnaire-9 (PHQ-9) for depression.
 CHAPTER

The scope of the empty

nose syndrome (ENS)
2
1. Definition: what is empty nose syndrome (ENS)?
The term “empty nose syndrome” (ENS) was coined by the Mayo Clinic team (Sten-
kvist and Kern) in 1994 when Dr. Monika Stenkvist, visiting surgeon and scientist,
observed the noticeably and conspicuously empty nasal cavities on computerized to-
mography (CT) scans of patients missing almost all identifiable inferior and middle
turbinate mucosal structures secondary to surgical resection of the turbinates fol-
lowed by a multiple symptom complex arising months to years after their initial sur-
gery (performed at sites other than Mayo Clinic). Some examples of coronal CT
scans found in our practice exhibiting the common findings observed, not operated
at Mayo Clinic, and diagnosed with the ENS are located in Figs. 2.1e2.18.
By definition, ENS is primarily an iatrogenic condition, secondary to turbinate
trauma, in which a surgical resection removes various amounts of functioning nasal
turbinate mucosal and submucosal (lamina propria, stroma) tissue. ENS may occur
secondary to a non-surgical Turbinate Reduction Adjunctive Procedure (n-s TRAP),
which may also inflict significant turbinate trauma profoundly compromising nasal
function. In either case, the patient experiences the distinctive hallmark symptoms of
nasal obstruction “congestion,” (difficulty breathing, often a “paradoxical obstruc-
tion,” meaning obstructed breathing usually with “breathlessness” despite a widely
patent nasal airway, with a sense of suffocation) and nasal crusting along with
various protean symptoms arising months to years following the iatrogenic turbinate
trauma.
Specifically and by definition, the term surgery is the medical practice of man-
aging diseases, deformities, and injuries by actually “cutting” into a part of the
body while, on the other hand, the procedures of electrocautery, chemocautery, la-
sers, radiofrequency, coblation, or ultrasound are not surgery in the traditional “strict
sense” of “cold knife” cutting, but nonetheless they are currently covered beneath
the umbrella of “surgery,” although we prefer to label them n-s TRAPs.

Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00002-0 33

Copyright © 2024 Elsevier Inc. All rights reserved.
FIGURE 2.1
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is a cavernous expansion of the intranasal airway with the
absence of both middle and inferior turbinates that have been previously surgically
resected (removed-not by a Mayo Clinic surgeon) after bilateral total middle and inferior
turbinectomies. Note: We do not advocate total or subtotal turbinectomies for benign
turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.2
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is an absence of almost all of both inferior turbinates that
have been previously surgically resected (removed-not by a Mayo Clinic surgeon) after a
bilateral subtotal inferior turbinectomies. Note: We do not advocate total or subtotal
turbinectomies for benign turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
FIGURE 2.3
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is an absence of both inferior turbinates that have been
previously surgically resected (removed-not by a Mayo Clinic surgeon) after a bilateral
total inferior turbinectomies. Note: We do not advocate total or subtotal turbinectomies for
benign turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.4
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is an absence of almost all of both middle and inferior
turbinates that have been previously surgically resected (removed-not by a Mayo Clinic
surgeon) after a bilateral middle and subtotal inferior turbinectomies. Note: We do not
advocate total or subtotal turbinectomies for benign turbinate enlargement
(“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
FIGURE 2.5
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is an absence of the right middle turbinate and almost all
of both inferior turbinates that have been previously surgically resected 3(removed-not by
a Mayo Clinic surgeon) after a right middle turbinectomy and bilateral total inferior
turbinectomies. Note: We do not advocate total or subtotal turbinectomies for benign
turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.6
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is an absence of the right middle turbinate, an apparent
nasal septal deformity, and an absence of both inferior turbinates that have been
previously surgically resected (removed-not by a Mayo Clinic surgeon) after a bilateral
total inferior turbinectomies. Note: We do not advocate total or subtotal turbinectomies for
benign turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
FIGURE 2.7
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is an absence of the right middle turbinate and almost all
of both inferior turbinates, more on the right than the left, that have been previously
surgically resected (removed-not by a Mayo Clinic surgeon) after bilateral subtotal inferior
turbinectomies. Note: We do not advocate total or subtotal turbinectomies for benign
turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.8
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is a nasal septal deformity and what appears to be chronic
mucosal changes in the left ethmoid sinus and left maxillary sinus. There is an absence of
both middle and inferior turbinates that have been previously surgically resected
(removed-not by a Mayo Clinic surgeon) after bilateral total middle and inferior
turbinectomies. Note: We do not advocate total or subtotal turbinectomies for benign
turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
FIGURE 2.9
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There appears to an atrophic change of the right middle
turbinate and a reduction (subtotal resection) of the right inferior turbinate. There is an
absence of the left middle turbinate and a subtotal reduction left inferior turbinate; they
have been previously surgically resected (removed-not by a Mayo Clinic surgeon) after a
left middle turbinectomy and bilateral subtotal inferior turbinectomies. Note: We do not
advocate total or subtotal turbinectomies for benign turbinate enlargement
(“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.10
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” Both middle turbinates are absent and a near total reduction
(subtotal resection) of both inferior turbinates. They have been previously surgically
resected (removed-not by a Mayo Clinic surgeon) after bilateral middle turbinectomies
and bilateral subtotal inferior turbinectomies. Note: We do not advocate total or subtotal
turbinectomies for benign turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
 2. Symptoms of the empty nose syndrome (ENS) 39

FIGURE 2.11
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” The left maxillary sinus “appears” to be filled with bone or
another dense material. There is an absence of the left middle and inferior turbinate along
with a reduction of the right middle and inferior turbinates. They have been previously
surgically resected (removed-not by a Mayo Clinic surgeon) after left middle and inferior
turbinectomies and right subtotal middle and inferior turbinectomies. Note: We do not
advocate total or subtotal turbinectomies for benign turbinate enlargement
(“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

2. Symptoms of the empty nose syndrome (ENS)

One of the characteristic symptoms of ENS includes a “paradoxical sense of nasal
airway obstruction.”18e20 The paradox lies in the patient’s perceived sense of prob-
lematic nasal breathing despite a widely patent nasal cavity following varying
amounts of mucosal and submucosal turbinate tissue resection or submucosal injury
subsequent to an n-s TRAP. The diagnosis of ENS is challenging because the patient
may experience a long lag time (unpredictably varying from months to years) before
symptoms appear, which are almost always nasal airway obstruction (“congestion”)
and associated nasal crusting and postnasal discharge, while many symptoms are
assorted, protean, and inconsistent, but what is consistent and unifying is the fact,
by definition, that almost every patient with ENS has had a previous documented
nasal turbinate operative resection or n-s TRAP. These ENS patients experience
many specific symptoms listed in Table 2.1. Some findings seen in ENS patients
40 CHAPTER 2 The scope of the empty nose syndrome (ENS)

FIGURE 2.12
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” There is a reduced left middle turbinate and an absence of the
left inferior turbinate along with an absence of the right inferior turbinate. They have been
previously surgically resected (removed-not by a Mayo Clinic surgeon) after bilateral
inferior turbinectomies and a left subtotal middle turbinectomy. There are inflammatory
changes in the ethmoid sinuses, greater on the left than the right with inflammatory
changes in the left maxillary sinus. There appears that the “bilateral antrostomies” have
closed with soft tissue, scar. Note: We do not advocate total or subtotal turbinectomies for
benign turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

on intranasal exam range from atrophy, crusting, to absent turbinate tissue as viewed
in Figs. 2.19e2.24.

3. Empty nose syndrome or atrophic rhinitis? A definition of

terms
1. Primary atrophic rhinitis
2. Secondary atrophic rhinitis
3. Differential diagnosis of nasal atrophy
Conceptually, there is some controversy as to whether ENS should be considered
an iatrogenic entity with a secondary atrophic rhinitis or whether atrophic rhinitis
should be considered its own distinct clinical entity unrelated to surgical interven-
tion. Chhabra and Houser contend that ENS must be viewed separately from
FIGURE 2.13
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” The middle turbinates are smaller on the right than the left, and
both inferior turbinates have been subtotally reduced. They have been previously
surgically resected (removed-not by a Mayo Clinic surgeon) after bilateral subtotal middle
turbinectomies and bilateral subtotal inferior turbinectomies. Note: We do not advocate
total or subtotal turbinectomies for benign turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.14
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome.” Both middle turbinates are absent, and both inferior turbinates
are almost totally nonexistent. They have been previously surgically resected (removed-
not by a Mayo Clinic surgeon) after bilateral total middle turbinectomies and bilateral
subtotal inferior turbinectomies. Note: We do not advocate total or subtotal turbinectomies
for benign turbinate enlargement (“hyperplastic”).
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
FIGURE 2.15
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome” after a previous rhinoplasty with the absence of both inferior
turbinates and the right middle turbinate and a possible subtotal reduction of the left
middle turbinate. This rhinoplasty operation was performed at another institution and not
at Mayo Clinic. For the record, we adamantly and categorically denounce inferior
turbinectomy as part of a routine rhinoplasty operation.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.16
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome” after a previous rhinoplasty with almost a total absence of both
inferior turbinates. This rhinoplasty operation was performed at another institution and not
at Mayo Clinic. These inferior turbinates have been surgically resected (removed-not by a
Mayo Clinic surgeon) after bilateral subtotal inferior turbinectomies. For the record, we
adamantly and categorically denounce inferior turbinectomy as part of a routine
rhinoplasty operation.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
 3. Empty nose syndrome or atrophic rhinitis? A definition of terms 43

FIGURE 2.17
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome” after a previous rhinoplasty performed elsewhere. The CT scan
on the left is preoperative. The CT scan on the right is after a rhinoplasty operation
performed at another institution and not at Mayo Clinic. There is an absence of the right
middle turbinate and almost total absence of both inferior turbinates. The right middle
turbinate and both inferior turbinates have been surgically resected (removed-not by a
Mayo Clinic surgeon) after right middle turbinectomy and bilateral total inferior
turbinectomies. For the record, we adamantly and categorically denounce inferior
turbinectomy as part of a routine rhinoplasty operation.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

atrophic rhinitis despite “similarities in the symptoms,” especially the symptoms of

“paradoxical nasal airway obstruction, congestion, dryness, and crusting.”21 They
argue that ENS, unlike atrophic rhinitis, is not always associated with obvious
visible nasal mucosal atrophy, and that ENS is exclusively iatrogenic in origin
and does not have a clear link to pathologic organisms.18,20 Other authors agree
that the atrophy and dryness of the nasal mucosa seen in ENS can occur either sub-
sequent to a surgical turbinate reduction or following a n-s TRAP.18,21,22
We agree, in part, with Chhabra and Houser21 that ENS is almost always and
exclusively iatrogenic in origin and that ENS is not always associated with obvious
nasal atrophy. We consider ENS as a subcategory of atrophic rhinitis, a secondary
atrophic rhinitis. Primary atrophic rhinitis is almost exclusively associated with
the bacterial infections of Klebsiella pneumoniae ozaenae. For clarity, recognize
44 CHAPTER 2 The scope of the empty nose syndrome (ENS)

FIGURE 2.18
Coronal CT scan of a patient exhibiting the common findings seen in patients with the
“empty nose syndrome” after a previous rhinoplasty performed elsewhere. The CT scan
on the left is preoperative. The CT scan on the right is after a rhinoplasty operation
performed at another institution and not at Mayo Clinic. Both middle turbinates are
absent. The right inferior turbinate is absent, and the left inferior turbinate is almost totally
absent. These turbinates have been surgically resected (removed-not by a Mayo Clinic
surgeon) after bilateral middle and inferior total turbinectomies. For the record, we
adamantly and categorically denounce inferior turbinectomy as part of a routine
rhinoplasty operation.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

that ozena is a type of primary atrophic rhinitis caused by the bacterial infection of
Klebsiella pneumoniae ozaenae.
Another Klebsiella infection is called rhinoscleroma, which can present simi-
larly to ozena in its earliest stage. Rhinoscleroma is caused by Klebsiella pneumo-
niae rhinoscleromatis, and it is important to realize that this infection is chronic
and the gram-negative rods, particularly Klebsiella, are increasingly resistant to
antibiotics.23
For comprehensive clarity, we classify ENS as a secondary atrophic rhinitis. Pre-
vious terminologies found in the literature for atrophic rhinitis unfortunately added
 3. Empty nose syndrome or atrophic rhinitis? A definition of terms 45

Table 2.1 The various and fluctuating symptoms seen in the empty nose
syndrome (ENS).
1. Paradoxical nasal airway obstruction (nasal “congestion,” difficult nasal breathing
usually with “breathlessness,” often with a sense of suffocation)
2. Nasal crusting, nasal dryness (“rhinitis sicca”), bleeding (varying degrees of epistaxis)
3. Inability to feel nasal airflow
4. Foul (fetid) odor (often noted by others) with thick nasal discharge and postnasal “drip”
5. Anosmia or hyposmia
6. Headache
7. Localized nasal facial pain (posttraumatic neuropathic pain)
8. Disturbed sleep (with secondary symptoms of fatigue and lethargy)
9. Aprosexia nasalis (inability to concentrate)
10. Psychological alterations (anxiety, clinical depression, suicidal ideation)
11. Disturbance in the sense of “well-being”
12. Impaired quality-of-life

FIGURE 2.19
Endoscopic intranasal view of a patient exhibiting the common finding of extensive
intranasal atrophy (secondary atrophic rhinitis) often seen in patients with the “empty
nose syndrome.” Note the previously performed subtotal resection of the left inferior
turbinate as well as the left inferior meatal antrostomy with mucopurulent material
exuding from the maxillary sinus onto the nasal floor. The perforation of the nasal septum
is also visible. The previous surgical operation was performed at another institution and
not at Mayo Clinic.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
46 CHAPTER 2 The scope of the empty nose syndrome (ENS)

FIGURE 2.20
Endoscopic intranasal view of a patient exhibiting the common finding of extensive
intranasal crusting and atrophy (secondary atrophic rhinitis) often seen in patients with
the “empty nose syndrome.” Note the absence of the inferior turbinate on the left and the
large perforation of the nasal septum. The previous surgical operation was performed at
another institution and not at Mayo Clinic.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.21
Endoscopic intranasal view (“empty” right nasal chamber) in a patient exhibiting the
common gross findings resulting from a previous total inferior turbinectomy and
commonly seen in patients with the “empty nose syndrome.” The previous total inferior
turbinectomy was performed at another institution and not at Mayo Clinic.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
 3. Empty nose syndrome or atrophic rhinitis? A definition of terms 47

FIGURE 2.22
Intraoral view of a patient exhibiting the common finding of mucopurulent postnasal
discharge commonly seen in patients with the “empty nose syndrome.”
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

to the perplexing puzzle by using the terms atrophic rhinitis, rhinitis sicca, ozaena,
ozena, nasal atrophy, primary and secondary rhinitis atrophicans, rhinitis atrophi-
cans, and dry nose among others, interchangeably at times, utterly without precise
definition, differentiation or distinction among the various subclassifications of atro-
phic rhinitis. The principal purpose of discussing atrophic rhinitis, at this juncture, is
to clearly eliminate any misunderstandings by offering a precise terminology. With
this definition of terms, atrophic rhinitis is specifically classified into (1). primary
atrophic rhinitis and (2). secondary atrophic rhinitis.

3.1 Primary atrophic rhinitis

Primary atrophic rhinitis is often called ozena, which is merely the descriptive
Greek term meaning “stench” (strong unpleasant odor). Primary atrophic rhinitis
has decreased in incidence in the Western world during the past 100 years, which
is likely due to advanced hygiene and the liberal use of antimicrobials for chronic
nasal infections. While the exact etiology of primary atrophic rhinitis is still un-
known, what is known is that almost all of these primary atrophic rhinitis patients
have culture-positive bacterial infections with Klebsiella pneumoniae ozaenae.18,23
There is progressive atrophy of the nasal mucosal elements including the epithelium,
the submucosal glandular and vascular structures along with osteoclast infiltration of
the bony concha of the turbinates. The pseudostratified ciliated respiratory epithe-
lium of the nasal mucosa is replaced by squamous metaplasia along with atrophy
of the seromucinous and goblet cells along with scarring of the submucosal (lamina
propria, stroma). The submucosal vasculature is not only diminished in quantity but
also there is definitive evidence of endarteritis.18 The fact that mucociliary transport
has been compromised, along with a reduced number of glandular elements, the
FIGURE 2.23
Endoscopic intranasal view of a patient exhibiting the common finding of intranasal atrophy,
with some suggested evidence of mucopurulent material posteriorly after a previously
performed right partial (subtotal) inferior turbinectomy often seen in patients with the
“empty nose syndrome.” The previous right partial (subtotal) inferior turbinectomy was
performed at another institution and not at Mayo Clinic. If a biopsy was performed at the
head of the right inferior turbinate remnant, then squamous metaplasia would be found
replacing the normal pseudostratified ciliated columnar respiratory epithelium.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).

FIGURE 2.24
Endoscopic intranasal view of a patient exhibiting the common finding of intranasal
atrophy after a previously performed right total inferior turbinectomy often seen in patients
with the “empty nose syndrome.” The previous right total inferior turbinectomy was
performed at another institution and not at Mayo Clinic.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights
Reserved).
 3. Empty nose syndrome or atrophic rhinitis? A definition of terms 49

secretions are thickened, forming crusts, encouraging bacterial multiplication, while

the products of bacterial metabolism release a noxious gas perceived as a vile fetid
odor. On the other hand, patients with a secondary atrophic rhinitis rarely demon-
strate positive cultures for Klebsiella pneumoniae ozaenae. Most assuredly, primary
atrophic rhinitis is a debilitating nasal mucosal and submucosal progressive disorder
with a constellation of conspicuously prominent “hallmark” symptoms, which are
especially and particularly analogous to ENS including:
a. Nasal airway obstruction
b. Nasal dryness, nasal crusting, and bleeding (varying degrees of epistaxis)
c. Foul (fetid) odor (often noted by others) with thick nasal discharge
d. Anosmia
e. Headache
f. Localized facial pain
g. Psychological alterations including depression
What is almost universal and remarkable in patients with primary atrophic
rhinitis is the wide-open intranasal airway; yet, the patient often paradoxically com-
plains of nasal airway obstruction (difficulty breathing despite the broadly patent
nasal airway). In essence, primary atrophic rhinitis is of unspecified etiology,
with a spontaneous onset, and a slowly progressive relentless course consistently
associated with the bacteria Klebsiella pneumoniae ozaenae.

3.2 Secondary atrophic rhinitis

Secondary atrophic rhinitis, as the term implies and by definition, develops subse-
quent to either a surgical or nonsurgical nasal trauma or may occur as a nasal mani-
festation of a systemic illness or rationally subsequent, secondary, to the inexorable
aging process. Secondary atrophic rhinitis patients consistently have predisposing
factors for developing their symptom complex including surgery for turbinate vol-
ume reduction to alleviate nasal breathing obstruction, which may induce the
ENS producing a secondary atrophic rhinitis. This secondary atrophic rhinitis
does not occur instantaneously but only materializes months to years following
the initial surgical intrusion and trauma. There is a vast list of both surgical and
nonsurgical adjunctive procedures designed to improve nasal breathing by treating
enlargement (“hypertrophy”) of the inferior turbinate, which may in turn spawn a
secondary atrophic rhinitis. Based on our observations and experience with hun-
dreds of ENS patients, any of the surgical procedures listed in Table 2.2 can produce
ENS.18 Principally, the surgical turbinate reduction procedures of the turbinates have
regularly been undertaken without any preoperative functional physiological testing.
The adjunctive procedures which we term: n-s TRAPs are listed in Table 2.3.25,26
Table 2.4 Summarizes various treatment modalities created and crafted for infe-
rior turbinate enlargement (“hypertrophy”) collected and presented by Hol and Hui-
zing in 2000 dating back to the middle of the 19th century.25 With the passage of
50 CHAPTER 2 The scope of the empty nose syndrome (ENS)

Table 2.2 Surgical turbinate reduction procedures (inferior and or middle)

able to produce the empty nose syndrome (ENS).
1. Total turbinectomy
2. Partial turbinectomy (inferior and or middle)
3. Crushing and mucosal trimming procedures
4. Posterior inferior turbinate tip resection
5. Submucosal tissue resection-inferior turbinate (broadly called turbinoplasty)
6. Submucosal resection of the conchal bone (broadly called turbinoplasty)
7. Combined resection of submucosal tissue and conchal bone (broadly called
turbinoplasty)

Table 2.3 Non-surgical Turbinate Reduction Adjunctive Procedures

(n-s TRAPs).a
1. Thermal coagulation (electrocautery)
2. Chemocoagulation
3. Injection of corticosteroids, sclerosing agents
4. Cryosurgery
5. Laser surgery
6. Radiofrequency ablation
7. Coblation (derived from “controlled ablation” meaning tissue removal in a controlled
manner or “cold ablation” meaning tissue removal by a reduced or “colder” temperature)
8. Ultrasound
a
Specifically, and by definition, the term surgery is the medical practice of managing diseases,
deformities, and injuries by actually “cutting” into a part of the body, while, on the other hand, the
procedures of electrocautery, chemocautery, lasers, radiofrequency, coblation, or ultrasound are not
surgery in the traditional “strict sense” of “cold knife” cutting, but nonetheless they are currently covered
beneath the umbrella of “surgery,” although we prefer to label them: “non-surgical” Turbinate
Reduction Adjunctive Procedure (n-s TRAP).

time, we added radiofrequency (2004) and ultrasound (2010) to the list of treatment
options for inferior turbinate enlargement (“hypertrophy”).

3.3 Differential diagnosis of nasal atrophy

There are a number of systemic illnesses that the physician needs to be interested
in, such as lymphoma, with epistaxis, also termed midline destructive lesions with
various additional names such as idiopathic midline granuloma or lethal midline
granuloma or polymorphic reticulosis because these systemic diseases may have
an initial rhinologic presentation, which is designated a nasal manifestation of a
systemic disease. For example, a granulomatous disorder such as sarcoidosis, or
 3. Empty nose syndrome or atrophic rhinitis? A definition of terms 51

Table 2.4 History of treatments for Inferior Turbinate Enlargement

(hypertrophy).4,25
1. Thermal coagulation, electrocautery 1845e1880
2. Chemocoagulation, chemotherapy 1869e1890
3. Turbinectomy 1882
4. Lateralization, lateropexia (out-fracture) 1904
5. Submucous resection of the turbinate bone 1906e1911
6. Crushing + trimming, partial resection 1930e1953
7. Injection of corticosteroids 1952
8. Injection of sclerosing agents 1953
9. Vidian neurectomy 1961
10. Cryosurgery 1970
11. Laser surgery 1977
12. Turbinoplasty 1982
13. Powered instruments (shaver, microdebrider) 1994
14. High radiofrequency radiation 1998
With the passage of time, we added to their list:
15. Radiofrequency 2004 (Nease and Krempl)26
16. Ultrasound 2010 (Gindros et al.)27

mycobacterial tuberculosis, leprosy or syphilis*, or other rarer infectious diseases

may present with nasal obstruction, crusting, epistaxis, anosmia, and face pain.
*Syphilis is the well-known infectious disease produced by the spirochete Treponema pal-
lidum. Because of its diverse, and at times confusing, clinical and histopathologic portrait,
syphilis may appear in any of three specific phases: primary syphilis presents as an ulcer-
ation (chancre), secondary syphilis has a variable histology and may be easily misinter-
preted, while tertiary syphilis presents as a necrotizing granulomatous inflammation.

Autoimmune diseases such as granulomatosis with polyangiitis (formerly known

as Wegener’s granulomatosis) may present with nasal obstruction, nasal crusting,
foul (fetid) odor, and epistaxis. Other autoimmune diseases including relapsing pol-
ychondritis have the nasal manifestations of nasal atrophy with crusting and
epistaxis and may coexist with an underlying malignant disease. Another autoim-
mune disease, eosinophilic granulomatosis with polyangiitis (necrotizing vasculitis)
formerly Churg-Strauss syndrome can present with nasal obstruction (difficulty
breathing), nasal crusting, and epistaxis. Sjogren’s syndrome is a progressive auto-
immune inflammation with nasal manifestations of nasal airway obstruction, dry-
ness, crusting, epistaxis, and hyposmia. In considering the differential diagnosis
of ENS, physicians and surgeons must also consider the possibility of an underling
systemic disorder or medication-induced nasal dryness and associated difficulty
52 CHAPTER 2 The scope of the empty nose syndrome (ENS)

Table 2.5 Differential diagnosis of nasal atrophy.

A. Primary atrophic rhinitis
B. Secondary atrophic rhinitis
1. Empty nose syndrome (ENS)
2. Lymphoma also called:
a. Idiopathic midline granuloma
b. Lethal midline granuloma
c. Polymorphic reticulosis
3. Granulomatous
a. Leprosy
b. Rhinoscleroma, gram-negative bacilli, Klebsiella pneumoniae rhinoscleromatis
c. Sarcoidosis
d. Tertiary syphilis (necrotizing granulomatous inflammation) a
e. Tuberculosis
4. Autoimmune
a. Granulomatosis with polyangiitis (formerly Wegener’s granulomatosis)
b. Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome)
c. Relapsing polychondritis
d. Sjogren’s syndrome
5. Rhinitis of “aging” (also known as “geriatric” rhinitis, “senile” rhinitis)
6. Surgical and nonsurgical turbinate trauma
7. Other
a
Syphilis is the well-known infectious disease produced by the spirochete Treponema pallidum.
Because of its diverse, and at times confusing, clinical and histopathologic portrait, syphilis may appear
in any of three specific phases: primary syphilis presents as an ulceration (chancre), secondary syphilis
has a variable histology and may be easily misinterpreted, while tertiary syphilis presents as anecrotizing
granulomatous inflation.

Table 2.6 Diagnostic workup for intranasal atrophic changes.

1. “Routine” blood studies
2. Sedimentation rate
3. C-reactive protein
4. Antineutrophil cytoplasm antibodies (c-ANCA)
5. Additional serologic assays as indicated
6. General bacterial culture and sensitivity
7. Analysis for acid-fast bacillus
8. Culture for fungi and anaerobes
9. Intranasal tissue biopsy

with nasal breathing. Table 2.5 is a list of the probable (most likely) differential diag-
nosis of a patient with nasal atrophy.
All of these disorders must be considered in the differential diagnosis of nasal
atrophic changes (nasal atrophy) observed on the physical examination and corre-
lated with the patient’s symptomatology, which may require some of the following
studies depending on your clinical suspicion, remembering that intranasal tissue bi-
opsy is usually, but not always, diagnostically decisive.
A summary of the diagnostic workup for intranasal atrophy is seen in Table 2.6.
 3. Empty nose syndrome or atrophic rhinitis? A definition of terms 53

Consultation with colleagues in internal medicine, infectious disease, and rheu-

matology may be helpful. While secondary atrophic rhinitis, in this classification, is
more commonly encountered in the Western world than primary atrophic rhinitis,
both disorders share overlapping symptoms with entirely different etiologies.
In summary, the physician and surgeon can distinguish between primary and sec-
ondary atrophic rhinitis as follows: primary atrophic rhinitis is defined when the
“hallmark” symptoms occur without a definite antecedent cause or trigger in the
absence of surgical or nonsurgical nasal trauma, (n-s TRAPs) without any evidence
of granulomatous or inflammatory autoimmune diseases, with a positive culture for
Klebsiella pneumoniae ozaenae.
Secondary atrophic rhinitis frequently has a definitive and indisputable ante-
cedent cause such as surgery, systemic illness, or the aging process together with
bacterial culture findings almost always negative for Klebsiella pneumoniae ozae-
nae. Overall, primary atrophic rhinitis is a debilitating chronic disorder heralded
by a constellation of symptoms with an abnormally patent nasal airway with the pa-
tient complaining of nasal airway obstruction. Diagnosis is aided by history, phys-
ical examination, classic symptomatology confirmed with imaging studies, tissue
biopsy with histology, and culture positive for Klebsiella pneumoniae ozaenae,
while considering an extensive differential diagnosis and ruling out systemic illness.
It must also be acknowledged that changes in the nasal mucosa may be part of the
inexorable aging process.
With an ever-increasing elderly population, newly descriptive terms have been
introduced into the literature such as “geriatric” rhinitis, “senile” rhinitis, or the
rhinitis of “aging,” all of which are describing the atrophic nasal mucosal changes
secondary to a loss of submucosal seromucinous and goblet cells, decrease of
collagen, and an alteration in mucosal microvascular blood flow. Certainly, the
rhinitis of “aging” is an example of secondary atrophic rhinitis. Senior citizens often
have thin atrophic nasal mucosa and symptoms of nasal crusting, thickened nasal
secretions, nasal obstruction, and a decreased olfactory acuity. Complicating issues
include the fact that many older patients are medicated with diuretics, beta blockers,
and psychological medications that have known side effects including nasal dryness
and difficulty breathing secondary to nasal airway obstruction. A list of various med-
ications with the side effect of dry nose is seen in Table 2.7.
Based on a literature review, and our own combined clinical experience, the ev-
idence is undeniable that ENS is an iatrogenic disorder with secondary atrophic

Table 2.7 Various medications with the side effect of dry nose.
1. Doxepin (tricyclic antidepressants)
2. Methyldopa (antiadrenergic) for hypertension
3. Sympathomimetics (local-topical)
4. Antihistamines (first generation)
5. Retinoids (1%e10%)
54 CHAPTER 2 The scope of the empty nose syndrome (ENS)

rhinitis. This secondary atrophic rhinitis develops subsequent to the surgical resec-
tion of functioning turbinate tissue or nonsurgical-induced mucosal damage result-
ing from an adjunctive procedure to the turbinates (n-s TRAP) There are many
physiological reasons to explain why some patients undergoing a turbinate proced-
ure experience mucosal damage secondary to either an “excessive invasive” surgical
resection or a “minimally invasive” n-s TRAP. These patients can subsequently
develop symptoms of ENS, as nasal mucosal atrophy ensues into the future and
perhaps exacerbating the aging process. Aside from a paradoxical sense of nasal
airway obstruction, dryness, and crusting, psychiatric manifestations (clinical
depression and or anxiety with suicidal ideation) are found in both the ENS and
other patients with a secondary atrophic rhinitis. In a Mayo Clinic study, among
the 242 atrophic rhinitis patients (primary atrophic rhinitis n ¼ 45, without a history
of nasal surgery, secondary atrophic rhinitis, with a history of nasal turbinate sur-
gery n ¼ 197), more than half (52%) experienced an associated reactive depression,
evidenced by positive findings of the Minnesota Multiphasic Personality Inventory
(MMPI) instrument.18
Given the difficulty characterizing ENS, the incidence or probability of devel-
oping ENS after a turbinate procedure is unknown, unpredictable, and usually un-
able to be conveyed to the patient preoperatively. Another drawback to tracking
the disease is that ENS manifestations, signs and symptoms, may occur shortly after
the turbinate procedure, or may require months or even years to evolve progressing
to become symptomatic and consistent with a secondary atrophic rhinitis pic-
ture.18,21 In 1985, almost 10 years prior to defining ENS, Moore et al.,2 from the Uni-
versity of Nebraska, found an overwhelming majority of patients at three to five
years subsequent to a bilateral total inferior turbinectomy experiencing symptoms
that now would be consistent with ENS. In the same cohort of patients seen at
two years following initial surgery, very few patients had any symptoms suggestive
of ENS.2 As previously stated, these findings led their team to denounce total infe-
rior turbinectomy, warning the profession that symptoms may not become obvious
pending the passage of years following the initiating surgery. We should recognize
and acknowledge patient complaints regarding nasal symptoms even if they occur
many years after nasal procedural interventions. It may take an unspecified aggre-
gate of time, for any given individual, at times measured in years, before the breath-
ing and defensive nasal functions devolve into symptomatic blatant ENS. Again,
realize that there are numerous medications that may generate a side effect of dry
nose are seen in Table 2.7.

4. Diagnosis of ENS
The variety and intensity of symptoms seen in ENS cannot be predicted based upon
the gross amount of nasal turbinate tissue surgically resected, removed, or damaged
following any one of a number of turbinate reduction procedures. The bedrock of
medical diagnosis is the history and physical examination findings, and remains
 4. Diagnosis of ENS 55

unwavering in our practice, the massive majority of patients with ENS presented
with a history and findings of previous trauma (surgical and nonsurgical) to the nasal
turbinates. These findings included surgically absent, reduced, or damaged turbinate
mucosal tissue which secondarily initiated a disruption of the normal functioning
nasal mucosa. When thinking about the nasal mucosa, recall that the nasal mucosa
encompasses the entire pseudostratified ciliated respiratory nasal epithelium
including the subepithelial submucosa (lamina propria, stroma) neurovascular and
active glandular secreting structures. The neurological connections include both a
sensory and the autonomic nervous systems. If we consider the nasal mucosa as
the “organ of the nose,” any operative procedure or disease process that disturbs
the functioning nasal mucosa may theoretically provoke and trigger ENS, as an
example of secondary atrophic rhinitis. This includes surgeries that “significantly”
damage the nasal mucosa (including partial or complete turbinate resection), in addi-
tion to relatively “minor” procedures producing ENS symptoms, which have been
reported following laser turbinate reduction.18 “Damaged mucosa” does not simply
and exclusively include nasal turbinate mucosal resection. We, as well as
others,18e27 have repeatedly observed patients with severe ENS symptoms in the
absence of any removal of nasal mucosa but who suffered symptomatic damage
from “simple” or “minor” turbinate procedures including the listed n-s TRAPs
seen in Table 2.3.25,26 The sine qua non for diagnosing ENS is evidence of the classic
symptoms subsequent to a documented history of a preceding nasal surgical or
nonsurgical intervention with removal or traumatic impairment of the nasal turbi-
nates seen in Table 2.1. Complicating the diagnosis of ENS is the fact that these
ENS symptoms may not appear until a lengthy number of months or even years
ensue after the initial nasal traumatic intervention and these symptoms may be expe-
rienced by patients with other disorders.18,28e30 Accordingly, a differential diag-
nostic challenge is presented to the clinician attempting to accurately diagnose
ENS patients and summarized in Table 2.5.
In the past few years, several validated tests have been introduced to aid in diag-
nosing ENS. The first is the Empty Nose Syndrome 6 Questionnaire (ENS6Q) ques-
tionnaire, which is a validated survey specifically designed to support the diagnosis
of ENS.31 This ENS6Q contains many common, but far from comprehensive, ENS
symptoms including:
1. Nasal suffocation
2. Nasal burning
3. Nasal openness
4. Nasal crusting
5. Nasal dryness
6. Impaired air sensation through the nasal cavities
The second validated test is termed the “cotton test.” In this test, a piece of dry
cotton is introduced into the nose adjacent to the head of the inferior turbinate and
remains in place for approximately 30 min. The patient performs the ENS6Q test
before, during, and after the “cotton test,” and if they experience improvement,
56 CHAPTER 2 The scope of the empty nose syndrome (ENS)

evaluated on a 5-item transition score, then a diagnosis of ENS is strengthened and

theoretically, at least, a “beneficial” surgical intervention might be considered.32
Recently, in 2020, Gill and associates33 noted an increased interest in ENS as a
legitimate “physiologic disease entity” obliging clinicians to become familiar with
current diagnostic tools, thereby allowing ENS validation. The reality of being able
to diagnose ENS ultimately leads physicians toward intelligent management of dis-
tressed ENS patients, many of whom (up to 66%) suffer significant psychological
anguish requiring compassionate, time-consuming counsel. Many of the Mayo pa-
tients (125/242,52%) were also diagnosed with psychological pain especially depres-
sion as evidenced by the MMPI and/or in consultation with a Mayo Clinic
psychiatrist.18
The ENS6Q may supplement the history coupled with the intranasal examination
that supports attaining a reasoned diagnosis of ENS. The in-office “cotton test” may
be helpful to identify patients who might conceivably experience symptomatic
improvement from a turbinate “replacement” graft or implant. Recognize that the
CT scan, computational fluid dynamics, and intranasal trigeminal nerve function
testing presently are insufficient to corroborate and confirm the diagnosis of ENS.31

5. Iatrogenic wonderland-etiology of ENS

For our group,18 and others2e4,18e28, the etiology of ENS remains clearly and un-
doubtedly a secondary atrophic rhinitis, that is secondary to a preceding nasal sur-
gical turbinate reduction procedure on the inferior and or the middle turbinate
Table 2.2. ENS may also occur with nasal mucosal trauma secondary to one or
more n-s TRAPs. Table 2.3. All of the symptoms in patients with the ENS are sub-
sequent to disturbances of one or more of the three primary physiologic nasal func-
tions of olfaction, breathing (respiration), and defense summarize in Table 2.2.
As previously cited, there are a number of systemic illnesses that the physician
needs to be cognizant of because the symptomatic complaints of difficulty breathing,
crusting, epistaxis with the findings of atrophic mucosal changes may appear as a
secondary atrophic rhinitis which necessitates thinking of the differential diagnosis
of nasal atrophy as outlined and summarized in Table 2.5. Several of these systemic
illnesses presenting with nasal manifestations are critical to accurately diagnose
since some of these disorders may be deadly.
 CHAPTER

Pathophysiology of the
empty nose syndrome
(ENS) 3
Although scientific research regarding nasal physiology, the essence of nasal func-
tion, has increased considerably, there are, according to the literature, still insuffi-
cient preoperative objective studies to guide surgical practice. Germane to the
state of development of scientific advancement in measuring nasal physiological
function, it is noted that the eminent scientist Lord Kelvin (Sir William Thompson
1824e1907) remarked:
“I often say that when you can measure what you are speaking about, and express
it in numbers, you know something about it; but when you cannot measure it,
when you cannot express it in numbers, your knowledge is a meagre and unsat-
isfactory kind; it may be the beginning of knowledge, but you have scarcely in
your thoughts advanced to the state of Science, whatever the matter may be.” *
*Popular Lectures and Addresses (PLA), 1891e1894, Volume 1 of three volumes, “Electrical Units
of Measurement,” 1883-05-03 by Lord Kelvin.
Often the nasal surgeon determines the functional capacity of the nasal “organ”
by observation and subjective patient reporting alone, as evidenced by the abundant
absence of objective testing data in the majority of papers in the literature dealing
with almost any aspect of nasal surgery. The justification of this “observational”
practice stems from a number of factors. Although some objective nasal functional
tests are available, few are routinely used by practicing surgeons. In addition, there is
an associated absence of medical or patient community pressure demanding func-
tional testing prior to any nasal surgery including rhinoplasty. Who among us, but
the most imprudent and cavalier would perform otologic surgery without a preoper-
ative audiogram? In reality, patients present for rhinoplasty or for complaints of
nasal airway subjective obstructive symptoms (difficulty breathing) and surgeons
willingly operate based on the patient’s subjective symptoms coupled with their
“observational” assessment alone. The “success” of the surgery simply relies
upon the patient’s subjective sense of change in their nasal airway function, and
the surgeon’s physical examination or photographic comparison. There has been
objective, evidence-based data to support a correlation between the patient’s subjec-
tive sense of nasal breathing improvements following internal nasal valve surgery
and the surgeon’s observational findings on clinical examination.36,37 Surgeons
cite these papers as credible scientific evidence supporting a long-held belief that
the combination of the patient’s subjective sense of nasal breathing and the surgeon’s

Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00003-2 57

Copyright © 2024 Elsevier Inc. All rights reserved.
58 CHAPTER 3 Pathophysiology of the empty nose syndrome (ENS)

findings on careful history and physical examination is sufficient to achieve high-

quality outcomes from functional nasal breathing surgery.
When it comes to turbinate surgery, however, there is presently no agreed upon
“right amount” of functional tissue to be removed or preserved. Patients may
develop symptoms of empty nose syndrome (ENS) following qualitative functional
changes to the turbinate mucosa consequent to chemocautery, laser therapy, cryosur-
gery, radiofrequency, coblation, and submucosal cauterization, even when the
“observed” amount of turbinate tissue remains fundamentally unchanged.
Does this situation shout for some functional testing of nasal physiologic mech-
anisms as part of routine “preoperative” patient evaluation?
Recall Lord Kelvin, “. but when you cannot measure it, when you cannot ex-
press it in numbers, your knowledge is a meagre and unsatisfactory kind; it
may be the beginning of knowledge, but you have scarcely in your thoughts
advanced to the state of Science, whatever the matter may be.”
The question arises, how does damage to the nasal mucosa generate each and
every one of the various protean symptoms seen in ENS?
A recent computerized tomography (CT) study examining the volume of turbi-
nate tissue remaining in ENS patients versus a control group demonstrated a signif-
icant correlation between symptoms of nasal dryness, facial pain, posterior nasal
“drip,” and nasal discharge with small inferior turbinate volume (size) compared
with normal sized (volume) turbinates in the control group. The study also identified
an impaired quality-of-life for these ENS patients and discovered that the mean time
to diagnosis of ENS from the time of initial surgical turbinate reduction was over 6.5
years.28 That delay or latency time can be measured in years, which is similar to the
findings of others.2,18 Despite these valued findings, currently there are no objective
criteria indicating the amount or volume of turbinate tissue removal or residual
mucosal remnants that specifically induces ENS.
Regarding the symptom of pain, some researchers have hypothesized that a large
contributor of pain seen in ENS is neural damage, akin to “phantom limb” pain, in
the turbinate tissue (parenchyma) with abnormal neural regrowth.31 The support for
this reasoning comes from studies demonstrating the absence of trigeminal re-
sponses in ENS patients, localization of nerve growth factor to the turbinates, and
the abundance of mechanoreceptors, thermoreceptors, and nerve endings in the nasal
cavity.38e40 Nerve injury, secondary to resection trauma, may result in a neurogenic
pain syndrome, “Phantom Turbinate”, likely due to sprouting of pain (A) fibers after
a traumatic injury.41 The simple alteration in degree and type of sensation may
be enough to create a “different” and “bothersome” sensation for the patient that
continues as a constant and persistent irritant.
A substantial decrease in nerve growth factor or paucity of sensory receptors
could result in the diminished sensation of airflow.39 Studies have shown that the lin-
ing of the nasal vestibule is more sensitive to airflow than any other region of the
nasal cavity.40 Since a turbinate procedure reduces the amount of viable and func-
tioning tissue, the sense of stuffiness or difficulty breathing experienced by most
ENS patients may be in part explained by the damage to trigeminal nerve endings
 Pathophysiology of the empty nose syndrome (ENS) 59

and the decrease of growth mediators.19 In ENS, there is disruption of the normal
nasal aerodynamics. Physiological studies have shown that lung volumes are
expanded with increased nasal resistance, but with reduced nasal resistance, as in
ENS or with mouth breathing, lung volumes are decreased.40
Computational models have demonstrated that surgery disrupting turbinate tis-
sue clearly causes changes to nasal airflow from an evenly distributed normal airflow
over the entire nasal cavity to an abnormal uneven airflow distribution with minimal
mucosal contact.41e43 Given the fact that patients experiencing ENS have wider
nasal passages with decreased oronasal resistance, as their lung volumes and, indi-
rectly, arterial oxygenation is decreased, after turbinate reduction, results in disor-
dered breathing and a sense of suffocation.
Why would this sense of suffocation occur? Because the nose normally creates
optimal resistance and efficient air-conditioning, adjusting inspired air to allow for
optimal warmth (temperature) and moisture (humidity) permitting optimal exchange
of carbon dioxide and oxygen at the alveolar level, removal of the middle and infe-
rior turbinates reduces the efficiency of these essential functions.44e48
Ten ENS patients studied at the University of Ulm in Germany demonstrated
lower air temperatures at the nostrils, and lower absolute humidity throughout the
nasal cavity, compared to controls.49 The disturbed airflow and the reduced ability
to warm and humidify the inspired air could explain the crusting and the sensation
of dryness in these patients. Moreover, breathing is adversely affected by the
inability to adjust the temperature and humidity of the inspired air due to the naso-
pulmonary reflex, afferent nerve impulses in the trigeminal nerve with efferent nerve
impulses in the vagus nerve, which is elicited when temperature-sensitive mucosal
nerve endings are activated, producing bronchospasm in response to dry and or cold
air.50,51
There are known physiologic and pathologic conditions that have a direct or in-
direct impact on nasal aerodynamics. These factors, combined with the effect of a
wider nasal airway on airflow after a turbinate procedure, may allow understanding
as to why some patients develop ENS and others do not. The relationship between
nasal form and function is one such consideration. Studies have shown that airflow
characteristics vary from person to person based on anatomic variables such as
nostril orientation (shape), turbinate configuration, overall nasal airway length,
and internal nasal valve area dimensions.52e56 Since individuals with different
nasal geometries such as the long, narrow high-arched (leptorrhine) nose compared
to the short broad (platyrrhine) nose may have completely different experiences af-
ter turbinate reduction resulting from variations in turbulence and airflow rates,
which ultimately determine the amount of airemucosal contact. However, nasal
anatomy may only be relevant in certain climates. Payne pointed out that ENS
seems to occur in certain geographic regions more frequently than others.55 Given
the important air modifying (adjusting temperature and humidity) function of the
nose, patients with certain nasal anatomy undergoing a turbinate reduction proced-
ure would have a different outcome depending on their specific geographic
location.
60 CHAPTER 3 Pathophysiology of the empty nose syndrome (ENS)

Other important factors related to the development of ENS concern the altered
airflow dynamics secondary to portions of functioning turbinate tissue (if any)
remaining after surgical resection in addition to the presence of any underlying dis-
ease process.56 For example, an underlying disease process such as allergic rhinitis
could mitigate the effects of turbinate loss due to persistent hypertrophy or an
increased ability to warm or humidify inhaled air.56,57 Another contributing factor
to the development of ENS is atrophy of the nasal mucosa from chronic inflamma-
tion. A recent study presented patients with normal CT scans prior to inferior turbi-
nectomy only to have mucosal thickening with maxillary and ethmoid sinus opacity
on CT scans postoperatively.58 The resultant mucosal thickening was independent of
sinusitis. Specifically, patients with unilateral sinusitis showed no difference in
mucosal thickening between the affected and unaffected nasal cavities, whereas pa-
tients with ENS had increased mucosal thickening ipsilateral to the operated side.59
The nasal mucosal changes after intervention may be secondary to disruptions in
airflow dynamics with or without mucosal inflammation resulting in squamous
metaplasia. In terms of airflow dynamics, research has shown that, in rabbits with
one nostril surgically closed, increased airflow in the open nostril leads to repeated
cycles of ciliary damage and repair.59 In patients with a “deviated” nasal septum, the
nostril with increased airflow often becomes inflamed and shows impaired mucocili-
ary clearance with an associated decrease in glandular acini density.60 It is well
documented that chronic inflammation leads to metaplasia, changing the normal res-
piratory epithelium to a nonciliated squamous epithelium.18,60 Intranasal biopsy re-
veals squamous metaplasia from an ENS patient seen in our practice, Fig. 3.1.

Intranasal Biopsy – 40x

Ciliated, columnar Squamous mucosa

mucosa
FIGURE 3.1
On the left, normal ciliated (arrow) columnar respiratory epithelium of the nasal mucosa.
On the right, squamous metaplasia of the intranasal mucosa often seen in patients with
the “empty nose syndrome.”
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
 Pathophysiology of the empty nose syndrome (ENS) 61

Damage to normal pseudostratified ciliated respiratory nasal mucosa can lead to

squamous metaplasia, which in turn inhibits normal nasal defensive and respiratory
function due, in part, to disturbed nerve endings contributing to the diminished
airflow sensation frequently reported by ENS patients.56
Moreover, since the mucociliary apparatus is destroyed and replaced by squa-
mous metaplasia, bacteria can flourish and multiply, no longer swept away by phys-
iologic ciliary action, thereby accounting for the malodorous (fetid) nasal discharge
experienced by many ENS patients. While most of the symptoms of ENS are under-
stood based on disturbed physiology and explained in the existing literature, the pro-
found psychological comorbidities seem less explainable.
Payne speculates that ENS “could be likened to other phenomena where there
seems to be a correlation between psychosocial distress and disease tolerance,
such as tinnitus” or that it could be the result of a preexisting “nasal neuropathy”
that is exacerbated by a turbinate procedure.55 It may be useful to test some of
the proposed ideas, such as giving ENS patients who experience facial pain a trial
of gabapentin as Payne advises; however, more data must be gathered on psycholog-
ical factors. As mentioned previously, the Mayo group found that 52% of their 242
patients experienced depression established on the Minnesota multiphase personal-
ity inventory (MMPI) or with psychiatric evaluation.18 Often these patients feel a
loss of control in their lives and psychological depression ensues. The emotional is-
sues need further exploration to better understand how to treat and support these pa-
tients.61,62 To add affront to grievance, patients have regularly informed us that they
were callously dismissed by their treating surgeons; frequently told that their phys-
ical problems were psychologically based. These denials of a patient’s suffering are
grim verdicts for our patients to both hear and digest which often exacerbates their
psychological distress heightening their determination to find a specific medical or
surgical resolution or press for a tangible explanation for their desolation.
 CHAPTER

Treatment options for ENS

4
1. Introduction
A. Medical
B. Surgical
C. Preventing empty nose syndrome (ENS)
Unfortunately, currently there are no curative or even restorative therapies for
ENS.
Realistic management is obliged to provide emotional support by compassionate
attentive listening along with controlling and relieving as many of the patient’s
debilitating symptoms as feasible. Available treatments range from conservative
medical measures to surgical interventions, although nothing that we know of today
can renew, restore, or recreate the damaged or resected nasal mucosa. Short of stem
cell rejuvenation the question remains, how do you create a new and functional nasal
turbinate? Hope nonetheless exists that research in the realms of stem cell and tissue
engineering will deliver potential future possibilities for our patients. Prevention is
always the most prudent choice, of course.

1.1 Medical
Evidence in the literature plus our own experience suggests that certain medical
treatments are enormously effective in reducing some of the distressing nasal symp-
toms, especially the crusting seen in almost all of these patients. Topical moistur-
izing and malodor control agents, including oil of sesame with rose geranium,
which we have used for many years has been useful in helping ease a patient’s
discomfort.18 Manuka honey* which we have not used may offer promise based
on the recent, 2017, publication from the Department of Otolaryngology-Head
and Neck Surgery, University of Washington, Seattle, Washington noted below.
* Lee VS, Humphreys IM, Purcell PL, Davis GE. Manuka honey sinus irrigation for the treatment of
chronic rhinosinusitis: a randomized controlled trial. Int Forum Allergy Rhinol. 2017 Apr;7(4):365e372.
doi: 10.1002/alr.21898. Epub 2016 Dec 9. PMID: 27935259

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Copyright © 2024 Elsevier Inc. All rights reserved.
64 CHAPTER 4 Treatment options for ENS

“Conclusion: In patients with active chronic rhinosinusitis (CRS) and prior sinus
surgery, both Manuka honey (MH) and saline improved outcomes, but there was
no statistically significant difference between these groups. However, in the subset
that did not receive oral antibiotics/steroids, culture negativity was statistically
better on MH, suggesting that MH alone may be effective for acute exacerbations
of CRS.”
The work of Brown and Graham clearly demonstrated that positive pressure nasal
irrigations, although underutilized, can be very effective, especially the finding that hy-
pertonic saline irrigations are superior to isotonic saline in reducing symptoms. Nasal
irrigation (lavage), using a bulb syringe is a pressure method, a “power” wash, that is
more effective compared to the nebulizer (spray) method to introduce the irrigation
solution especially when mucociliary transport mechanisms are disrupted.63 Nasal
irrigation (lavage is more successful than sprays) is effective by physically removing
thickened mucus debris (crusts), bacteria, and the inflammatory mediators, which can
interfere with normal mucociliary (ciliary beat frequency) activity.63
Table 4.1 summarizes the nasal mucosal moistening agents used in the medical
management of patients with ENS and other instances of primary and secondary
atrophic rhinitis.
A useful nasal lavage solution (home recipe) as suggested by Brown and Graham
from the University of Iowa is presented in Table 4.2.
Saline irrigations with and without antibiotics, most notably Wilson’s solution
(80 mg of gentamicin a liter of saline), is often helpful. Wilson solution is first uti-
lized as a 30-cc lavage, not nebulized, three times daily and as symptoms improve
reduced to twice daily, then once daily, or on alternate days as necessary. The tem-
porary reversible use of cotton obstruction of the nasal cavity has been helpful in
moisturizing the nasal mucosal interior while providing some increased resistance
to breathing. This strategy has been helpful for some of our patients in the past.

Table 4.1 Nasal mucosal moistening agents.

A. Nasal lavagea (“power washing” is superior to nebulization) with saline solution
1. NaCl hypertonic solution (superior to isotonic solution)
B. Nasal sprays
1. Dexpanthenol 5% for “Rhinitis Sicca”
2. Liposomalb for “Rhinitis Sicca”
3. Sesame oil with Rose Geraniumc (lubrication and odor control)
50 cc Sig. 2 sprays each nostril bid
a
Note: In general, nasal lavage is superior to nasal spray for the removal of crusts, debris, bacteria,
inflammatory mediators and introducing topical nasal medication(s) in ENS patients.
b
Note: Based on work of: Hahn C, Böhm M, Allekotte S, Mösges R. Tolerability and effects on quality of
life of liposomal nasal spray treatment compared to nasal ointment containing dexpanthenol or isotonic
Na Cl spray in patients with rhinitis sicca. Eur Arch Otorhinolaryngol. September 2013;270(9):2465e72.
c
Note: Based on the Mayo Clinic pharmacy proprietary formulation, Rochester, Minnesota.
 1. Introduction 65

Table 4.2 Nasal lavage solutions (home recipe) from the University of Iowa.
Liquid Salt Baking soda Final tonicity
Four cups (1 quart) H2O BOILED 5 Min 1 1/2 tsp. None. 0.9%
Modified from: Brown CL, Graham SC. Nasal irrigation: good or bad? Curr Opin Otolaryngol Head Neck
Surg. 2004;12:9e13.
“Home recipes” versus manufactured powders/solutions
The section on Practical points is quoted directly from Brown and Graham. (63)
“Solutions too cold or too hot are not ideal. The careful use of microwaves can be helpful. Nasal
irrigations can be performed over a kitchen sink, over the bathroom basin, or in the shower. The shower
provides a ready source of nonsterile water at a chosen temperature. Patients administer the solution
with a bulb syringe after instruction by the nursing staff. Demonstrations and handouts are provided.” (63)
This “Home recipe” (Table 4.2) generally consist of boiled water, which is cooled before use, mixed
with nonionized salt. Table salt is generally not recommended because it contains additives. Baking
soda may be used to buffer the solution but is not essential. Solutions are generally kept in the refrig-
erator before being discarded after several days. In a recent study, a randomized, controlled trial looking
at patients with two episodes of acute sinusitis or one episode of chronic sinusitis per year for 2
consecutive years. Fifty-two patients received hypertonic saline, whereas 24 patients did not receive
any irrigations. When using hypertonic nasal irrigations, improvements in quality-of-life and overall
symptom severity scores were statistically significant. Steroid nasal spray use was also decreased.

Evaluation at a pain management center with therapeutic use of pain medications

administered by those physicians expert in pain control could be considered for pa-
tients suffering facial pain and headache.
Psychological support with a compassionate respectful referral to a psychiatrist
or other interestedmental health professionals has been valuable inmanaging the
anxiety and depression experienced by a sizable share (over 50%) of these
patients.18,62
Offering a summary of the treatment strategies and diagnostic tools for the ENS,
Gill and associates observed that, “Nasal humidification, patient education, and
treatment of possible concomitant medical conditions (e.g., depression) constitute
first lines of treatment.”33

1.2 Surgical
The goal of surgical procedures has been to reduce ENS airway symptoms by narrowing
the nasal cavity in an attempt to reconfigure nasal airway anatomy and reestablish
“normal” nasal airway resistance. A diverse assortment of materials has been attemp-
ted to reestablish a “normal” nasal airway with varying degrees of success. That’s the
challenge, how to create a turbinate analog? One of the answers was the use of inject-
ables such as hyaluronic acid (HA) and autologous stromal vascular fraction (SVF).
Recently, Modrzy nski injected HA submucosally resulting in an increased sensation
of nasal airflow and decreased crusting and dryness for less than a year (n ¼ 3).64
Since the effects of HA are temporary, repeat injections are required to sustain relief.
Caution with injections of fillers must be exercised as vascular obstructive inci-
dents and infections are known complications that could be symptomatically and
emotionally devastating plus painful to the patient. Others have utilized autologous
cartilage grafts from various donor sites including the nasal septum, conchal and rib
cartilage. These autologous septal, conchal, and costal cartilage grafts have been
found, in ENS, to decrease pain (nasal and facial), reduce the sensation of extreme
airflow, lessen nasal crusting, and decrease the feeling of nasal obstruction.18,65 The
66 CHAPTER 4 Treatment options for ENS

cartilage graft donor site comorbidities are a cause for disquiet particularly because
as Jang et al. noted there may not be enough conchal or septal cartilage available to
produce the required volume to reduce the symptoms.65
Recently, a study showed that costal cartilage may be superior to conchal carti-
lage in the treatment of ENSdstatistically significant improved SNOT-25 scores
were obtained for both conchal and rib cartilage implants, and suggested reasons
for this difference included the increased availability, volume, and strength of rib
cartilage as compared with conchal cartilage.65 Allografts of acellular dermal im-
plants have also been shown to be somewhat effective, with noted improvements
in breathing sensation, reduction in nasal crusting, improved sleep, and alleviating
some of the psychological stress including depression or anxiety.19,62,64,65 For pa-
tients experiencing pain, Houser noted that dermal implants are not particularly
helpful.20 Alloplastic implant materials are unproven but have been used for ENS
including: alloplastic implants of Plastipore, hydroxyapatite, Medpor, and beta-
tricalcium phosphate.66e69
A new study comparing silastic with alloderm implants found no significant dif-
ference between the two materials since patients in both groups showed objective
and subjective symptomatic improvement.70 Unfortunately, most of these studies
are limited by small sample size and varied outcome measures. The idea of engaging
regenerative treatments using stem cells as a therapeutic management option for
ENS patients has been considered with two studies showing mixed results. Kim
and colleagues evaluated the effectiveness and safety of the autologous stromal
vascular fraction (SVF) in the treatment of nine ENS patients. Although the SVF
treatments act to decrease the inflammatory cytokine levels in the nasal mucosa, a
single SVF injection was not effective in terms of symptom improvement and patient
satisfaction.71
New research, in 2015, by Xu et al., using adipocyte-derived stem cells (ADSCs)
has provided ENS patients with renewed hope for the future. These ADSCs produce
and secrete cytokines that support tissue growth while dampening mucosal injury.
The nasal mucociliary activity was significantly improved in the 28 ENS study pa-
tients, and there was noted improvement in the symptom of nasal obstruction as tis-
sue inflammation was reduced significantly.72 Further trials, preferably randomized
controlled trials, are clearly compulsory to identify the most practical and useful
regenerative treatment modality for patients with ENS.
Leong performed a literature review of various surgical interventions in which
implanted materials were applied to the nasal sidewalls of ENS patients. He included
eight studies and reported on the aggregate data collected on 128 ENS patients. His
analysis, using the reported SNOT-20 and SNOT-25 scores at 3 months and
12 months posttreatment, found that 21% of patients in the various studies reported
only marginal subjective improvements.73
Since not all surgical interventions resulted in patient benefit, Leong cautioned
and advised us to require larger numbers and lengthier follow-up periods with uni-
form outcome measures before determining the utility of any surgical therapeutic
intervention and before deciding which specific surgical intervention is superior
and most beneficial for the patient.73
 1. Introduction 67

Anecdotally, in our practice, we have seen many patients treated surgically with
implants, at other institutions, who have returned disappointed complaining of
persistent or worsening; escalation of symptoms. Even more unsettling are those pa-
tients who after implant surgery experience intensified and increased psychological
distress. Aggravated anxiety and “nasal focus” have been typically found among pa-
tients whose hopes and expectations are heightened leading into a surgical interven-
tion aimed at reversing or ameliorating the ENS symptoms, only to be disheartened
by the discouraging postoperative outcome. Many ENS patients experience
emotional suffering with abundant anxiety and discernible depression; it is our re-
sponsibility as treating physicians and surgeons to genuinely and sympathetically
counsel our patients, as the “guardians of reality”; not discounting our patient’s
symptoms but listening intently and offering realistic therapeutic options and never
the mirage of “cure.”18,62,73e75
Regarding an update on the treatment strategies for ENS, Gill and colleagues in
2019 stated that, “Although injectable implants to augment turbinate volume show
promise as a therapeutic surgical technique, there is insufficient data to fully sup-
port their use at this time.”76 (Bold italics added) Additional procedures hold prom-
ise and are described in Chapter 11. A comprehensive list of surgical operations are
described in Chapter 11.

1.3 Preventing ENS

In life, as in nasal surgery, especially concerning inferior turbinate surgery, “it’s not
what you take, it’s what you leave behind that matters.”
Regardless of turbinate treatment strategies advocated by some surgeons, it is
clear that the optimal turbinate management lies in the prevention of ENS. It is
our experience and that of others, preservation of the nasal mucosa is the authorita-
tive imperative to elude the catastrophic calamity of ENS. Unfortunately, it is un-
known, at the present moment, as to the precise amount of nasal mucosa and
submucosa that must be preserved during intranasal turbinate procedures to prevent
ENS. As a consequence, we should always minimize turbinate manipulation with
attendant mucosal and submucosal damage, including radical excision of the turbi-
nates only when absolutely obligatory. We all realize that radical turbinectomy is
indispensable for inverting papilloma, certain malignant tumors and may be requi-
site for teenage boys with juvenile angiofibroma.
Our maximum turbinate preservation position has been ferociously argued
against by a cavalcade, in our opinion, of “cavalier” surgeons two of whom are
well-known proponents of total turbinectomy from their writings, Eugene Courtiss,
MD and Dov Ophir, MD. One of us (EBK) has had the opportunity to publicly
debate, each one on separate occasions, challenging their denial of any explicit or
pivotal relationship between total inferior turbinectomy, with its cataclysmic phys-
iological wreckage, and its proficient propensity for precipitating ENS.
How often is the impact of altering nasal breathing mechanics, injuring the nasal
defenses, damaging the nasal cycle and a plethora of nasal reflexes, or the likelihood
of inducing a posttraumatic amputation pain syndrome considered before nasal sur-
gical intervention? How often are objective nasal functional testing methods
68 CHAPTER 4 Treatment options for ENS

available or obtained prior to or following nasal surgical intervention in our “modern

21st century era”? We do not know the answer to these questions; however, if the
literature is accurate, we reason that nasal physiologic measurements prior to nasal
surgery are quite infrequent in our country. Because of the unique variability of a
given individual’s response or a person’s “host resistance” to nasal mucosal trauma,
which is arbitrary, unpredictable, and unmeasurable, surgery on the turbinates, espe-
cially the inferior turbinate, to improve nasal airway breathing, must be very “con-
servative” inflicting the “minimal” trauma and should be directed to the head of the
inferior turbinate, which is the posterior portion of the internal nasal valve area, the
most critical site for nasal breathing.
Since none of the current ENS treatment options can resolve all of the symptoms
of ENS nor can resected or damaged nasal mucosa (“organ of the nose”) be replaced,
repaired, or restored. Based on our current understanding of the iatrogenic nature
and the pathophysiology of ENS, it is clear from the literature, linked with our
own involvement with hundreds of ENS cases, for more than a quarter-century,
that wide-ranging extensive evidence assuredly exists that total inferior turbinate
resection for nonmalignant disease should be condemned, in concert with Moore
et al.,2 and that nasal mucosal trauma must be avoided at best or minimized at least.
Because it is unclear the degree of nasal mucosal or submucosal injury in any
particular individual that will significantly disturb nasal function(s), especially
breathing (respiratory) and defense, which are capable of producing ENS; we exer-
cise remarkable restraint when considering turbinate management and offer some
options when managing the turbinates in Chapter 7 The Turbinates-Management.
So, we conclude this section on the prevention of ENS with the repetitive chorus
of Prevention, Prevention, and more Prevention of iatrogenic ENS through the
avoidance of “excessive” turbinate reduction, which remains an imperative in pre-
venting the plague and torment of ENS. Finally, in a thoughtful 2019 paper by
Gill and colleagues discussing the pathophysiology of ENS and reviewing the med-
ical and surgical treatment approaches for ENS patients, they concluded that the pre-
vention of iatrogenic ENS “. is through avoidance of excessive turbinate
reduction .”76 (Bold italics added)
 CHAPTER

The turbinates—an
overview
5
1. Historical perspective*
To the best of our knowledge, it was a New Yorker, William M. Jarvis, MD who in
1882 described three cases of utilizing a snare to affect a partial turbinectomy in
which he stated: “I have selected two cases of posterior turbinated hypertrophy
and one of anterior hypertrophy from a number of the kind, as best illustrating
certain points to be fully considered in my conclusions. The Écraseur** used by
me to remove these growths was shown to the American Laryngological Association
in 1880.” In his description, he said that: “I removed the gelatinous polyps from both
sides of the nose using the écraseur. I then snared postinferior turbinated hypertro-
phy occupying the left postnasal opening and drew the wire loop tightly around the
growth.”77
*Authors note: We have chosen to be historically inclusive, perhaps excessively
expansive, at the risk of being “overly comprehensive” in presenting the “other
side” of the “turbinate debate” in their own words from their own writings,
which supports our preference for conservative tissue sparing principles when
compared to aggressive tissue resection with seemingly little regard for the func-
tional, physiologic, activities of the nasal respiratory mucosa, including the
epithelial layer and the deeper submucosal stromal tissues. To fathom the depth
of the acerbic aspects of the “turbinate debate,” especially regarding inferior
turbinate management, we believe this in-depth historical perspective is required,
virtually commanding.
** Note: E´craseur translated from the French language as “crusher.”
At the dawn of the 20th century, most surgeons were promoting total inferior tur-
binectomy not only for nasal airway obstruction but astoundingly also for hearing
impairment and tinnitus. T. Carmalt Jones presented at a meeting of the British Med-
ical Association and notes from that meeting were presented in the distinguished and
dignified medical journal The Lancet in 1895 which cited his presentation as
follows:

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70 CHAPTER 5 The turbinates—an overview

“Removal of hypertrophied inferior turbinals and moriform growths should be

practiced in cases of deafness and tinnitus where the auditory nerve was in a
healthy condition.” He had operated in upwards of 500 cases. Notes were read
of twelve cases of deafness or tinnitus in which turbinotomy had been performed.
“Eleven of these were cases of deafness and tinnitus combined. Relief to both con-
ditions was afforded in eight cases; slight relief to deafness only in one. In two
there was no relief at all. A discussion followed.”78
Two months later at the Fifth International Congress of Otology, another physi-
cian with the identical surname as T. Carmalt, Dr. MacNaughton Jones presented a
paper which was also covered in The Lancet and titled: “Turbinale Hypertrophy and
its Deafness Relations, especially with regard to Operation Turbinotonrie.” This
chronicle was translated from the French and was introduced by Dr. MacNaughton
Jones and was respectably described in the journal as follows:
“Dr. MacNaughton Jones gave a masterly review of the subject as dealt with by
previous otologists, and summed up by some of his own conclusions: “Turbinal
hypertrophy must be regarded as a serious complication of deafness and the
cognate aural affections; in those cases, in which it precedes the aural symptoms
we may justly regard it as being their principal cause.” Dr. Jones resumes:
“In all cases in which this hypertrophic change is discovered active therapeutic
measures, of which galvano-cauterisation is the chief, ought to be put in practice
to reduce it. Turbinotomy is indicated and ought to be reserved for those cases in
which, whether in consequence of the bulk or of the nature of the growth, it is vain
to expect improvement from any other treatment.”79
Of course, turbinate enlargement or “hypertrophy” is neither the cause nor a
complication of hearing loss. Fortunately, and for the most part, dazed blunders
and egregious errors in thinking by esteemed experts, for the most part, have reme-
died itself through scientific studies, since the late 19th century.
A mere five years later, in 1900, CR Holmes published an article in The New York
Medical Journal where he acknowledged the status of the nose as a significant or-
gan system and that minimal resection of the inferior turbinate was superior to
“extensive destruction,” which “generally leads to dryness of the pharynx.” Which
we can probably assume that “dryness of the pharynx” is a form of atrophy, a sec-
ondary atrophic rhinitis.80 (Bold italics added)
Dr. Holmes astutely continued:
“The object of every operation is to restore as nearly as possible the parts to a
normal condition, and in operating we should not only consider the immediate
but also the remote effects. In operating upon the nose, we must remember
that it is a very important organ, whose function is to partly filter, moisten,
and warm the air before it enters the pharynx, larynx, and lungs. Too extensive
destruction these bodies generally leads to dryness of the pharynx and inability
of the patient to effectually expel the nasal secretion by forcible blowing of the
 1. Historical perspective 71

nose, which is another source of annoyance.” “In all cases, aim to remove as
little of the edge of the inferior turbinated as is consistent with the restoration of
sufficient breathing space, and save as much of the anterior end of the bone as
possible.”80 (Bold italics added)
The renowned rhinologist, Dr. Otto T. Freer of Chicago, in the early part of the
20th century, recognized along with CR Holmes that radical procedures of the infe-
rior turbinate were both irresponsible and unwise. In a paper written in 1911, Freer
indicated that:
“In order to avoid the creation of the bad stump embodying the objections
mentioned and with the idea of sufficiently preserving the physiologic function
of moistener of the inspired air, possessed by the turbinated body, I gradually
devised the operative method here described and have employed for several years
with great satisfaction. It reduces the turbinated body to any size desired and in-
sures covering of the cut surface by a flap.”81 (Bold italics added)
Dr. Freer observed the introduction of radical turbinate operations replacing the
unpredictable results with cauterization, and yet he reports that he has never seen a
case of atrophic rhinitis:
“Rhinologists, therefore, have in a large measure abandoned cauterization for
intumescence and have adopted the more radical procedure turbinotomy instead
the turbinate being wholly almost cut away with the saw, scissors, or punch. I
have not, however, after turbinotomy performed even in this crude manner, found
the permanent chronic scabbing described by some authors and have found that
in time the stump always heals over smoothly; nor have I ever seen atrophic
rhinitis as a consequence of even the complete removal of an inferior turbinate,
atrophic rhinitis being a distinct pathological process which cannot be surgically
created.”81 (Bold italics added)
Despite the brilliant observational powers of the dazzling Otto T. Freer, his state-
ment that atrophic rhinitis cannot be surgically created likely refers to ozena, as we
now know, from hundreds of cases that secondary atrophic rhinitis can be “surgically
created” secondary to radical excision that may not appear for some many years after
the initial surgery.2e4,18e28 Freer proceeded to describe his technique for excising
the conchal bone while preserving the mucosa with an inferior turbinate mucosal
flap. This mucosal flap preservation occurs all the while performing a longitudinal
resection of as much of the conchal bone as possible at its root. Sadly, Freer does
not offer any patient data and concludes the paper with:
“The longitudinal resection I have described here has been successfully employed
by me for a number of years and I recommend it as a tried and completed
procedure.”81
In 1914, just a few years after Dr. Freer’s inferior turbinate conchal bone excision
with mucosal flap preservation, Dr. Albert Mason of Georgia also recognized along
72 CHAPTER 5 The turbinates—an overview

with CR Holmes the requisite prerequisite for preserving the physiologic function
of the nose as he wrote a plaintive plea for conservation of the inferior turbinate
mucosa:
“In the first place, ‘damage to mucous membrane’ is certainly much greater in
turbinotomy than in submucous resection. In the former, a large area is
completely removed, while in the latter, the linear incision heals with practically
no destruction of the nasal mucous membrane. Furthermore, the mucous mem-
brane covering the inferior turbinate is the most important functionating part
of the nose, and for this reason should be left alone, when possible.” (Bold
italics added)
Dr. Mason added that:
“I have also seen a condition resembling atrophic rhinitis follow the removal of
part of the turbinate. Patients, upon whom turbinotomies had been done some
time previously, complain of a dryness of the nose and throat, but have never
seen or heard of a case developing a dryness after a submucous resection.”
“In conclusion, I plead with you, both rhinologist and general practitioner, to
respect the function of the inferior turbinate and to save it when possible to
do so.”82 (Bold italics added)
Obviously, Dr. Mason observed the deleterious consequences of injury to the
nasal mucous membrane of the inferior turbinate resulting in secondary atrophic
rhinitis. Realizing and articulating that the nasal mucous membrane is the most
important functioning portion of the nose obliging preservation. Evidently, even
in the first quarter of the 20th century, enough cases were discussed or reported
that warned the profession of adverse sequelae after an aggressive inferior turbinate
injury with secondary atrophic rhinitis. In addition to secondary atrophic rhinitis,
surgeons had to contend with the terrorizing experience of intraoperative and or
postoperative hemorrhage after aggressive turbinate resections. Dr. Mason reported
that he never detected a case of atrophic rhinitis when only the conchal bone of the
inferior turbinate was removed but the nasal mucous membrane was preserved.82
Dr. William Spielberg of New York City influenced by Freer and Dr. W. Stuart
Low further discussed resection of the conchal bone of the inferior turbinate, with
turbinate mucosal preservation. Dr. Spielberg realized that adverse sequelae could
occur when excessive mucosal tissue of the inferior turbinate is removed. Quoting
directly from his 1924 paper as follows:
“The chief objection to many of the operations as at present performed on the
nasal passages in general and the inferior turbinate in particular for the allevi-
ation of nasal obstruction, is that frequently to much tissue was removed. This
holds true for such operative procedures as cauterization, partial amputation,
or the so-called clipping of the inferior turbinates, the spoke shave operation,
Ballenger’s swivel knife operation, the flap resection operation of Otto T. Freer.
The submucous anterior turbinectomy operation first described by W. Stuart Low
 1. Historical perspective 73

and apparently later (1911) modified, but not very much improved by Freer,
comes closest in the opinion of the writer, to the ideal manner in dealing surgi-
cally with an hypertrophy of the inferior turbinate.” (Bold italics added)
Dr. Spielberg presented details of a limited submucous resection operation of the
conchal bone all the while preserving the nasal mucosa. He presented details
regarding 20 patients (9 females, 11 males) with follow-up from one month to six
months, age range from 16 to 56 years and 19 were pronounced cured while his
last patient’s result was less than cured but nonetheless graded as “good.”83
The eminent otologist Howard House of Los Angeles, California, continued the
tradition of submucosal resection of the inferior turbinate conchal bone with preser-
vation of the precious functional nasal mucosa and submucosa of that same inferior
turbinate.
“The success of this operation depends upon removing the thickened anterior
portion of the inferior terminal bone with a minimum amount of trauma to the sur-
rounding mucosa.”84
Using a postoperative questionnaire in the entire study population (n ¼ 102),
House found complete (100%) relief of nasal airway obstruction in 47 patients
(46%) and 75% relief in 19 patients (18%). He concluded that the majority of pa-
tients (n ¼ 102) who underwent submucous resection of the anterior one-third of
the inferior turbinate conchal bone had a favorable response with 64% of patients
having 75%e100% relief of nasal airway obstruction at 2 years after surgery.
Another 14 patients (14%) had 50% relief of nasal airway obstruction, and 5 patients
(5%) had 25% relief, no relief in 14 patients (14%) while 3 patients (3%) were made
worse. The operation reduced the size of the anterior head of the inferior turbinate
with a minimal of interference to nasal physiology.84
In 1973, Hunter Fry published in the Australian and New Zealand Journal of Sur-
gery an article entitled, “Judicious turbinectomy for nasal obstruction.”85 With that
title one would plausibly anticipate that the “conservative” approach advised by
Holmes,80 Freer,81 Mason,82 Spielberg,83 or House84 would have reached the shores
of the island country Australia, even by an extremely dawdling boat; however, Fry
plunges precipitously and abruptly into total inferior turbinate resection, turbinate
termination by the stealth of steely scissors. The quotation from his work listed un-
der the section titled Technique reads quietly and unassumingly:
“The inferior turbinate is reduced with turbinectomy scissors.”85
Addressing the middle turbinate, he continues:
“The middle turbinate is reduced by Hartman’s conchotome, or sometimes by
Luc’s forceps when there is no room to spare and a septoplasty has not been car-
ried out (which assists exposure of the middle turbinate).”
74 CHAPTER 5 The turbinates—an overview

Fry, in the Conclusions of his paper, writes:

“The operation of surgical reduction of the turbinates has been found to be a most
satisfactory and necessary procedure for the relief of nasal obstruction. It can be
relied on to relieve nasal obstruction and its complications. In the last year post-
operative bleeding has not been a significant problem. The writer has not seen
any cases of rhinitis sicca in his own patients.”85
Of his abbreviated list of 8 references include: 2 “personal communication,” 1
“not published” and symposium (unpublished), 2 text books (1955, 1971), and 2
journal articles (1965, 1970). He never mentions Holmes,80 Freer,81 Mason,82 Spiel-
berg,83 or House84 because, in all likelihood, he was either indifferent or oblivious of
the American literature. Below is the list of references by Hunter Fry in the journal:
Aust N Z J Surg. 1973 Feb;42(3):291e4.
1. Cantor C. (1972), personal communication.
2. Caust, LJ. (1968), “The Surgical Relief of Nasal Obstruction” paper read at
general scientific meeting of Royal Australasian College of Surgeons, Adelaide,
but not published.
3. Caust LJ. (1972), personal communication.
4. Clarke G. (1972), in symposium on “Turbinectomy” at the University Depart-
ment of Otolaryngology, Royal Victorian Eye and Ear Hospital
5. Duouek E. (1971) in Scott-Brown’s “Diseases of the Nose,” Butterworths,
London: 220.
6. Ewert G. (1965), Acta oto-laryng. (Stockh.), Suppl.200 (Complete citation is
added by authors as follows: Ewert G. On the mucus flow rate in the human
nose. Acta Otolaryngol Suppl. 1965; 200:SUPPL 200:1e62. PMID: 14326391.)
7. Thomson ST C, Negus VE. (1955), “Diseases of the Nose and Throat” Cassell &
Co., London: 195.
8. Watkins ABK. (1970), Med J Aust, 1: 382.
(The complete citation is added by authors as follows: Watkins AB. Middle
turbinate headache. Med J Aust. 1970 Feb 21; 1(8):382e4. doi: 10.5694/j.1326-
5377.1970.tb77928.x. PMID: 5439147.)
Unfortunately, Fry, in his turbinectomy assertion, provides neither illustrations
nor any data. He referred to rhinitis sicca as atrophic rhinitis, not making the distinc-
tion between primary and secondary atrophic rhinitis writing:
“To the writer’s knowledge, there has been no hard evidence ever available that
this (rhinitis sicca-atrophic rhinitis) is a sequel of turbinectomy.” Furthermore,
Fry adds: “Rhinitis sicca appears to be a constitutional disease rather than a sur-
gically induced condition.”
Alarming us the most is, how many young surgeons were likely influenced by
this paper written in an esteemed medical journal? (Bold italics added highlighting
our marvel as to which revered reviewers permitted publication of this paper.)
 1. Historical perspective 75

To understand how much has stayed the same in medicine, it benefits to hop on a
proverbial “Time Machine” and voyage back over a century to September 1914
when Dr. Albert Mason of Waycross, Georgia, warned us in his plea for the conser-
vation of the inferior turbinate as follows:
“.I have also seen a condition resembling atrophic rhinitis follow the removal of
part of the turbinate.”82
In his final remarks, Dr. Mason wrote:
“In conclusion, I plead with you, both rhinologist and general practitioner, to
respect the function of the inferior turbinate and to save it when possible to
do so.”82 (Bold italics added)
Obviously not every experienced surgeon was listening, reading, or grasping the
medical and surgical literature of the day, or for that matter, approximately a com-
plete century of pertinent medical literature.
In a wide-ranging historical review, spanning more than a century (actually over
the past 130 years) of treating inferior turbinate pathology, with 13 various tech-
niques, Hol and Huizing updated the profession in the millennial year of 2000
with their extensive bibliography (141 references) in the journal Rhinology outlining
both borders of the debate immediate to the inferior turbinate.25 Regarding the
debated treatment disagreements, they thought that:
“Some authors consider turbinectomy as an appropriate method, while others
condemn it as too aggressive and irreversibly destructive. In the light of these
and other controversies, this article reviews and evaluates the literature on the
surgical treatment of hypertrophied turbinates.”25
And after their intensive and thoughtful critical analysis, Hol and Huizing
declared:
“Our review of the literature revealed a serious lack of qualified studies. Research
meeting the criteria for a prospective comparative randomized surgical study is
extremely rare. Studies that meet all the criteria of a prospective comparative sur-
gical study do not exist, with the notable exception of the recently published study
by Passali et al. In our opinion, the purpose of surgically reducing the inferior
turbinates should be to diminish complaints while preserving function. From
that perspective, it seems that electrocautery, chemocautery, (total and subtotal)
turbinectomy, cryosurgery, and laser surface surgery should not be used, as these
techniques are too destructive. Intraturbinal turbinate reduction (intraturbinal
turbinoplasty) would seem to be the method of choice.”25 (Bold italics added)
76 CHAPTER 5 The turbinates—an overview

Their recommendation of intraturbinal turbinoplasty was based on both their

literature review and extensive clinical experience in concert with understanding
the importance of preserving the physiology of the inferior turbinate. Hol and Hui-
zing synthesized and summarized the function of the inferior turbinates beyond the
warming and humidification of the inspired air to include its significant inspiratory
breathing (respiratory) function of providing inspiratory resistance as follows:
“First of all, they (inferior turbinates) contribute to inspiratory resistance, which
is necessary for normal breathing. The greater the nasal resistance, the greater
the negative intrathoracic pressure needed for inspiration. Greater negative pres-
sure, in turn, enhances pulmonary ventilation and venous backflow to the lungs
and the heart (Butler, 1960; Haight and Cole, 1983).* This is what we would
like to call the ,‘resistor function’ of the turbinates. Secondly, as part of the valve
area, the inferior turbinate helps change the inspiratory lamellar airstream into a
turbulent flow. Turbulence in the outer layers of air increases the interaction be-
tween air and nasal mucosa. Humidification, warming up, and cleansing of the
air are thus enhanced. Thanks to their large mucosal surface and extensive blood
supply, the inferior turbinates play a major role in this process. This role may be
called the ‘diffusor function’ of the inferior turbinates. Finally, they (inferior tur-
binates) are essential to the nasal defence system (mucociliary transport, humoral
and cellular defence). All of these functions require a large amount of normally
functioning mucosa, submucosa, and turbinate parenchyma.”25 (Bold italics
added)
*References noted: Butler J (1960) The work of breathing through the nose. Clin Sci
19:55e62, Haight JSJ, Cole P (1983) The site and function of the nasal valve. Laryn-
goscope 93:49e55.
Hol and Huizing considered the anterior portion of the inferior turbinate head
(the posterior portion of the internal nasal valve area) to be a frequent site of nasal
airway obstruction.25 We agree with these observations along with their thinking,
which harmonizes with the pioneering landmark work of Haight and Cole previously
referenced.5
Resection of the anterior portion of the inferior turbinate (anterior turbinectomy)
was advocated by numerous other surgeons.86e88 In the early 1980s, Richard Mabry
from Dallas, Texas, introduced the term “turbinoplasty,” aptly named, by reducing
both the submucosal parenchyma and conchal bone of the inferior turbinate all
the while preserving the overlying pseudostratified ciliated respiratory epithelium
designed to preserve physiological nasal function.89e91
Turbinoplasty92e94 fleetingly held sway until another dark age descended upon
the rhinologic panorama with the reintroduction of turbinate trauma by a number
of enthusiastic practitioners of total turbinectomy who we unashamedly term turbi-
nate traumatologists. Turbinectomy after falling from grace was resurrected and rec-
ommended by these traumatologists, initiating a new reign of turbinate
 1. Historical perspective 77

terror.85,87,95e116 Claiming that adverse consequences of total turbinectomy had

never been recognized or documented, Courtiss and Goldwyn (1984) stated that:
“Fears for dry nose syndromes are unfounded.”97
Obviously, these authors were either indifferent or unaware of their American
compatriots Holmes (1900),80 Mason (1914),82 Spielberg (1924),83 House
(1951),84 and Mabry (1982).91
Ophir et al. after performing total turbinectomy in 150 patients followed for 1e7
years (mean 2.5 years) trumpeted that:
“Postoperative complications are minimal, and no patient complained of crusts,
dryness, or foul odor.”100
Seven years later in 1992, Ophir et al. affirmed that after interviewing and exam-
ining 186 inferior turbinectomy patients followed for 10 to 15 years (mean 12.3
years) that:
“Atrophic changes of the nasal mucosa and chronic purulent infection were not
observed in any of the patients.”102
These were the sorts of statements spread by some
sides,81,85,87,96,97,100e103,105,106 which were disputed by the other side who witnessed
and described long-lasting signs and symptoms of persistent nasal airway obstruc-
tion, crusting, dryness, and postoperative posttraumatic pain syndromes in a multi-
tude of other patients.2e4,9,18,19e21,24,25,28,110,112,114e116,118 With the turbinate
argument ablaze, Hol and Huizing, after examining the evidence, offered their
cool and somewhat detached diktat:
“In our opinion, there is no justification for performing a total or subtotal turbi-
nectomy in patients with a hypertrophic inferior turbinate. Turbinectomy is not
compatible with the goal of ’preservation of function’. Turbinectomy is irrevers-
ible and deprives the nose of one of its important organs. There is thus no place
for this technique in modern functional nasal surgery. There are more conserva-
tive surgical methods to achieve the desired effect.”25
Hol and Huizing also noted that intraoperative and postoperative hemorrhage
was a significant issue associated with total inferior turbinate resection that defi-
nitely required reporting.25,85,95,115,116
As it is impossible to be totally objective, so in the spirit of fair-mindedness, we
have taken the liberty of presenting the contrary viewpoints using their own words.
The tenor and tone of the turbinate debate is clearly conveyed with several exam-
ples from exceptionally influential surgeons, including some particularly persuasive
78 CHAPTER 5 The turbinates—an overview

plastic surgeons, charismatic and forceful in expressing their opinions abstracted

from their papers.
Courtiss (1978) and colleagues stipulated that:
“We report a series of 88 patients in whom 119 obstructing inferior nasal turbi-
nates were resected for airway obstruction, and who have been followed for
3 months to 3 years. The airways were consistently improved and, to date, there
have been no undesirable sequelae”95 (Bold italics added)

In a follow-up paper, Courtiss and Goldwyn (1983) specifically stated:

“In 1977, we advocated partial resection of the inferior turbinates when turbine
hypertrophy was the cause of nasal airway obstruction. The purpose of this
communication is to present a follow-up of the 88 patients and, in particular,
to assess any adverse effects that might have occurred.”96
Those authors determine as follows:
“On the basis of these findings, we conclude that our original recommendations
and observations are correct: Partial resection of the inferior turbinate is proper
treatment if that is the cause of airway obstruction.”96 (Bold italics added)
 1. Historical perspective 79

From this 1984 “Nasal Physiology” paper by EH Courtiss, TJ Gargan, and GB

Courtiss,97 note that their Fig 10 announces a left internal nasal valve obstruction.
We raise the following two issues. First, the left internal valve obstruction is not
observable on this photograph. Second, the photograph is shown upside down, of
course, adverse mishappenings may occur even after corrected galley proofs are sub-
mitted to a journal, otherwise knowledge and complete understanding of the anat-
omy involving the internal nasal valve may possibly be deficient. Their section on
nasal reflexes contained a meager 5 sentences, which is certainly not an all-
encompassing discussion of nasal physiology plus the paper lacked information
regarding any of the extensive and critical defensive functions of the nose. Then
in 1990, Courtiss and Goldwyn wrote:
“On the basis of our examination of these 25 patients, all of whom had bilateral
inferior turbinate subtotal resection performed at least 10 years ago, we believe
that this kind of resection is the treatment of choice for airway obstruction due to
hypertrophy of the inferior turbinates and that fears of dry nose syndromes are
unfounded.”98 (Bold italics added)
It is astounding to us that this 1990, 10-year follow-up paper by Courtiss and
Goldwyn seen in Table 5.1 on page 153 of their paper, they recorded 2 of 23 patients
with dry nose after surgery and 5 of 20 patients with crusting after surgery, that is a
crusting complication rate of 25%. (Bold italics added) What’s even more perplex-
ing is that in the first line of their discussion these authors state:
“We have not observed a dry nose syndrome in any of these 25 patients, all of
whom were followed for over 10 years.”98 (Bold italics added)
80 CHAPTER 5 The turbinates—an overview

That statement of certitude certainly conflicts with their printed table number II
(our Table 5.1 below). We wonder how they define a dry nose after surgery versus a
dry nose syndrome as there’s nothing in their paper that makes the distinction or ad-
dresses these discrepancies.

Table 5.1 Patient assessment of symptoms before and after surgery.

Before surgery After surgery
Yes No Yes No

Runny nose 4 21 6 19
Dry nose 4 21 2 23
Crusting 3 22 5 20
Postnasal drip 6 19 7 18
Nose bleeds 5 20 7 18

Table 5.1 from: Courtiss EH, Goldwyn RM. Resection of obstructing inferior
nasal turbinates: a 10-year follow-up. Plast Reconstr Surg. 1990;86:152e4.98
Another formidable contributor leading the charge headlong into the turbinate
debate was Dr. Dov Ophir who also championed and advocated aggressive turbinec-
tomy that we find appallingly atrocious. He and his colleagues wrote in 1985:
“Eighty percent of the patients reported improvement in nasal breathing, and 14
(27%) of the 51 patients who suffered from nasal drainage preoperatively re-
ported that it had stopped after the operation. Of the 39 patients who had anosmia
preoperatively, 46% reported the restoration of their sense of smell. Postoperative
complications are minimal, and no patient complained of crusts, dryness, or
foul odor.”100 (Bold italics added)
Several years later in 1990, Dr. Ophir proclaimed that:
“Total inferior turbinectomy was carried out in 38 patients who complained of
nasal obstruction following rhinoplasty or rhinoseptoplasty and in whom hyper-
trophied inferior turbinates were found to be the cause of obstruction.” And he
added: “Atrophic changes of the nasal mucosa or chronic purulent infection
were not observed in any of the patients. Because the results of partial proced-
ures on the inferior turbinates are often unsatisfactory, I suggest performing total
inferior turbinectomy in patients with obstructing inferior turbinates following
rhinoplasty.”101 (Bold italics added)

Apparently cognizant and sensitive to the reality that secondary atrophic rhinitis
may require years to develop, Dr. Ophir and colleagues published (1992) a 10e15-
year follow-up paper and quoted:
 1. Historical perspective 81

“The long-term effectiveness and safety of inferior turbinectomy were assessed

in 186 patients who were interviewed and examined 10 to 15 years after surgery
(mean 12.3 years). Relief of nasal obstruction was reported by 82% of the pa-
tients; rhinoscopy showed wide, clean nasal airways in 88%. The authors
continued: ‘Atrophic changes of the nasal mucosa and chronic purulent infec-
tion were not observed in any of the patients’.”102 (Bold italics added)
Talmon and colleagues,105 published a paper in 2000, a portion which read:
“Over a 6-year period, 357 total inferior bilateral turbinectomies were per-
formed at our institution. We present the results of these procedures and describe
our surgical technique. We conclude that even in a hot and dusty climate, total
inferior turbinectomy is an effective and relatively safe procedure.” (Bold italics
added)
The authors continued: “Total removal of the inferior turbinate is an accepted
surgical procedure for the relief of chronic nasal obstruction. Surgeons hesitated
to use it for two main reasons: (1) total turbinectomy is not “physiologic”; (2) the
procedure is not “safe.” As for the interference of the operation with the physiology
of the nose, this might be true for healthy people. We, instead, operate on patients
with nasal obstruction who are unable to use their noses for breathing. The term
“physiologic” in this connection is inappropriate, and the term “pathological” should
be considered. The results show clearly that the vast majority of patients who un-
dergo this operation do enjoy its outcome and are better off after the operation.”
They continued:
“Ozena (atrophic rhinitis) is believed by some to be related to total inferior tur-
binectomy. This is a serious disease that may discourage surgeons from perform-
ing the operation. In our series, conducted in a hot, dusty climate, no such
complication was observed, nor did we find any documented case in the literature.
We therefore cannot regard ozena as a possible complication of this operation.”
They concluded: “We conclude that total inferior turbinectomy is an effective and
relatively safe procedure, and using the described technique makes it even
safer.“105 (Bold italics added)
We emphasize the importance of agreed upon definition of the terms because
ozena is an example of primary atrophic rhinitis, and we are discussing secondary
atrophic rhinitis. By what standards of evidence-based medicine is total inferior tur-
binectomies an accepted and “relatively safe” surgical procedure as Talmon and col-
leagues claim?
What do they mean by relatively safe and total inferior turbinectomy is an
accepted procedure, by whom? Have any of these practitioners performed a random-
ized control trial (RCT) to remove the possibility of bias and placebo effects?
In Letters to the Editor, Dr. Olawale Olarinde, FRCS(Oto) Department of Otorhi-
nolaryngology Head and Neck Surgery Singleton Hospital Sketty, Swansea SA2
8QA, Wales, was critical of Talmon and colleagues as follows:
“It would have been more appropriate to analyze their results in patients who had
turbinate surgery alone, as this was the procedure being studied. While it is clear
82 CHAPTER 5 The turbinates—an overview

that the authors selected their patients for this procedure, it is unclear what the
selection criteria were. They only state that all patients suffered from chronic
nasal obstruction and failed to respond to local and systemic treatment. This
diagnosis is unfortunately vague.”104
So, Dr. Talmon responded to Dr. Olawale Olarinde in Letters to the Editor as
follows:
“The article is about total inferior turbinectomy. The usual patient has more than
one cause for his or her complaints and usually requires a combined procedure.
Therefore, it is more appropriate to analyze reality rather than a theoretical
model. Second, no operation has a 100% success rate, and inferior turbinectomy
is no exception. Patients should be warned. Unsuccessful intervention is usually
due to reasons other than the excised inferior turbinates: inferior turbinates do
not regenerate after total trimming. I see patients who underwent total turbinec-
tomy 20 years ago and still enjoy the results of the operation. A failure of the pro-
cedure might be due to reasons such as an abundant soft palate or lack of a nasal
valve. Recurrent symptoms are due to conditions such as nasal polyps or hyper-
trophy of the medial turbinates.” Yoav Talmon, MD Dept of Otolaryngology Head
and Neck Surgery Western Galilee Hospital, Nahariya, Israel.105
Also commenting on the paper of Talmon et al. in Letters to the Editor, Ron Eli-
ashar, MD Department of Otolaryngology Head and Neck Surgery Hadassah Uni-
versity Hospital, Jerusalem, Israel, stated:
“I read the paper by Talmon et al. (Talmon Y, Samel A, Gilbey P. Total inferior
turbinectomy: operative results and technique. Ann Otol Rhinol Laryngol
2000; 109:1117e9) with great interest. We ourselves perform total (or subtotal)
inferior turbinectomies routinely in our department. Whenever we discuss this
procedure with our American colleagues, they condemn it because of the risks
of ozena or " empty nose syndrome." It seems that they often regard us almost
as "criminals" when we mention inferior turbinectomy! The most serious compli-
cation encountered by us was massive epistaxis requiring anterior and posterior
nasal packing. There were only a few cases of atrophic rhinitis, and no cases of
ozena or of empty nose syndrome. Some patients developed crusting, but it was
mostly temporary and was relieved by nasal irrigation and application of lubri-
cating gel. The results of our very large series are therefore in line with the results
published by Talmon et al. Hence, I join in their conclusion that total inferior
turbinectomy is effective and relatively safe, at least in our Israeli climate.”
(Bold italics added)
Ron Eliashar, MD Department of Otolaryngology Head and Neck Surgery
Hadassah University Hospital, Jerusalem, Israel.106
So, Dr. Eliashar joins Talmon et al. by promulgating that “total inferior turbinec-
tomy is effective and relatively safe,” nevertheless Dr. Eliashar observed and re-
ported that: “There were only a few cases of atrophic rhinitis, and no cases of
ozena or of empty nose syndrome.” (Bold italics added)
 1. Historical perspective 83

We wonder if it is possible for Talmon et al. or Eliashar to find their previously

operated patients and publish their present-day findings on these patients and
concurrently consider enrolling and performing an important RCT on a new cohort
of patients to remove the possibility of bias and placebo effects?
In a paper from East Africa, Oburra found atrophic rhinitis after bilateral inferior
turbinectomy in 15% of patients, disputing assertions to the contrary.
“Thirty-four patients undergoing bilateral inferior turbinectomy for obstruction
of the upper airway are prospectively reviewed. The indication for the operation
was persistent nasal obstruction interfering with sleep and speech. Their ages
ranged from seven years to 50 years. The most common postoperative complica-
tions were synechiae (15%), atrophic rhinitis (15%), persistent obstruction
(12%), and abnormal nasal sensation (9%).”110 (Bold italics added)
We, the authors of this book, note: that the average annual relative humidity in
Nairobi, Kenya, is 69.0% where the average annual relative humidity in Tel Aviv,
Israel is 70.5%. The fact that Dr. HO Oburra reported a 15% incidence of atrophic
rhinitis (in 5 patients) after bilateral inferior turbinectomy clangs and clashes with
the claim by Dr. Dov Ophir that the relative humidity in Israel prevent the patients
from experiencing atrophic rhinitis after bilateral inferior turbinectomy. (Bold italics
added).

Table 5.2 Pattern of complications.

No. of
Complication patients %

Synechiae 5 15
Atrophic rhinitis 5 15
Persistent obstruction 4 12
Abnormal sensation in 3 9
the nose
Severe epistaxis 2 6
Rhinnorrhoea 2 6
Infection 1 3
Numbness of the left 1 3
incisors

Table 5.2 “Pattern of complications” following bilateral turbinectomy in the pa-

per by Oburra.110 Note the incidence of atrophic rhinitis 15% and “severe”
epistaxis 6%. (Bold italics added)
84 CHAPTER 5 The turbinates—an overview

Others declared that patients who received partial or even full total turbinectomy
experienced no “untoward sequelae.” So, a debate, which flourished for more than a
century was sustained and nourished by colleagues in Europe, the Middle East, and
in our country was again in full bloom even after ample numbers of previous sur-
geons cautioned the profession that the nasal mucosa is “the organ of the nose”
and that total resection can result in disaster, as we also have observed on hundreds
of occasions.18 In our country, other highly experienced and respected surgeons
wrote:
“Full-thickness excision of the anterior third to half of the inferior turbinate (tur-
binectomy) became a favored procedure. Relief of nasal obstruction was obtained
in greater than 90% of patients. Healing was satisfactory regardless of the
method, and complications, including hemorrhage and infection, were few.
Long-term follow-up revealed no untoward sequelae, and no patient developed
atrophic rhinitis.”87 (Bold italics added)
Wondering and questioning, what happened to the other 10% of their patients?
In 1983, while at the University of Nebraska, Martinez et al. published in The
Laryngoscope:
“Total inferior turbinectomies have been performed on 40 patients over the past
5 years; 29 of these patients have been followed from 2 to 60 months postopera-
tively by clinical examination and by formal questionnaire.” The authors
continue: “The inferior turbinates play a role in humidification and temperature
regulation of inspired air. The removal of them, however, does not seem to be
fraught with the morbidity which has heretofore been attributed to this proced-
ure.”103 (Bold italics added)
George Drumheller, MD of Everett, Washington, wrote a letter to the editor of
The Laryngoscope regarding the Martinez et al. paper: Martinez SA, Nissen AJ,
Stock CR, Tesmer T. Nasal turbinate resection for relief of nasal obstruction. Laryn-
goscope 1983 Jul; 93 (7):871e5.
“The teachers of the American Rhinologic Society are frequently being asked by
students and others regarding our treatment of malfunctions and pathologic sit-
uations which are manifested in the nasal turbinates. It is most incredible that
the article shows a picture of ‘normal regenerated respiratory epithelium with
mucous and serous glands.’ In order to be normal, the nasal cycle must be present,
and certainly this is not the case after turbinectomy. In addition, many other naso-
pulmonary reflexes are disturbed, and certainly pre- and postoperative case
studies should be included in any article addressing this subject. It is regrettable
that many of our young surgeons will take the easy route of resecting a turbinate
which nobody can reconstruct, and the morbidity rate will be markedly increased
as a result of this very poorly worked up article.”
In the same edition of The Laryngoscope, Pat Barelli, MD, a rhinologist from
Kansas City, Missouri, said:
 1. Historical perspective 85

“I have in my practice many people who have had turbinectomies with disastrous
results. The treatment of these postoperative turbinectomies is extremely unsatis-
factory as one cannot reconstruct a turbinate which is not present.”
*Editorial Note (from The Laryngoscope): “This paper (Martinez et al.)103 is a South-
ern Section meeting paper. Triological Society papers are not usually reviewed. They
are accepted. For the most part, for publication when the author is accepted as a
speaker for a Triological meeting. Publication does not necessarily mean approval,
but rather indicates what is going on in the profession.”
Moore et al. also at the University of Nebraska followed the identical patients
initially reported by Martinez et al. With the additional follow-up of several years,
Moore and colleagues emphatically contradicted the initial findings by Martinez
et al.103 concluding that:
“Total inferior turbinectomy has been proposed as a treatment for chronic nasal
airway obstruction refractory to other, more conservative, methods of treatment.
Traditionally, it has been criticized because of its adverse effects on nasophysiol-
ogy. In this study, patients who had previously undergone total inferior turbinec-
tomy were evaluated with the use of an extensive questionnaire. It confirms that
total inferior turbinectomy carries significant morbidity and should be con-
demned.”2 (Bold italics added)
Segal and colleagues from Tel Aviv University Israel operated on 227 children
under the age of 10 followed one year after surgery and to our dismay and disap-
pointment concluded:
“Conclusions: A complete inferior turbinectomy should be considered in
children <10 years of age who have hypertrophied inferior turbinates that cause
major interference with nasal breathing.”113 (Bold italics added)
At this moment, we ask Dr. Segal or one of his colleagues (Eviatar, Berenholz,
Kessler, or Shlamkovitch), can you please present to the profession, an update
regarding the “long-term results” of your 227 children after your “complete inferior
turbinectomy” published 18 years ago in your paper of 2003?113
Admittedly, we are not reluctant reticent envoys but ferocious opponents of the
brazen ideology of total inferior turbinectomy along with others2e4,18e28 including,
arguably the greatest, 20th century American rhinologist and pedagogue Maurice H.
Cottle, MD of Chicago, who once told me, and to the best of my recollection, and
most assuredly the word “criminal” remains in mind:
“.aggressive resection of the inferior turbinate for nonmalignant disease can be
considered a criminal act.” Personal communication (EBK).
In present-day state-of-the-art of nasal surgery, it would be vastly valuable to un-
derstand how much nasal mucosal tissue, with its critical breathing (respiratory) and
defensive functions can be safely removed, damaged or impaired, without producing
nasal functional failure resulting in empty nose syndrome (ENS). How often does
86 CHAPTER 5 The turbinates—an overview

the contemporary nasal surgeon consider the conjectural functional residual capacity
of the nose (FRCn) before or after surgical intervention, especially with total inferior
turbinectomy in mind?
Another confounding reality is that in the current state of nasal functional testing,
it appears an estimate of nasal function is often based on observation or the patient’s
subjective assessment, using a visual analog scale. Several other pertinent quotations
from Lord Kelvin’s scientific perspicacious pen include:
“To measure is to know.” “If you cannot measure it, you cannot improve it.”*
*PLA, Volume 1, “Electrical Units of Measurement”, 1883-05-03 PLA- Popular Lec-
tures and Addresses (1891e1894, 3 volumes)
Concluding this overworked and well-worn section of the historical perspective
of the turbinate debate, the work of Jackson and Koch from the Division of Otolar-
yngology Head and Neck Surgery, Stanford University Medical Center published in
the journal Plastic and Reconstructive Surgery in 1999 summarized the advantages
and disadvantages of inferior turbinate treatment as follows:
“After correcting septal and nasal valve pathology persistent nasal airway
obstruction may be the result inferior turbinate enlargement (hypertrophy) for
which a graduated “staged” approach is recommended all the while minimizing
hemorrhage and postoperative atrophy (nasal drying).”119

1. Injections: Intraturbinate steroid injections although minimally invasive

improvement is not long-lasting and the potential for blindness exists, but it is
not as common as was once thought.120e122
2. Out-fracture (lateralization): Minimally invasive with a low risk of compli-
cations; however, turbinate mucosal pathology is not addressed.
3. Non-surgical Turbinate Reduction Adjunctive Procedure (n-s TRAP):
(a) Electrocautery. routine and not technically difficult; delayed hemorrhage
may occur.
(b) Cryosurgery. routine and not technically difficult; brief relief of symptoms.
(c) Laser surgery . routine and not technically difficult; brief relief of symp-
toms, postoperative crusting unable to change the bony (concha).
4. Surgical procedures:
(a) Partial turbinectomy. routine and not technically difficult; severe hemor-
rhage can occur, nasal airway relief can last for years; however, synechia,
prolong crusting, and ENS can develop.
(b) Total turbinectomy. routine and not technically difficult; severe hemor-
rhage can occur, nasal airway relief can last for years; however, synechia,
protracted crusting, and ENS may develop along with a disturbance in
physiological function, resection is irrevocable.
(c) Turbinoplasty. pseudostratified ciliated respiratory epithelium is pre-
served, reduction of cases of hemorrhage, high incidence of relief of nasal
 2. Turbinate anatomy 87

airway obstruction, incidence of nasal atrophy, and ENS is exceedingly low

and can be combined with out-fracture (lateralization).
There are three options for turbinoplasty while still maintaining preservation of
the pseudostratified ciliated respiratory epithelium.
1. Submucosal (parenchymal) resection alone, WITHOUT conchal bone resection
2. Conchal bone resection alone, WITHOUT submucosal (parenchymal) resection
3. Combined submucosal (parenchymal) resection combined WITH conchal bone
resection
Jackson and Koch concluded that nasal airway obstruction secondary to turbinate
hypertrophy must first receive medical therapy before contemplating any surgical
intervention. They clearly recognized that surgical treatment should be conservative,
with minimal morbidity. As a consequence of that reality, they favored “increasingly
invasive interventions” after a failure of medical management, first with laser appli-
cation as an initial office procedure followed by partial inferior turbinectomy or sub-
mucosal resection, “and rarely total turbinectomy or vidian neurectomy” if other
treatments are unsuccessful. They unambiguously acknowledged that definitive
guidelines for rational therapeutic decisions regarding the inferior turbinate were
lacking; therefore, they favored continued studies as a necessary requirement for
sensible therapeutic choices.119

2. Turbinate anatomy
Customarily, the general term turbinate is understood to mean the nasal structure
composed of an overlying pseudostratified ciliated respiratory epithelium with a
subepithelial layer (synonyms include submucosa, lamina propria, stroma); this sub-
mucosa (lamina propria, stroma) is composed of neurovascular bundles, especially
large capacitance vessels. This submucosa (lamina propria, stroma) together with
the conchal bone and the overlying epithelium form the entire turbinate. Anatomi-
cally, the turbinates are often divided into the anterior portion (head), a midportion
(body), and posterior portion (tail), which has utility allowing thinking about which
portion of a turbinate to modify.

2.1 Anatomy of the middle turbinate

The middle turbinate is part of the ethmoid bone; superiorly, it connects to the crib-
riform region receiving its blood supply posteriorly by the sphenopalatine artery and
anteriorly from the anterior ethmoid artery, a branch off the ophthalmic artery sup-
plied by the internal carotid arterial system. The osseous skeleton can be structured
as lamellar or bullous bone (concha bullosa). The concha bullosa is lined with pseu-
dostratified ciliated respiratory epithelium, which drains into the ethmoid infundib-
ulum, which on occasion may expand significantly to obstruct the nasal airway.
88 CHAPTER 5 The turbinates—an overview

As pointed out by Scheithaurer,28 there are numerous middle turbinate anatomic

variations which may be classified as follows:
1. Bulbous form (concha bullosa) with pneumatization in the horizontal plane
2. Lamellar form with pneumatization in the vertical plane
3. Combined bulbous and lamellar forms
4. Paradoxical curve
5. Extra concha
The most common form of middle turbinate anatomic variant is the concha bul-
losa, while the most common pathologic form is the polypoid change, which is
commonly associated with chronic rhinosinusitis. Since the mucosa of the middle
turbinate is highly vascularized, it plays an important role in humidification of the
inspired air.

2.2 Anatomy of the inferior turbinate

The inferior turbinate is the largest of the turbinates and slightly larger in males than
in females being approximately 4.9 cm in men and 4.7 cm in women. The outer
mucosal layer is pseudostratified ciliated respiratory epithelium, while the subepi-
thelial layer (submucosa, lamina propria, stroma) contains an extensive network
of venous capacitance vessels (sinusoids). Figs. 5.1e5.3.

FIGURE 5.1
An intranasal mucosal biopsy of a patient with the “Empty Nose Syndrome.” The normal
ciliated columnar respiratory epithelium is frequently replaced by squamous metaplasia
seen in these patients with the “Empty Nose Syndrome.”
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
 2. Turbinate anatomy 89

FIGURE 5.2
The normal nasal mucus membrane is composed of an outer epithelial layer with four
different cell types and a deeper submucosal layer. The outer epithelial layer contains the
ciliated columnar cells (approximately 100 to 250 cilia/cell with microvilli) and nonciliated
columnar cells (with microvilli, increasing their functional surface area), mucus-secreting
goblet cells and basal cells, which are diminutive in size and rest upon a basement
membrane. Submucosa (lamina propria, stroma). The submucosa contains
neurovascular fenestrated capillaries, mixed glandular elements, and an extensive zone
of venous cavernous plexuses.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

It is the subepithelial layer that is involved in the “nasal cycle,” defined as the
alternating episodic congestion and decongestion of the nasal turbinates.
Figs. 5.4e5.7. The physiologic reality of the “nasal cycle” has to be taken into
consideration when examining the patient; therefore, the internal nose requires ex-
amination before and after decongestion.123,124
This fluctuation induced by the submucosal venous sinuses results in a variation
of nasal airflow from one nasal chamber to the other side, which occurs over several
hours throughout the day. This cycle occurs in approximately 80% of healthy
adults.125,126 Flanagan and Eccles observed the nasal cycle in 20%e40% of
(n ¼ 52) healthy volunteer adults. They went on to say:
“The cycle is adrenergic-stimulated. It is suspected that the activity of the sympa-
thetic nerve is subject to changes which are regulated via the respiratory center in
the brain stem and which are closely associated with breathing activity.”12,127
According to Williams and Eccles, the nasal cycle slows with age and the recip-
rocal changes in nasal airflow may be organized and controlled from the
90 CHAPTER 5 The turbinates—an overview

FIGURE 5.3
Electron microscopic view of nasal respiratory cilia. The central strand of a cilium is
composed of two single centrally located microtubules surrounded by an array of nine
pairs of peripheral microtubules with both inner and outer dynein arms. The dynein arms
are absent in patients suffering from primary ciliary dyskinesia.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

hypothalamus and brainstem.128,129 The answer to the question, what is the function
of the nasal cycle was proposed by Eccles who stated:
“It is proposed that the periodic congestion and decongestion of nasal venous si-
nusoids may provide a pump mechanism for the generation of plasma exudate, and
that this mechanism is an important component of respiratory defence.”130,131
These venous capacitance vessels (sinusoids) in the submucosa (lamina propria,
stroma) exist in the middle turbinate but are more numerous in the inferior turbinate.
These vessels can dilate to the point of totally obstructing the nasal airway. The
blood supply is controlled by sympathetic innervation to the arterial resistance ves-
sels. The mucous membrane is decongested when both the venous capacitance ves-
sels (sinusoids) and the resistance vessels receive sympathetic stimulation as both
are surrounded by adrenergic nerve fibers.132,133
Fundamentally, the nasal autonomic nervous system maintains the ability to con-
trol systems:
System 1 controls nasal secretion with parasympathetic innervation, and system
2 controls nasal airflow with sympathetic innervation.
In addition to controlling nasal secretions, the parasympathetic system influences
the vascular system by the neurotransmitter acetylcholine and the potent vasodilator,
vasoactive intestinal polypeptide. The sympathetic nerves are distributed to both the
 2. Turbinate anatomy 91

FIGURE 5.4
The Nasal Cycle is described as the normal physiologic alternating congestion and
decongestion of the nasal turbinates. This alternating congestion decongestion cycle
produces rotating changes of the nasal resistance on each side (uninasal resistance
alterations) of the nasal airway. As a consequence of this nasal cycling, the side congested
(obstructed) rotates or “cycles” to become decongested (unobstructed), while the
opposite side becomes congested (obstructed). This nasal cycling occurs between 20%
and 80% of the adult population.126e130 On this CT scan above, source Wikipedia, https://
en.wikipedia.org/wiki/Nasal cycle, at that specific time, the left inferior turbinate is
congested while the right inferior turbinate is decongested by comparison.

blood vessels and nasal glands.134 The venous capacitance vessels (sinusoids) in the
submucosa have a dense adrenergic sympathetic innervation, and sympathetic
nerve stimulation produces vasoconstriction with a mucosal blood volume reduc-
tion.135,136 Noradrenaline is the primary sympathetic neurotransmitter along with
neuropeptide Y, both are vigorous vasoconstrictors.137
The role of the nasal venous sinuses in the control of nasal airflow is now well recog-
nized, and their ability to swell and completely obstruct the nasal passage has been
observed and reported.5,131,134 The location of the nasal venous sinuses at the anterior
tip of the inferior turbinate and nasal septum is critical for controlling nasal airflow,
and this area of the nose is often referred to as the “nasal valve.” The nasal valve
area is the narrowest point of the nasal passage, which determines the nasal resistance
to airflow.5,25,138,139 However, there is some dispute in the literature as to whether the
nasal valve lies in the nasal vestibule or more posteriorly within the bony cavum of the
nose. The anatomical and physiological evidence indicates that the nasal valve occurs
at the entrance of the piriform aperture, with the major site of nasal resistance just
anterior to the tip of the inferior turbinate.140,141
The inferior turbinate is inserted into the lateral wall of the nose at approximately
the mid-maxillary wall location. This insertion is located at varying angles, ranging
from approximately 20 to 90 from the mid-maxillary wall. This anatomic fact has
surgical implications when performing out-fracture (lateralization) of the inferior
92 CHAPTER 5 The turbinates—an overview

FIGURE 5.5
Composite graph demonstrating the presence of a nasal cycle, which occurs in 20% to
80% of the adult population. The values were obtained over a five-hour study period using
active anterior rhinomanometric techniques. Using rhinomanometry, transnasal pressure
and transnasal airflow during active breathing (inspiration and expiration) can be
measured when breathing only through the right side, breathing only through the left side,
and when breathing through both sides (both nostrils) at the same time. The Nasal Cycle
is described as the normal physiologic alternating congestion and decongestion of the
nasal turbinates. This alternating congestion decongestion cycle produces alternating
changes of the nasal resistance on each side (uninasal resistance alterations). After the
passage of time, the opposite side “cycles” becomes congested (obstructed), while the
opposite side becomes decongested. Nasal resistance in Pa/cm3/s is measured at 150 Pa
(Pascals) pressure. The nasal resistance can be calculated by measuring transnasal
pressure divided by transnasal nasal air flow. The nasal resistance for either right or left
side is an “uninasal” resistance that can be calculated from the pressure and flow
measurements. The total nasal resistance is calculated from the transnasal pressure
divided by the transnasal airflow when breathing through both nostrils at the same time.
When breathing through both sides, the patient feels unobstructed as the total nasal
resistance is lower (less) than either one of the individual’s right-sided resistance or left-
sided resistance of the nose as depicted in the graph of the nasal cycle above. Most
people are simply unaware of the presence of the alternating congestion decongestion
phases of the nasal cycle.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

turbinate as the optimal point of out-fracture (lateralization) should be as close to the

actual insertion to the lateral wall as possible, thereby producing a comminuted frac-
ture of the conchal bone, allowing repositioning of the inferior turbinate in a more
lateral position, thereby opening (widening) the internal nasal valve area.
 3. Physical examination 93

FIGURE 5.6
With this schematic drawing of active anterior mask rhinomanometry, as used at the Mayo
laboratory, the investigator is able to objectively measure the pressure difference between
the nostril and the nasopharynx while simultaneously measuring the airflow through the
side under study. Each nasal cavity, right and left side, is measured separately. The
measurements of transnasal airflow and pressure changes during breathing (inspiration
and expiration) can be reordered and visualized. From these measurements, nasal
resistance can be calculated using the formula: Nasal resistance equals transnasal
pressure divided by transnasal air flow.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

3. Physical examination
Recollect that effective medical management of turbinate enlargement involves ac-
curate diagnosis and eliminating medical iatrogenic causes of turbinate swelling.
Infection (by viral, bacterial, rickettsia, fungal, or other infectious agents), allergic
rhinitis, nonallergic rhinitis (NARES syndrome), pregnancy, hypothyroidism, and
medications such as beta-blockers, antihypertensives, antidepressants, some certain
oral contraceptives can induce nasal mucosal engorgement. Abuse of topical decon-
gestants may result in “rhinitis medicamentosa” that can be reversed with medica-
tion. Environmental irritants such as cigarette smoke can be responsible and
eliminated by smoking cessation and/or air filtration. Turbinate swelling is regularly
caused by venous congestion, capable of producing both the nasal cycle and a well-
known gravitational and physiological response, especially when a person assumes a
lateral or supine position. These gravitational and physiological responses can be
mitigated with positional changes and elevation of the head with pillows or elevating
the head of a bed with blocks. The examining physician needs to be mindful of the
assorted sources of turbinate enlargement so that accurate diagnosis is reached.
94 CHAPTER 5 The turbinates—an overview

FIGURE 5.7
With active anterior mask rhinomanometry, as used in our clinical laboratory at Mayo, the
individual is studied while seated during quiet breathing. The pressure changes between
the nostril opening and the posterior nasopharynx are measured through an airtight fitted
tube, on the one side, measuring the transnasal pressure changes on the opposite side, in
this example, the left side. A pneumotachograph is connected to the mask which
measures the nasal airflow on the tested side, in this example, the left side. From these
reordered and visualized measurements of transnasal pressure and transnasal airflow
during breathing (inspiration and expiration), nasal resistance can be calculated and the
existence of a nasal cycle confirmed.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

Preoperative evaluation includes complete medical, surgical history, and phys-

ical examination including anterior rhinoscopy of the internal nasal structures
including the internal and external nasal valves, the septum, all mucosal surfaces,
including evaluation of the turbinates, the cribriform region, and choana before
and after topical sympathomimetic decongestion (and 4% xylocaine when instru-
mentation, palpation, or biopsy is indicated). Subsequent to anterior rhinoscopy,
endoscopic (rigid and flexible telescopes) examination is performed studying all
nasal structures including the nasopharynx to evaluate the nasopharyngeal space
and the posterior portion (tails) of the turbinates.
Farmer and Eccles found no evidence for cellular hypertrophy despite the com-
mon use of the term “turbinate hypertrophy” arguing that the term “turbinate hyper-
trophy” should be replaced with a more correct term, “turbinate enlargement.”142
The precise definition of hypertrophy is an increase in cell size while hyper-
plasia is an increase in cell number. Farmer and Eccles found that turbinate
enlargement is largely the result of, “cellular hyperplasia, tissue edema, and vascular
congestion” and not the result of an increase in cell size. Continuing with defini-
tions, metaplasia is the conversion of one type of cell to another, for example,
cellular change from pseudostratified ciliated columnar epithelial cells to squamous
 4. Rhinologic evaluation with assessment tests and biopsy 95

cells, squamous metaplasia. Fig. 5.1. Any normal cell may become a cancer cell by
changing to an abnormal cell first by hyperplasia (increase in the number of cells)
and then dysplasia (increase in the number of abnormal cells).

4. Rhinologic evaluation with assessment tests and biopsy

The diagnostic assessment tests are summarized in Table 5.3.

Table 5.3 Assessment tests and biopsy.

1. Saccharine test of mucociliary transport143,144

2. Schirmer test145,146
3. Olfaction testing147,148
4. Acoustic rhinometry (AR)149
5. Rhinomanometry (RM)150,151
Note: Rhinomanometry is generally accepted as the standard technique of measuring
nasal airway resistance and assessing the patency of the nose.
6. Peak nasal inspiratory flow (PNIF)152,153
Note: The peak nasal inspiratory flow (PNIF), acoustic rhinometry (AR), and
rhinomanometry (RM) assess different aspects of nasal obstruction. These methods
“generally” relate to each other and can be alternatively applied to research and
clinical practice (Bold italics added).
7. Computational fluid dynamics (CFD)154
8. Nasal secretions155,156
a. Secretory IgG, IgA, IgM, IgE, IgD
b. CSF fluid
9. Nasal smear cytology157
a. Lymphocytes
b. Eosinophils
Note: “A significant correlation was obtained between secretion eosinophilia and
allergy. Nasal provocation tests correlated with skin tests in 87%, whereas the
correlation between nasal provocation tests and IgE determinations in the serum was
poorer.” 157
10. Allergy testing
a. Skin prick testing
b. Blood immunoassay testing
Note: Enzyme-linked immunosorbent assay (ELISA or EIA) is obtained for allergen-
specific antibodies
c. Elimination diet
d. Provocation testing
11. Imaging studies
12. Nasal biopsy
a. Light microscopy
b. Electron microscopy
96 CHAPTER 5 The turbinates—an overview

Results from these tests are combined with clinical findings to reach a reasoned
conclusion in the decision-making process. Therefore, it is the blending and corre-
lation of the patient’s symptoms, findings of the diagnostic studies integrated with
the pathology found on physical nasal examination that allows accurate diagnosis.
Currently, because of the immense improvements made in measurement technology,
the objective assessment of the minimal cross-sectional area (acoustic rhinome-
try)149 along with the investigation of the transnasal airflow and transnasal pressure
changes (rhinomanometry)150 have now attained a very high standard. Nevertheless,
the data collected do not always correspond to the subjective experience of the pa-
tient. Cole has previously acknowledged this drawback as early as 1989 with the
finding that approximately 20% of patients experiencing nasal airway obstruction
when measured rhinomanometrically had either a normal or reduced nasal resistance
when compared to controls (general population).158,159 Nonetheless, in the context
of the preoperative assessment, these two procedures, acoustic rhinometry and rhi-
nomanometry have been established, by the leader of the University of Toronto
group, Professor Philip Cole, MD, as important tools in the routine diagnostic
assessment of the rhinologic patient with nasal airway obstruction.158,159
 CHAPTER

Brief history of
evidence-based medicine
—David Sackett, MD 6
According to Thoma and Eaves, The British Medical Journal conducted an online
poll of its readers in January 2007 finding that evidence-based medicine (EBM)
was ranked seventh among the 15 most momentous milestones molding modern
medicine. Some of these major milestones included sanitation (germ theory of dis-
ease), immunization (vaccines), antibiotics, and anesthesia along with imaging
(radiology) noting that a Google search today (in 2015) regarding anything to do
with EBM would be in the millions.160
Who was behind the concept of EBM, simply, what is EBM, how did it all come
about, and why is it pertinent to our conversation in this book?
The imaginative original unifying ideas behind EBM comes from David Sackett,
MD considered the “father” of EBM. We reason that EBM is primarily about discov-
ery. Discovery of the “best evidence,” optimistically “proof positive”; using that
proof of the best medical “scientific evidence,” as opposed to the best “expert
opinion,” for crafting clinical choices, judgments, and rational therapeutic decisions
in the best interest of the patient.
In their tribute to Dr. Sackett, authors Thoma and Eaves160 defined EBM
essentially as the combination of:
1. Finding, from the literature, the supreme scientific research evidence coupled
2. With a given physician’s clinical expertise
3. Integrated with an understanding of an individual patient’s unique situation,
values, and wishes.
In other words, EBM is defined as the combination of the best research evidence
integrated with a given clinicians expertise and blended with the individual patient’s
needs and values.161e163
Dr. David Sackett, born in Chicago in 1934, obtained his medical degree at the
University of Illinois, trained in internal medicine with a subspecialty in nephrology.
He attended Harvard University earning a Master’s degree in epidemiology prac-
ticing clinical medicine in Chicago, Buffalo, and Boston in the United States. At
age 33 (1967), he left the United States and founded the first Department of Clinical
Epidemiology at McMaster University Medical School in Hamilton, Ontario, Can-
ada, which was the first department of epidemiology in the world.160
EBM effectively began when a group of McMaster University epidemiologists,
guided by Dr. Sackett, published their 1979 article in The Canadian Medical

Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00006-8 97

Copyright © 2024 Elsevier Inc. All rights reserved.
98 CHAPTER 6 Brief history of evidence-based medicine—David Sackett, MD

Association Journal counseling physicians as to how to evaluate the medical litera-

ture. The precise term “evidence-based medicine” was actually conceived and pub-
licized by internist Dr. Gordon Guyatt, who was one of Dr. Sackett’s
students.160,163e165
The bedrock of EBM is the tiered system of organizing evidence known as levels
of evidence (LOEs). The concept of “LOEs” was initially presented and explained in
the report by the Canadian Task Force on the Periodic Health Examination in
1979.165 The Task Force’s purpose was to provide recommendations for the periodic
health examination based on evidence obtained from the medical literature. The au-
thors established a system of rating the evidence from the published literature deter-
mining the value of that particular evidence. For example, a high-level value was
assigned to exceptional evidence supporting a recommendation for a specific med-
ical condition which was to be included in the health examination.
In a 2011 paper by Burns et al., a clear summary of the history of LOEs was suc-
cinctly presented and described in tables below (Tables 6.1 and 6.2).166
Both systems place randomized controlled trials (RCTs) at the highest level and
case series or expert opinions at the lowest level. The hierarchies rank studies ac-
cording to the probability of bias. RCTs are given the highest level because they
are designed to be unbiased having less risk of systematic errors.
A case series or expert opinion is often biased by the author’s experience or opin-
ions, without controlling for confounding factors. In order to answer any clinical
question, the highest LOE should always be applied. In other words, a major goal
of EBM practice is finding the highest LOE to solve a clinical problem. It is impor-
tant to understand the history behind the levels and how they should be interpreted
since not all level I evidence even from an RCT is perfect.169 Since the introduction
of LOEs, numerous organizations and journals have adopted variations of the clas-
sification system. Diverse specialties are often asking different questions, and it was

Table 6.1 Canadian task force on the periodic health examination’s levels of
evidencea.
Level Type of evidence

I At least one RCT* with proper randomization

II.1 Well-designed cohort or case-control study
II.2 Time series comparisons or dramatic results from uncontrolled studies
III Expert opinions
*RCT, randomized controlled trial.
a
Adapted from Canadian Task Force on the Periodic Health Examination. The periodic health exam-
ination. Can Med Assoc J 1979;121:1193e1254.165
Table 6.1 amended from Burns et al.166
 Brief history of evidence-based medicinedDavid Sackett, MD 99

Table 6.2 Levels of evidence from Sacketta.

Level Type of evidence

I Large RCTs* with clear-cut results

II Small RCTs with unclear results
III Cohort and case-control studies
IV Historical cohort or case-control studies
V Case series, studies with no controls
*RCTs, randomized controlled trials.
a
Adapted from Sackett DL. Rules of evidence and clinical recommendations on the use of antith-
rombotic agents. Chest. 1989;95:2Se4S.169
Table 6.2 amended from Burns et al.166

recognized that the type of evidence and LOE needed modification accordingly.
Research questions are divided into the following four categories:
1. Treatment (Therapeutic)
2. Prognosis
3. Diagnosis
4. Economic/decision analysis.
For example, Table 6.3 shows the LOEs developed by the American Society of
Plastic Surgeons for prognosis167, and Table 6.4 shows the levels developed by the
Centre for Evidence-Based Medicine for treatment (therapeutic studies).168 These
two tables feature the types of studies that are appropriate for the question of prog-
nosis versus questions of treatment. This very important distinction is made because
RCTs are not appropriate when looking at the prognosis of a disease.

Table 6.3 Levels of evidence for prognostic studiesa.

Level Type of evidence

I High-quality prospective cohort study with adequate power or systematic review

of these studies
II Lesser quality prospective cohort, retrospective cohort study, untreated controls
from an RCT*, or systematic review of these studies
III Case-control study or systematic review of these studies
IV Case series
V Expert opinion; case report or clinical example; or evidence based on physiology,
bench research, or “first principles”
*RCT, randomized controlled trial.
a
Adapted from the American Society of Plastic Surgeons. Available at: http://www.plasticsurgery.org/
For_Medical-Professionals/Legislation-and-Advocacy/Health-Policy-Resources/Evidence-based-
GuidelinesPracticeParameters/Description-and-Development-of-Evidence-based Practice-
Guidelines/ASPS-Evidence-Rating-Scales.html. Accessed December 17, 2010.167
Table 6.3 amended from Burns et al. for questions of prognosis.166
100 CHAPTER 6 Brief history of evidence-based medicine—David Sackett, MD

Table 6.4 Levels of evidence for therapeutic studiesa.

Level Type of evidence

1a Systematic review (with homogeneity) of RCTs*

1b Individual RCT (with narrow confidence intervals)
1c All-or-none study
2a Systematic review (with homogeneity) of cohort studies
2b Individual cohort study, including low-quality RCTs; (e.g., <80% follow-up)
2c “Outcomes” research; ecological studies
3a Systematic review (with homogeneity) of case-control studies
3b Individual case-control study
4 Case series (and poor-quality cohort and case-control study)
5 Expert opinion without explicit critical appraisal or based on physiology, bench
research, or “first principles”
*RCTs, randomized controlled trials.
a
From the Centre for Evidence-Based Medicine (Web site). Available at: http://www.ccbm.net.
Accessed December 17, 2010.168
Table 6.4 amended from Burns et al. for questions of treatment.166

A prognosis does not compare treatments; therefore, the highest LOE comes
from a cohort study and not from an RCT for questions of prognosis. Obviously,
the physician must consider the quality of the data, since a poorly designed RCT
has little merit; consequently, it may be at the same LOE as a cohort study. The ques-
tion in this instance is, “What will happen to the patient if we do nothing at all?”
Because a prognosis question does not involve comparing treatments, the highest ev-
idence would come from a cohort study or a systematic review of cohort studies and
again not from an RCT.
The LOEs must also consider the quality of the data. For example, in Table 6.4
from the Centre for Evidence-Based Medicine, a poorly designed RCT has the same
LOE as a cohort study. A grading system that provides strength of recommendations
based on evidence has also changed over time.
Table 6.5 shows the Grade Practice Recommendations developed by the Amer-
ican Society of Plastic Surgeons. The grading system provides an important compo-
nent in EBM and assists in formulating clinical decisions. For example, a strong
recommendation is given when there is level I evidence in concert with consistent
evidence from level II, III, and IV studies available. The grading system does not
degrade lower-level evidence when deciding recommendations if the results are
consistent. Although RCTs are often assigned the highest LOE, not all RCTs are
conducted properly, and it is our responsibility to scrutinize the results
carefully.167,168
Sackett169 stressed the importance of estimating types of errors and the power of
studies when interpreting results from RCTs. For example, a poorly conducted RCT
may report a negative result because of low power when in fact a real difference ex-
ists between treatment groups. The Jadad scale has been developed to judge the
 Brief history of evidence-based medicinedDavid Sackett, MD 101

Table 6.5 Grade practice recommendations.*

Grade Descriptor Qualifying evidence Implications for practice

A Strong Level I evidence or Clinicians should follow a

recommendation consistent findings from strong recommendation
multiple studies of levels unless a clear and
II, III, or IV compelling rationale for an
alternative approach is
present
B Recommendation Levels II, III, or IV Generally, clinicians should
evidence, and findings follow a recommendation
are generally consistent but should remain alert to
new information and
sensitive to patient
preferences
C Option Levels II, III, or IV Clinicians should be flexible
evidence, but findings are in their decision-making
inconsistent regarding appropriate
practice, although they may
set bounds on alternatives;
patient preference should
have a substantial
influencing role
D Option Level V evidence: little or Clinicians should consider all
no systematic empirical options in their decision-
evidence making and be alert to new
published evidence that
clarifies the balance of
benefit versus harm; patient
preference should have a
substantial influencing role
From the American Society of Plastic Surgeons. Evidence-based clinical practice guidelines. Available
at: http://www.plasticsurgery.org/MedicalProfessionals/HealthPolicyandAdvocacy/HealthPolicyRes
ources/Evidence-basedGuidelinesPracticeParameters/DescriptionandDevelopmentofEvidence-based
PracticeGuidelines/ASPSGradeRecommendationScale.html. Accessed 3 March 2011.

quality of RCTs.170 Remember, do not assume that all level 1 studies are of higher
quality than level 2 studies. Although the goal is to improve the overall LOE in med-
icine and surgery, this does not mean that all lower-level evidence should be dis-
carded. Case series reports are important for hypothesis generation, which leads
to more questions and further controlled studies. In addition, in the face of over-
whelming evidence to support a treatment, such as the use of antibiotics for wound
infections, there is no need for an RCT.
Some basic items that should be considered for assessing RCTs include a
description of the randomization and blinding process, a description of the number
of subjects who withdrew or dropped out of the study, the confidence intervals
around study estimates, and a description of the power analysis. Although RCTs
102 CHAPTER 6 Brief history of evidence-based medicine—David Sackett, MD

may not be appropriate for many surgical questions, well-designed and well-
conducted cohort or case-control studies could boost the LOE.
Clearly, LOEs are an important component of EBM. Understanding the levels
and why they are assigned to publications and abstracts helps the reader to prioritize
information. This is not to say that all level IV evidence should be ignored and all
level I evidence accepted as fact. The LOEs provide a guide, and the reader needs
to be cautious when interpreting these results.166
Many of the current studies in the literature tend to be descriptive and lack a con-
trol group. The way forward seems clear. Surgery researchers need to consider using a
cohort or case-control design whenever an RCT is not possible. If designed properly,
the LOE for observational studies can approach or surpass those from a RCT. In some
instances, observational studies and RCTs have yielded similar results.171 If enough
cohort or case-control studies become available, the prospect of systematic reviews
of these studies will increase, which will increase overall evidence levels in surgery.
So, it is the understanding of the LOE, also titled the hierarchy of evidence, and
how studies are assigned specific levels are purely based on the methodological
quality of their design, validity, and applicability to a specific patient care situation.
These decisions are assigned levels of strength or hierarchies of recommendation.

Table 6.6. Level of evidence.

Level of
evidence (LOE) Description
Level I Evidence from a systematic review or metaanalysis of all relevant
andomized controlled trial (RCTs) or evidence-based clinical
practice guidelines based on systematic reviews of RCTs or three or
more RCTs of good quality that have similar results.
Level II Evidence obtained from at least one well-designed RCT (e.g., large
multisite RCT).
Level III Evidence obtained from well-designed controlled trials without
randomization (i.e., quasiexperimental).
Level IV Evidence from well-designed case-control or cohort studies.
Level V Evidence from systematic reviews of descriptive and qualitative
studies (metasynthesis).
Level VI Evidence from a single descriptive or qualitative study.
Level VII Evidence from the opinion of authorities and/or reports of expert
committees.
Adapted from Ackley BJ, Swan BA, Ladwig G, Tucker S. Evidence-based nursing care guidelines:
medical-surgical interventions. St. Louis, MO: Mosby Elsevier; 2008:7.172

Diverse clinical questions are best answered by different varieties of research

findings. Realize that the answer to your clinical question might not be found at
the highest LOE, that is with a systematic review or metaanalysis. If this occurs,
choose the next highest LOE. This table below suggests study designs best suited
to answer specific clinical questions.172
 Brief history of evidence-based medicinedDavid Sackett, MD 103

Table 6.7. This is a “best research design approach” to answer a specific

clinical question using a particular research design.
Clinical question Suggested research Design(s)
All clinical questions Systematic review, metaanalysis
Therapy Randomized controlled trial (RCT), metaanalysis
Also: cohort study, case-control study, case series
Etiology RCT, metaanalysis, cohort study
Also: case-control study, case series
Adapted from: Ackley BJ, Swan BA, Ladwig G, Tucker S. Evidence-based nursing care guidelines:
medical-surgical interventions. St. Louis, MO: Mosby Elsevier; 2008:7.172

Ultimately, as per Straus and Sackett “Firstly, practicing EBM begins and ends
with clinical expertise.”173 EBM is seen as a way to improve medical practice by
limiting errors even when there is no evidence to identify the gold standard of treat-
ment. By asking questions and searching for the best alternative among all the
various alternatives available, thousands of authors working with the Cochrane
Collaboration worldwide have fashioned systematic reviews to lower ambiguity
in medical decision-making. The conclusions and deductions from the Cochrane re-
views of RCTs influence their recommendations for clinical practice and
research.174 About 10 years ago, a rigorous system of evaluating data was introduced
by the Oxford Centre for Evidence-Based Medicine specifying the quality of the
methodology.168
“Evidence-based medicine has not been universally accepted in all quarters of
medicine and surgery.”
In a letter to the editor published in 2018 entitled:
“Rethinking Evidence-Based Medicine (EBM) in Plastic and Reconstructive
Surgery,” N.F. Al Deek175 argued against EBM as follows:
“Evidence-based medicine is not without weakness; it is inherently restrained by
the quality of evidence in the literature, affected by the timing of proposal of the
technique, experience of the operator, instruments used, anatomical understand-
ing, and volume, and the list goes on.”
Near the close of the editorial, he continued as follows: “If comparison must be
made, let it be among experts, not among a pool of data.”175
While advancing, in our opinion, a contrary and a most rational view, Dr. Eric
Swanson of Leawood, Kansas, said:
“Evidence-based medicine is our true North Star. It ranks data over institu-
tional authority, consensus of experts, mainstream views, and the tyranny of
conventional wisdom .... Evidence-based medicine empowers the pioneer to
challenge the status quo on an even playing field, where only the facts matter.
Let us not abandon but rather recommit to our scientific roots . surgeons
attend medical schooldnot a fine arts academy or business school for a reason.
If we turn our backs on evidence-based medicine now, not only will we fail, but
we will deserve to fail.”176 (Bold italics added)
104 CHAPTER 6 Brief history of evidence-based medicine—David Sackett, MD

On the other hand, arthritis researchers Peter Croft et al.177 in the United
Kingdom, while discussing the pros and cons of EBM thought that criticism of
EBM needed to be openly expressed and freely discussed. They thought that the pro-
ponents of EBM needed to accept clinical expertise especially in the area of innova-
tion. They believed that inventiveness and new ideas could be rationally resolved.
“by allowing the use of the new, innovative interventions at an early stage within the
setting of RCTs, or observational, monitoring, or audit studies.” The alternative is to
define characteristics of interventions or situations that would be acceptable as ex-
ceptions to EBM.177
Others saw EBM primarily as a guide to excellence in the clinical decision pro-
cess by integrating expertise with patient preferences thereby improving medical
practice especially avoiding errors when a specific gold standard is not available.
But these authors were also concerned about the implied suppression of innovation,
pointing out that the most deleterious aspect of EBM is when it operates as an excuse
to:
“.block the access of the innovation to patients certainly not the best way to
maximize the benefits of EBM”178
Colleagues from McGill University, Montréal, Québec, Canada, division of car-
diology, department of medicine, clearly recognized the aim of EBM was to facili-
tate the physician’s ability to make rational clinical decisions based on superior
knowledge from RCTs and metaanalysis. However, the reality is, as they pointed
out, evidence from RCTs is frequently imperfect, incongruous, contradictory, or ev-
idence is nonexistent, even for clinical questions which have been scrupulously stud-
ied. They reminded us that the likelihood of therapeutic success or failure of a given
therapy is not identical in all the individuals treated in any specific trial because re-
sults from any trial cannot be assuredly applied to every other individual patient.
This is true even if that patient matches all the entry benchmarks for the particular
trial in question. They went on to say that important sources of knowledge come
from guidelines; however, there are limits to the quality and the transferability of ev-
idence, so physicians and surgeons nevertheless require rational thought, “clinical
reasoning” to select the “best choices,” especially in the absence of complete knowl-
edge, decisions must be made. So, Sniderman and colleagues recognized that we are
ultimately left with:
“Clinical reasoning is the pragmatic, tried-and-true process of expert clinical
problem solving that does value mechanistic reasoning and clinical experience
as well as RCTs and observational studies. Clinicians must continue to value clin-
ical reasoning if our aim is the best clinical care for all the individuals we
treat.”179
In the middle of last century, Dr. Harry Bakwin of New York City wrote an inter-
esting inquiry into some of the then contemporary pediatric errors exploring the
various reasons for their perseverance. He adroitly referred back to Sir Thomas
Brown’s huge 17th century treatise entitled Pseudodoxia Epidemica, which is
 Brief history of evidence-based medicinedDavid Sackett, MD 105

illuminated as the “Enquiries into very many received Tenents and commonly Pre-
sumed Truths.”180 Bakwin observed that Sir Thomas investigated the abundant fal-
lacies then acknowledged as truths of the day all the while authenticating their
absurdity.180 As we now know so well, science, in general, has debunked the
magical, the mystical, and the reigning superstitions that prospered during the
1600s. But even today, in our “modern scientific era,” there are practices and delu-
sions that endure in the practice of medicine despite their patent fallaciousness.
Think complete and total turbinectomy as a treatment for benign nasal airway
obstruction or that turbinate hypertrophy is a serious complication of deafness. Pseu-
dodoxia Epidemica could be rewritten today, in modern times of the 21st century, as
Pseudodoxia Rhinologica.
Recall the citation of T. Carmalt Jones* at a meeting of the British Medical As-
sociation chronicled in The Lancet in 1895 as follows:
“Removal of hypertrophied inferior turbinals and moriform growths should be
practiced in cases of deafness and tinnitus where the auditory nerve was in a
healthy condition.”78 (Bold italics added)
*Jones T. Carmalt. “Turbinotomy in cases of Deafness and Tinnitus Aurinm”: The Lancet 2.
The British Medical Association. August 24, 1895 p.496.
Generally, the medical profession acknowledges the adverse effects of flawed
teachings by experts, even professors who practice predominantly without any sci-
entific objective evidence, mainly possessing a wealth of “experience” enjoying to
be greeted by colleagues and christened by the exhalated term, “expert” or at med-
ical conferences as “esteemed professor.” Just as authorities once proclaimed the
healing power of leaches or bloodletting, major errors in contemporary medical rhi-
nologic education appear to be the failure to properly educate the student in the fun-
damentals of nasal physiology. For example, the ideas and opinions regarding upper
airway surgery were often based on observation alone while scientific knowledge
regarding the upper airway must of necessity be based on objective testing and
comprehension of the fundamental principles of physics incorporating and accepting
the aerodynamics of nasal airflow during both inspiration and expiration. The salient
concepts regarding the influence and physiologic realities of aerometry of both the
internal or external nasal valve are both fundamental and crucial knowledge for the
coherent cogent practice of upper airway nasal surgery.
Diagnosis and treatment concepts require evolution in scientific thinking, which
in our field seems to be painfully sluggish, inevitably accompanied by errors delay-
ing and at times derailing progress. No doubt, despite errors, progress requires iden-
tification and confirmation with substantiation of those identified miscalculations to
be reduced, for a steady arc of improvement, regrettably we must accept missteps.
We proclaim that progress is two steps forward and one step back. Dr. Bakwin180
perspicaciously noted that error-prone medical progress was already shrewdly
detected and reflected upon by the French critical essayist and author Marcel Proust
(1871e1922) who observed:
106 CHAPTER 6 Brief history of evidence-based medicine—David Sackett, MD

“For, medicine being a compendium of the successive and contradictory mistakes

of medical practitioners, when we summon the wisest of them to our aid, the chan-
ces are that we may be relying on a scientific truth the error of which will be
recognized in a few years’ time. So that’s to believing medicine would be the
height of folly, if not to believe in Medicine were not greater folly still, for from
this mass of errors there have emerged in the course of time many truths.”181
Dr. David L. Sackett died in May 2015, leaving behind a major philosophical in-
fluence on the clinical practice of medicine with his commanding concepts of EBM.
As a concluding statement on the matter, according to Dr. Sackett, EBM is really all
about the prudent use of contemporary “best evidence” from the literature to be used
in formulating rational decisions about the care of a particular patient. Practicing
EBM means incorporating three fundamental requirements:
1. Primarily, harvesting the “best scientific” research from the literature
2. That best research evidence must be combined with the physician’s unique
clinical expertise
3. Integrating the patient’s values, desires, and specific situation into the decision-
making process
In summary, for Dr. Sackett before a final therapeutic decision can be made,
those three requirements needed to be considered and integrated into the decision
process. Primarily and most prominent was the necessary fundamental research ev-
idence from the literature. Although research evidence was supreme, it required
coupling with the individual specific clinical circumstances (conditions) of a given
patient and eventually integrated with the unique individual patient’s preferences
before reaching a concluding clinical decision apropos of future action.
Recognize, moreover that the practice of EBM requires a physician’s lifetime
commitment to education and remaining abreast of the contemporary literature
regarding diagnosis, treatment, and prognosis for any given medical and surgical
condition.173
Ultimately, those of us in rhinology must accept the remaining reality that as of
March 2023, there were no studies listed for inferior turbinate reduction, turbinate
surgery, or turbinoplasty at the Oxford Centre’s database.168 Therefore, we need
to continue utilizing our rational clinical reasoning to manage the problem of nasal
airway obstruction secondary to inferior turbinate enlargement (“hypertrophy”);
cautious clinical reasoning, while minimalizing turbinate trauma in the absence of
definitive RCTs, is the order of the day, avoiding a catastrophic result for an innocent
trusting patient.
In answer to the question, why is EBM pertinent to our conversation in this text,
it’s because understandably, the most reliable treatment information, the best evi-
dence, comes from well-conceived and well performed RCTs; however, that is
not to say that all level IV evidence should be ignored and all level I evidence
accepted as fact. The LOEs provide a guide for us the reader, and we are required
to be cautious when interpreting these results.166
 CHAPTER

The turbinates—
management
7
1. Middle turbinate management
The debate regarding middle turbinate preservation has a heated history of disagree-
ment raging for more than a century, the rhinologic equivalent of the Hundred Years’
War, 1337e1453, in the blossom of the Middle Ages. Middle turbinate “resectors”
are surgeons who remorselessly rationalize resection of the middle turbinate to fore-
stall formation of synechia in the region of the middle meatus.182e184 Proponents on
the other side of the divide champion respecting not resecting the middle turbinate
for its importance as a critical anatomical landmark and as an independent functional
organ system.185e187
Among all the brother and sister surgeons, there are effectively two schools of
thought regarding managing the middle turbinate. Without wavering, all agree
that the middle turbinate dispassionately represents an important landmark in nasal
sinus surgery since the olfactory cribriform region is superior and medial to the mid-
dle turbinate. Lateral to the middle turbinate is a plethora, a surplus of important
structures including the frontal recess, the floor of the anterior cranial fossa, the mid-
dle meatus, semilunar hiatus, the uncinate process, the infundibulum, the maxillary
sinus ostium, the ethmoidal bulla, and the orbital contents. The medical literature
both favors and criticizes middle turbinate resection.182e187 So, what are we left
with?
For the historical record, the practice of middle turbinate resection was con-
demned by Professor Walter Messerklinger, MD, (1920e2001)185 the “father” of
modern endoscopic sinus surgery (ESS) and mentor to the incomparable surgeon
and educator, Professor Heinz Stammberger, MD, (1946e2018) of Graz, Austria,187
both favoring middle turbinate preservation whenever possible. They accepted a
“conservative” approach that embodied preserving a maximum aggregate of normal
tissue, whereas partial middle turbinate resection was tolerated only in cases of
concha bullosa and paradoxical middle turbinate.
Other surgeons promoted “routine” total or partial middle turbinate resection as a
fundamental step in essentially every endoscopic sinus operation. We think that
“routine” total or partial middle turbinate resection as a prelude to every sinus sur-
gery is “unreasonable”; we display computerized tomography (CT) scans from pa-
tients having had, in all “likelihood,” essential middle turbinate resections, who

Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00007-X 107

Copyright © 2024 Elsevier Inc. All rights reserved.
108 CHAPTER 7 The turbinates—management

developed “empty nose syndrome (ENS).” These middle turbinectomies were per-
formed elsewhere, not at the Mayo Clinic; seen in Figs. 7.1e7.4.

FIGURE 7.1
Coronal CT scan of a patient exhibiting the common findings of bilateral middle
turbinectomy seen in patients with the “empty nose syndrome,” performed elsewhere, not
at the Mayo Clinic. This procedure is not supported by authors.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

FIGURE 7.2
Coronal CT scan of a patient exhibiting the common findings of middle turbinectomy seen
in patients with the “empty nose syndrome,” performed elsewhere, not at the Mayo Clinic.
This procedure is not supported by authors.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
 1. Middle turbinate management 109

FIGURE 7.3
Coronal CT scan of a patient exhibiting the common findings of middle turbinectomy seen
in patients with the “empty nose syndrome,” performed elsewhere, not at the Mayo Clinic.
This procedure is not supported by authors.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

FIGURE 7.4
Coronal CT scan of a patient exhibiting the common findings of middle turbinectomy seen
in patients with the “empty nose syndrome,” performed elsewhere, not at the Mayo Clinic.
This procedure is not supported by authors.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
110 CHAPTER 7 The turbinates—management

In addition, we assessed and treated a patient for “ENS” after septectomy (squa-
mous cell carcinoma) and subtotal resection of a portion of the left lateral wall of the
nose who developed symptoms several years after the initial tumor surgery. Both
middle turbinates were resected with a partial reduction (subtotal resection) of the
left inferior turbinate. Note: the surgery was not performed at the Mayo Clinic, by
a Mayo Clinic surgeon. Fig. 7.5
Both approaches, preservation and resection of the middle turbinate have pro-
duced “successful” outcomes; nonetheless, there are various variables that have
not been controlled, so practically every study in the literature has their conclusions
based on nonrandomized retrospective assessments. Many, if not all, of these studies
probably have dubious conclusions and associated problematic prejudices.
The argument even included possible potential peril to the frontal recess result-
ing in an increased incidence of frontal sinusitis subsequent to partial resection of the
middle turbinate. In 1995, Swanson et al. at the University of Pennsylvania observed
a statistically significant rise in secondary frontal sinus disease when a portion or the
entire middle turbinate was surgically removed.188
Figs. 7.6 and 7.7 are examples of patients, seen at the Mayo practice, who devel-
oped secondary frontal sinusitis after previous middle turbinectomies, performed
elsewhere, not at the Mayo Clinic.

FIGURE 7.5
Coronal CT scan of a patient who developed symptoms of the “empty nose syndrome” after
septectomy and subtotal resection of a portion of the left lateral wall for squamous cell
carcinoma of the nasal septum. Both middle turbinates have been resected with a partial
reduction (subtotal resection) of the left inferior turbthee. Note: the primary surgery was
not performed at the Mayo Clinic or by a Mayo surgeon.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
FIGURE 7.6
Coronal CT scans of a patient who developed frontal sinusitis subsequent to a middle
turbinectomy. The CT scan on the left is prior to the middle turbinectomy, while the CT
scan on the right is taken some time after a bilateral middle turbinectomy, performed
elsewhere, not at the Mayo Clinic. This procedure is not supported by authors.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

FIGURE 7.7
Coronal CT scan of a patient who developed frontal sinusitis sometime after a bilateral
middle turbinectomy, performed elsewhere, not at the Mayo Clinic. This procedure is not
supported by authors.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
112 CHAPTER 7 The turbinates—management

Zhou and Li in a retrospective analysis (n ¼ 87) investigated the effect of partial

middle turbinectomy on the frontal sinus and concluded that partial middle turbinec-
tomy has no effect on the incidence of frontal sinusitis.189
In control a review of 155 consecutive patients, utilizing the “Duncavage tech-
nique” for partial middle turbinectomy, Fortune and Duncavage found a 10% inci-
dence of frontal sinusitis subsequent to partial middle turbinate resection.190
Havas and Lowinger attempted to resolve the debate by studying a population
composed of (n ¼ 1106) patients, some patients with (n ¼ 509) middle turbinate
surgery, and (n ¼ 597) patients without middle turbinate surgery. Their team
recorded few complications while lauding the benefits of thoughtful partial middle
turbinate resection in patients with extensive sinus disease.191 In a study from New
York University involving ethmoidectomy operations in 100 patients, conservative
partial middle turbinate resection was performed in 50 patients with preservation
of the middle turbinate in the other 50 patients. After a two-year follow-up, the:
“.clinical and endoscopic findings revealed no difference in the incidence of
frontal sinusitis or frontal recess stenosis between groups.”192
In a prospective study, (n ¼ 31) patients in 2003 from the University of Califor-
nia Los Angeles found that:
“.middle turbinate resection has no deleterious effects on the results of endo-
scopic sinus surgery.”193
So, if the middle turbinate is significantly involved with an inflammatory process
as with extensive polypoid disease and associated exposed bone, then resection is
advisable, since leaving a large “raw surface” has the potential for developing post-
operative adhesions. Remember, the turbinates are involved with the nasal cycle, the
maintenance of a proper airflow, in addition to warming and charging the inspired air
with moisture, the middle turbinate also contains some olfactory elements. Overall,
authorities agree that if extensive polypoid changes of the middle turbinate mucosa
are present, then partial resection of the damaged mucosa is indicated.194,195
Stewart in 1998 found that partial middle turbinate resection had a lower adhe-
sion rate when compared with total middle turbinate resection.196 In other words, the
presence of extensive polypoid degeneration with the destruction of a major portion
of the middle turbinate, concomitant with chronic rhinosinusitis (CRS), obviously
turbinate preservation is virtually impossible; therefore, cautious resection is almost
statutory.
As pointedly observed by Nurse and Duncavage,197 the kerfuffle and brouhaha
surrounding middle turbinate resection centers around any specific surgeon’s actual
approach or philosophy regarding nasal physiology and those opinions are currently
widely diverse, distinct, and disparate.
Fundamentally, we completely agree with Kennedy’s assertion that in the pres-
ence of a normal middle turbinate, then surgical resection is not necessary to access
either the ethmoid labyrinth or the frontal recess.194
 1. Middle turbinate management 113

Kennedy, Rice, and other experienced surgeons agree that the middle turbinate
should be partially resected removing extensive polypoid changes of that particular
middle turbinate when existent.193e198
In the presence of an airway obstructing middle turbinate concha bullosa, it is
universally agreed that some type of surgical intervention is indicated to reduce
the obstruction. For a concha bullosa, we favor incision into the body of the concha
bullosa with instrument collapse; thereby, minimizing the airway obstruction while
maintaining both the medial and lateral mucosal surfaces of the middle turbinate
structure since mucocele is rare Figs. 7.8e7.13.
So, what are we left with?
Remarkably after the searing perspicacious 2001 paper by Clement and White
who unequivocally specified that after judging 283 papers over a 35-year period
of both middle and inferior turbinate surgery that since there were no randomized
controlled trials (RCTs), not a one, specifying:
“The evidence supporting the efficacy of these procedures remains debat-
able.”199 (Bold italics added)
As of 2010, Scheithauer28 astutely noted while supporting Clement and White
unfortunately it was virtually impossible to make a clear recommendation regarding
middle turbinate preservation or excision due to the lack of controlled, long-term
randomized studies in the literature.

FIGURE 7.8
Coronal CT scan of a patient (from our practice) exhibiting the typical findings seen with
bilateral concha bullosa (both middle turbinates), right larger than the left.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
114 CHAPTER 7 The turbinates—management

FIGURE 7.9
Photograph of a #64 Beaver knife blade for incision into the anterior portion of the middle
turbinate in the process of reducing a concha bullosa.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

FIGURE 7.10
Illustration of a bone scissor cut into the body of the middle turbinate to reduce the
concha bullosa after the #64 Beaver knife blade incised the anterior portion of the middle
turbinate allowing for the introduction of the bone scissors.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
 1. Middle turbinate management 115

FIGURE 7.11
Illustration of a collapse of the middle turbinate, reducing the concha bullosa, with a
modified Ferris Smith forceps.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

FIGURE 7.12
Photograph of a Ferris Smith forceps (below) with the modified Ferris Smith forceps
(above) used specifically to collapse an incised concha bullosa of the middle turbinate.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).
116 CHAPTER 7 The turbinates—management

FIGURE 7.13
Coronal CT scan of a patient (from our practice) exhibiting the typical findings seen with
bilateral concha bullosa, on the left, note the inferior turbinates exhibiting evidence of the
nasal cycle on the right side is congested while the left is the decongested side. On the
right is a CT scan of the same patient one year after bilateral reduction (collapse, without
resection) of the concha bullosa of middle turbinates, preserving the nasal turbinate
mucosa.
(Kern and Friedman. By permission of Mayo Foundation for Medical Education and Research. All Rights Reserved).

Fortunately, for the middle turbinate debate, we have a recent, 2018 RCT by
Hudon and colleagues from Université de Sherbrooke, Sherbrooke, Canada, who
looked at the effect of preservation versus resection of the middle turbinate (middle
turbinectomy) on surgical outcomes after ESS for CRS200. In 16 patients, 15 males
(15 initial and primary cases), the nasal cavities were randomized:
“.so that middle turbinectomy was performed on one side while the middle
turbinate was preserved on the other. Each participant acted as their own con-
trol.” After 6 months follow-up, they concluded that there was: “.no sustained
objective endoscopic benefit of routine middle turbinectomy” in their 16 CRS
patients with polyposis after ESS.200 (Bold italics added)
Finally, for the moment, of “approximate temporary truth” in the absence of
certainty from RCTs, we champion saving the middle turbinate for both its physio-
logical function and as a critical anatomical landmark, especially for potentially
revision surgery in patients with CRS with recurrent polyps; therefore, unless
reduced or destroyed by polypoid disease concomitant to CRS, or a paradoxical mid-
dle turbinate, or a concha bullosa, for our crowd, preservation of the middle turbinate
is the word of the day. We favor discrete resection of middle turbinate polypoid dis-
ease and conservative surgical treatment of a concha bullosa as summarized and pre-
sented in Figs. 7.8e7.13.
 2. Inferior turbinate management 117

2. Inferior turbinate management

2.1 Classification: inferior turbinate enlargement (“hypertrophy”)
There are a number of published systems for classifying enlargement (“hypertro-
phy”) of the inferior turbinate.
Three are based on the clinical physical examination and one on CT. (201e204)
The nasoendoscopic system proposed by Camacho et al. is the most recent, 2015,
from the Stanford Outpatient Medical Center in Redwood City, California. It is a
validated grading system based on a study of 100 consecutive patients (200 inferior
turbinates) that were prospectively graded by two different individuals on two sepa-
rate occasions. Grading of the 200 inferior turbinates was as follows:
“.classified as a grade 1 when the inferior turbinate occupies 0% to 25% of the
total airway, grade 2 is 26% to 50%, grade 3 is 51% to 75%, and grade 4 is when
the inferior turbinate occupies 76% to 100%.”201 (Bold italics added)
Over 20 years ago, Friedman et al. proposed a simplified system using a three-
part grading system where:
Grade 1 is “normal” or slight enlargement of the inferior turbinate without
airway obstruction,
Grade 2 is partial airway obstruction, and
Grade 3 is complete obstruction of the nasal airway at the level of the inferior
turbinate.202
A study correlating the nasal anatomy to the severity of obstructive sleep apnea
classified inferior turbinate enlargement (“hypertrophy”) as: 0dnormal, 1dmild,
2dmoderate, or 3dsevere.203
By studying the inferior turbinate (concha) bone using CT, Uzun et al. rated the
inferior turbinate size as:
Type 1 (lamellar),
Type 2 (compact bone),
Type 3 (combined), and
Type 4 (bullous).204
Whichever classification of turbinate enlargement (“hypertrophy”) is your favor-
ite, we suggest using it during your clinical evaluations.

2.2 Turbinate reduction: surgical and nonsurgical procedures

Since the mid-1980s, during the evidence-based medicine (EBM) milieu, the
optimal study design for comparing therapeutic interventions is the unrivaled
RCT. In 2001, colleagues Clement and White from the Department of Otolaryn-
gology, University of Dundee, Ninewells Hospital and Medical School, Dundee,
United Kingdom, reviewed more than 500 papers covering 35 years identifying
118 CHAPTER 7 The turbinates—management

283 papers detailing turbinate surgery and noted a recent increase in the number of
endoscopic and laser turbinate procedures. Astoundingly, as previously mentioned,
there was a total absence of any RCTs among those papers for both middle and infe-
rior turbinate surgery.199 They concluded, somewhat sardonically, that this field of
clinical research is “driven by technological advancement rather than by establish-
ment of patient benefit."
Since the introduction of EBM about 30 years ago, the righteous clamor in oto-
rhinolaryngologic practice and academic circles has been for RCTs to determine
rational guidelines for achievable goals vis-à-vis the turbinates designed for a pre-
dictable benefit for our patients. Unfortunately, a dearth describes the quantity of
RCTs in both otorhinolaryngology and in the plastic surgery literature; however,
auspicious trends may be promising. 205e209 In 2009, Cleveland Clinic authors
Batra, Seiden, and Smith presented an exhaustive review of the current evidence
from 96 studies of inferior turbinate surgery containing a prodigious list of refer-
ences.210 They cited 93 (97%) of the 96 studies as level 4 or 5 with two level
2211,212 and only one of the highest order, level 1 study.26
Recently, in 2015, Peters et al. from University Medical Center Utrecht, Utrecht,
the Netherlands, went as far as to sneeringly brand the quality of the RCTs in our
ENT literature as “suboptimal.”213 (Bold italics added)
As of 2023, we ask, what are the comprehensive choices, evidence-based or
otherwise, available for the management of the inferior turbinate following a med-
ical treatment failure?
Based on the all-inclusive reviews of Hol and Huizing, (2000),25 Scheithauer,
(2010),28 Abdullah and Singh, (2021),214 we have integrated and modified their infe-
rior turbinate management framework with ours as: Inferior Turbinate Reduction:
Surgical and Nonsurgical Procedures 2022 Table 7.1.
Within our ecosphere, we hold that the triad of principal objectives or goals for
inferior turbinate treatment are:
1. Relief of nasal airway obstruction secondary to inferior turbinate enlargement
(“hypertrophy”)
2. Preservation of physiologic turbinate function
3. Avoidance of complications, immediate and delayed (hours, days, weeks,
months, and years into the future)
To grasp the entirety of turbinate management techniques utilized over the years,
there are principally two types of turbinate procedures: streamlined and simplified as
follows:
(a) Epithelial mucosal destruction: Transmucosal approach (including partial and
complete-total turbinectomy)
(b) Epithelial mucosal preservation: Submucosal approach
For a brief anatomy lesson, recall that the nasal mucosa (epithelium and submu-
cosa) itself is basically composed of two distinctive layers, the epithelium and the
submucosa (lamina propria, stroma) Fig. 5.2:
 2. Inferior turbinate management 119

Table 7.1 Inferior turbinate reduction: Surgical and non-surgical

procedures.a
A. Epithelial mucosal destruction (transmucosal approach)
1. Surgical resection-turbinectomy (partial or complete-total)
2. Electrocautery
3. Laser therapy
4. Cryotherapy
B. Epithelial mucosal preservation (submucosal approach)
1. Submucosal soft tissue surgical reduction (turbinoplasty)
a. Submucosal soft tissue reduction only
b. Conchal bone reduction only
c. Combined: soft tissue and conchal bone reduction
2. Microdebrider
3. Radiofrequency
4. Coblation
5. Ultrasound
6. Electrocautery
C. Complimentary: out-fracture (lateralization)
1. Solitary-isolated intervention
2. Combined with other procedures
a
Specifically, as previously written, surgery is: the medical practice of managing diseases, deformities,
and injuries by actually “cutting” into a part of the body, while, on the other hand, electrocautery,
chemocautery, lasers, radiofrequency, coblation, or ultrasound are not surgery in the traditional sense
of cold knife “cutting,” but nonetheless they are currently considered “surgery” by some authors;
however, we choose to call these practices the non-surgical Turbinate Reduction Adjunctive Pro-
cedures (n-s TRAPs).

1. EpitheliumdThe outer most epithelial layer composed of pseudostratified cili-

ated columnar respiratory epithelium consisting of ciliated columnar cells,
goblet cells, intermediate cells, and basal cells, resting on a basement
membrane.
2. SubmucosadThe second deeper layer is the submucosa (lamina propria,
stroma), which is composed of a loose connective tissue with a rich complex
vascular erectile venous sinusoid system along with seromucous glands and
mesenchymal cells.
Although “usually” effective in relieving nasal airway obstruction, the epithelial
mucosal destruction (including resection-partial and complete-total turbinectomy)
procedures have been associated with postoperative complications such as profuse
bleeding, pain, crusting, and ENS (paradoxically the procedure to relieve nasal
airway obstruction has been associated with exacerbating nasal airway obstruction)
with a protracted period for recovery.
Because untoward complications are largely avoided in the epithelial mucosal
preservation approach, epithelial mucosal preservation is our preference.
Currently, since numerous and various inferior turbinate reduction practices are
utilized worldwide, a comprehensive review and commentary regarding each
120 CHAPTER 7 The turbinates—management

surgical and non-surgical Turbinate Reduction Adjunctive Procedure (n-s TRAP)*

intervention is presented for completeness.
* Specifically, as previously written, surgery is: the medical practice of managing dis-
eases, deformities, and injuries by actually “cutting” into a part of the body, while, on the other
hand, electrocautery, chemocautery, lasers, radiofrequency, coblation, or ultrasound are not
surgery in the traditional sense of cold knife “cutting,” but nonetheless they are currently
considered “surgery” by some authors, but we choose to call these practices the non-surgical
Turbinate Reduction Adjunctive Procedures (n-s TRAP).
Different techniques, surgical and nonsurgical, have been used to increase the
cross-sectional diameter of the nasal airway by reducing the inferior turbinate
size, thereby enlarging (opening) the internal nasal valve area.25,28,211,214,216 These
techniques include conventional surgical turbinectomy (partial or complete-total) or
turbinate reduction using nonsurgical modalities such as electrocautery, lasers, and
cryotherapy. In addition, conventional (cold knife) turbinoplasty, microdebrider tur-
binoplasty, radiofrequency turbinoplasty, coblation turbinoplasty, ultrasound turbi-
noplasty, and submucosal electrocautery have all been introduced submucosally
reducing the turbinate size, thereby enlarging (opening) the internal nasal valve
area to improve nasal breathing.
Overall, these surgical and nonsurgical techniques are classified into two broad
categories:
First, the epithelial mucosal destruction
Second, the epithelial mucosal preservation
These techniques are based on the destructive damage or preservation of the
nasal epithelial mucosal surface of the inferior turbinate summarized in Table 7.1.
External surgical resection (turbinectomy-partial and complete) resects (excises
and removes) the entire epithelial mucosa (pseudostratified ciliated columnar respi-
ratory epithelium), including the submucosal (lamina propria, stroma) erectile tis-
sue, the neurovascular bundles, and conchal (turbinate) bone.
Turbinoplasty is an epithelial mucosal preservation technique that reduces the
submucosal soft tissue (lamina propria, stroma) with or without conchal (turbinate
bone) removal.
According to Silkoff et al. in Philip Cole’s unimpeachable impeccable nasal
airway laboratory at the University of Toronto, Canada, nasal obstruction secondary
to inferior turbinate enlargement (“hypertrophy”) can be objectively and accurately
quantitated with both active anterior rhinomanometry and acoustic rhinometry.215
These twin techniques have become the first-line routine standard methods to objec-
tively confirm nasal airway obstruction.214
In general, indications for surgical or nonsurgical reduction of the inferior turbi-
nate are considered sensible after 3 months of medical therapy that is unable to
resolve the nasal airway obstruction secondary to usually bilateral turbinate enlarge-
ment (“hypertrophy”) regardless of etiology.28
 2. Inferior turbinate management 121

2.2.1 Epithelial mucosal destruction: Transmucosal approach (including

partial and complete total turbinectomy)
1. Surgical resection-turbinectomy (partial or complete-total)
2. Electrocautery
3. Laser therapy
4. Cryotherapy
For precision, turbinectomy is defined as the removal of a portion of the turbinate
(partial turbinectomy) or the entire turbinate, complete (total turbinectomy) and may
be performed with or without endoscopic visualization. Elwany and Harrison
compared partial turbinectomy against three other types for inferior turbinate reduc-
tion evaluating subjective and objective outcomes for comparison.117 They found
both partial turbinectomy and laser turbinectomy superior to inferior turbinoplasty
and cryoturbinectomy for relieving nasal airway obstruction, by reducing resistance
to nasal airflow and improving olfaction. Muco-ciliary clearance was unchanged
postoperatively. Those patients with partial turbinectomy despite an “improved”
nasal airway developed postoperative nasal pain, headache, mucosal atrophic
changes, and postoperative bleeding more frequently than the patients in the other
three randomly assigned study groups who were evaluated one year posttreatment.
In two important papers, 1999 and 2003, Passali et al. reported on long-term
(four and six years) outcomes in (n ¼ 382) patients randomly assigned to six
different treatment groups:211,216
1. Electrocautery (62 patients)
2. Cryosurgery (58 patients)
3. Laser surgery (54 patients)
4. Submucous resection without lateral displacement (69 patients)
5. Submucous resection with lateral displacement (94 patients)
6. Turbinectomy (45 patients)
After data collection (n ¼ 382) and analysis, Passali et al. concluded that:
“After six years, only submucosal resection resulted in optimal long-term normal-
ization of nasal patency and in restoration of mucociliary clearance and local
secretory IgA production to a physiological level with few postoperative compli-
cations (p < .001). The addition of lateral displacement of the inferior turbinate
improved the long-term results. We recommend, in spite of the greater surgical
skill required, submucosal resection combined with lateral displacement as the
first-choice technique for the treatment of nasal obstruction due to hypertrophy
of the inferior turbinates.”211
They found that while inferior turbinectomy reduced nasal airway obstruction, it
was associated and coupled with additional complications including, remarkable
pain, nasal crusting, and excessive bleeding. As was plainly pointed out by Abdullah
and Singh214 referencing Chhabra and Houser21 declaring:
122 CHAPTER 7 The turbinates—management

“. that atrophic rhinitis and the empty nose syndrome are now acknowledged
as delayed sequalae following total turbinectomy.”214 (Bold italics added)
Numerous authors2e4,18e28,214 have made these observations that significant
nasal turbinate trauma may lead to dryness and nasal crusting, which can develop
after disrupting the normal mucociliary activity, shredded raw mucosal edges along
with exposed bare bone all leading to secondary atrophic rhinitis and the ENS years
into the future. ENS may result from surgical excision or from other traumatic turbi-
nate injuries effected by electrocautery, laser, or cryosurgery. These observations of
significant nasal turbinate trauma leading to delayed nasal atrophy and ENS may
appear years after the inciting trauma has been appreciated and has been reported
by various and abundant eyewitnesses.2e4,18e28
Passali et al. also noted that while turbinectomy had its major favorable effect on
nasal breathing (objective test results from rhinomanometry and acoustic rhinome-
try), the functional effect was unfavorable with a parade of findings involving:
abnormal mucociliary transit times, abnormal secretory IgA testing, and an increased
incidence of secondary hemorrhage, which ultimately hinders the utility of total
turbinectomy, banishing its station as a rational therapeutic preference.211,216
Their data strongly supported submucosal resection (turbinoplasty) plus out-
fracture (lateralization) of the inferior turbinate as the treatment of choice, since
this results in excellent nasal airflow while maintaining nasal functional integrity
with the slightest probability of future complications.
Electrocautery when applied as electrical current induces unpredictable damage
to the epithelium and submucosa depending on the duration and voltage of the cur-
rent and is the least effective mode of improving nasal airway resistance; addition-
ally, there is an increased rate of crusting and synechiae.211
As named by Abdullah and Singh214 for inferior turbinate reduction, the lasers
regularly used are diode and CO2 lasers such as neodymium-doped: yttrium
aluminum garnet (Nd-YAG), holmium: YAG, potassium titanyl phosphate, and
argon plasma lasers which are cited in the literature.214,217
Essentially the laser varieties are centered on their manner and method of appli-
cation, for example: “.contact or noncontact mode, pulsed or continuous wave
emission, emitted wavelength, and output power.”218 According to the literature,
the preferred choice is the diode laser as it allows accurate cutting of the inferior
turbinate tissue coupled with excellent hemostatic control.218 A RCT comparing
radiofrequency with the diode laser reduction of airway obstruction found that the
patients had a significant improvement of nasal breathing for both diode laser and
radiofrequency application 3 months after treatment. Although there were no major
complications observed, patients in the radiofrequency arm complained of signifi-
cant discomfort.219 With a colossal patient population (n ¼ 3219), Prokopakis
et al. compared three study arms including CO2 lasers, radiofrequency, and electro-
cautery turbinate reduction treatments with a subjective (visual analog scale, VAS)
and objective (rhinomanometry) measurements. Mucociliary transport disturbances
 2. Inferior turbinate management 123

and difficulties in manipulating the device were the only significant drawbacks of
using the CO2 lasers, but all three groups had outstanding postoperative breathing
results, without statistical differences, reported at one month and one year
posttreatment.220
Cryotherapy is considered minimally invasive, using either liquid nitrogen or
nitrous oxide as the thermal freezing agent initiating necrosis with extensive damage
of surface epithelium of both the nasal mucosa and submucosal stromal tissue. Since
the quantity of tissue reduction was unpredictable and the beneficial results where
unsustainable cryosurgery was eventually discarded.211

2.2.2 Epithelial mucosal preservation: Submucosal “turbinoplasty”

approach
1. Submucosal soft tissue surgical reduction (conventional “cold knife”
“turbinoplasty”)
(a) Submucosal soft tissue reduction only
(b) Combined: soft tissue and conchal bone reduction
(c) Conchal bone reduction only
2. Microdebrider
3. Radiofrequency
4. Coblation
5. Ultrasound
6. Electrocautery
Principally, all the epithelial mucosal preservation (submucosal “Turbino-
plasty”) treatments are directed toward the submucosal stroma containing erectile
neurovascular bundles.

2.2.2.1 Submucosal soft tissue surgical reduction (conventional “cold

knife” “turbinoplasty”)
2.2.2.1.1 Submucosal soft tissue reduction only All these procedures are intended
to remove the obstructive submucosal stromal portion of the inferior turbinate,
largely at the anterior head, which is the posterior portion of the internal nasal valve
area. The goal is reduction of the submucosal stromal tissue thereby reducing
obstruction of the critical internal nasal valve area, improving breathing all the while
preserving as much of the stromal tissue as possible so as not to interfere with phys-
iologic functions. All these treatments are basically termed “turbinoplasty” ap-
proaches. Only the submucosa is removed claiming the advantage over the other
turbinate procedures by preserving sufficient overlying mucosa, while removing
adequate amounts of obstructing tissue to improve the airway sufficiently and signif-
icantly to improve breathing without reducing nasal function.
Another term labels this technique a “submucosal” resection or treatment, refer-
ring to the submucosal stromal location of the reduction treatment procedure. It was
Mabry91 who used the term “inferior turbinoplasty” that involved directing the treat-
ing modality below the epithelial mucosal surface within the inferior turbinate,
124 CHAPTER 7 The turbinates—management

affecting only the submucosal stromal tissues with or without removing part of the
conchal (turbinate) bone.
2.2.2.1.2 Combined: soft tissue and conchal bone reduction Occasionally, the
inferior conchal (turbinate) bone is remarkably thickened and obstructing requiring
reduction of the bone in addition to reduction of the submucosal stromal soft tissues.
Mabry said that he utilized the procedure for more than nine years, and he did not
observe any of the formally dreaded complications such as bleeding, foul odor,
discharge, crusting, and by extension secondary atrophic rhinitis in any of his study
population (n ¼ 40). His histologic studies of “inferior turbinoplasty” patients,
observed five years postoperatively, as expected, revealed normal epithelial mucosal
surfaces with submucosal stromal fibrosis along with a decreased mucous gland
population.91
2.2.2.1.3 Conchal bone reduction only On very rare occasion, the conchal bone
may be extremely thick and readily seen on direct CT scan. In this situation, the
thicken conchal bone can be successfully reduced with a dental drill without compli-
cation as has been experienced by the Mayo team (EBK) on one occasion.
Many modalities can be utilized for performing the “inferior turbinoplasty.”
Methods and instruments used to accomplish a turbinoplasty may include any one
of a host of options: “cold knife,” microdebrider, radiofrequency, coblation, ultra-
sound, and even electrocautery; something, anything to reduce the subepithelial sub-
mucosal stromal tissues for the relief of nasal airway obstruction. Some of the
submucosal techniques are, of course, blind with obvious limitations as the tissue
removal is inexact; therefore, tissue reduction is frequently imprecise.
Various designs and methods of “inferior turbinoplasty” compared to other ther-
apeutic modalities have been offered to the profession. From our literature review
and subsequent to Abdullah and Singh’s comprehensive paper in 2021, we located
the pertinent literature supporting the physiologic and therapeutic logic of the “infe-
rior turbinoplasty,” which has happily and overwhelmingly captured the data-driven
class of rhinologists.214,221e229

2.2.2.2 Microdebrider
The microdebrider deserves special mention as a significant advancement coupled
with the endoscope, which allows aspiration of the hematogenous dissemination
(blood) permitting precise tissue removal sparing the overlying epithelium, entirely,
with minimal thermal damage to the surrounding tissues.221,225
Subjective and objective evaluations are currently common practice including
symptom questionnaires, endoscopic scoring, and acoustic rhinometry which
revealed microdebrider turbinoplasty as a superior method for accomplishing nasal
airway relief lasting beyond a year.221e225 In another outcome study, objectively us-
ing anterior rhinomanometry, patient’s nasal breathing resistance calculations were
substantially reduced after endoscopic microdebrider inferior turbinoplasty.226
Other authors presented a matched study comparing conventional turbinoplasty
with microdebrider turbinoplasty which exhibited (n ¼ 46) substantial reduction
in both blood loss and operative times compared to conventional turbinoplasty.228
 2. Inferior turbinate management 125

In a study by Cingi et al., microdebrider turbinoplasty (n ¼ 124) was compared with

radiofrequency turbinoplasty (n ¼ 144), while symptom improvement was statisti-
cally significant in the microdebrider group and the objective rhinomanometric mea-
surements demonstrated increased nasal airflow, improved breathing, in the
microdebrider group when compared to the radiofrequency group; nonetheless, us-
ing the power instrument microdebrider still has the inherent risk of intraoperative
and or postoperative bleeding.230

2.2.2.3 Radiofrequency
Radiofrequency turbinoplasty is a minimally invasive method that accomplishes
precise and pointed turbinate volume reduction using radiofrequency energy at an
estimated temperature range of 60 C (140 F) to 90 C (194 F), while electrocautery
temperatures reach a range of 400 C (752 F) to 600 C (1112 F). Radiofrequency
lessens tissue injury, minimizing surrounding tissue trauma, and reducing posttreat-
ment pain.214 In addition to pain reduction, there is a reduction in turbinate tissue
bulk, reducing nasal airway obstruction, thus improving nasal breathing.230e235 Rhi-
nomanometric measurements were markedly improved validating an increased nasal
airway breathing. The few sequalae noted included negligible epistaxis, some dry-
ness, little crusting, or inconsequential adhesions.234,235 In two separate studies
comparing microdebrider turbinoplasty with radiofrequency turbinoplasty, the in-
vestigators found markedly improved nasal airflow with objectively improved rhino-
manometry scores similarly improved VAS showing that both techniques are
treatment successes. As expected, the only noted downside was impaired mucocili-
ary transport function with the conventional turbinectomy.236,237
In 2012, Garzaro et al. compared radiofrequency turbinate reduction (n ¼ 26)
with partial turbinectomy (n ¼ 22) finding that while both techniques improved
breathing, radiofrequency turbinoplasty preserved nasal physiology more efficiently,
as anticipated, than partial turbinectomy and was deemed the superior method of
choice for reducing inferior turbinate enlargement (hypertrophy).238
Interestingly, in another study using the Nasal Obstruction Symptom Evaluation
scale, developed by the American Academy of Otolaryngology Head and Neck Sur-
gery, as a validated way for comparing different treatments of patients with nasal
airway obstruction. Although the patient follow-up was merely 6 months, both pa-
tient groups had septal deviations and inferior turbinate hypertrophy and those
treated by radiofrequency turbinoplasty alone had similar results with those who
were treated by a combined radiofrequency turbinoplasty and septoplasty. Of course,
the explicit surgical details and the passage of adequate time, measured in years, are
required before uttering any definitive statements with any legitimacy.239

2.2.2.4 Coblation
Coblation (“controlled ablation” meaning tissue reduction in a precise “controlled”
manner or “cold ablation” meaning tissue reduction by a lower or “colder” temper-
ature) is radiofrequency energy supplied in a saline or lactated Ringer’s solution that
energizes the sodium and chloride ions producing a plasma field which decreases the
126 CHAPTER 7 The turbinates—management

thermal tissue trauma, thereby reducing postoperative pain, accelerating recovery.214

By vaporizing and destroying the submucosal neurovascular erectile tissues, the
turbinate volume is reduced by the contracting fibrosis of the healing process, which
is maintainable well into the future. Passali et al. accomplished coblation turbino-
plasty in (n ¼ 40) patients collecting preoperative data repeated at one and three
years postoperatively. Using a VAS for subjective data and active anterior rhinoman-
ometry and acoustic rhinometry for objective data, they noted that both coblation
and radiofrequency provided an improvement in nasal airflow. Complications
were reduced to just trivial bleeding and minor crusting. Notably, together coblation
and radiofrequency were less painful, especially in the immediate postoperative
period compared to other procedures; however, while both methods reduced nasal
airway obstruction, improving breathing, the effectiveness decreased through
time, over their three-year study interval.240
The outcome of both radiofrequency and coblation was better than conventional
turbinoplasty with fewer and less severe complications than conventional turbinec-
tomy.214 The short-term excellent coblation effects seen at 3 months by Farmer et al.
were objectively and subjectively recorded by rhinomanometry and by a VAS
score.241 In a longer study of 32 months, Leong et al. studied the effect of coblation
in a limited population, starting with 18 patients reduced to 13 patients using objec-
tive posterior rhinomanometry and subjective VAS. The nasal breathing was statis-
tically significantly improved objectively (p ¼ .033), but the subjective calculations
did not attain statistical significance.242
Most recently, in 2020, Singh et al.243 compared coblation-assisted turbinoplasty
(CAT) with microdebrider-assisted turbinoplasty (MAT) in a prospective compara-
tive trial. Patients (n ¼ 33) were randomized for coblation CAT (n ¼ 16) and micro-
debrider treatment MAT (n ¼ 17). Evaluation was by a VAS for nasal obstruction,
sneezing, rhinorrhea, headache, and hyposmia. Turbinate size, edema, and secre-
tions were assessed by endoscopic examination. The assessments were done preop-
eratively, at the first postoperative week, second and third postoperative months.
Their recorded postoperative sequalae included pain, bleeding, crusting, and syne-
chiae. The authors concluded that both procedures were able to improve symptoms
equally by effectively eliminating the enlarged submucosal neurovascular erectile
soft tissues jointly with the conchal bone exclusive of complications.243

2.2.2.5 Ultrasound
Ultrasound technology, with its destructive capability, was somewhat new to the rhi-
nology community in 2010. So, it was most intriguing and very refreshing to read the
paper by Gindros et al. who gifted the profession with a prospective RCT using ul-
trasound for inferior turbinate treatment.27 They presented (n ¼ 60) patients diag-
nosed with nonallergic chronic hypertrophic rhinitis; separated into two groups:
Group 1: 30 patients, using ultrasound treatment on the left side and monopolar
electrocautery on the right.
 2. Inferior turbinate management 127

Group 2: 30 patients, using radiofrequency coblation treatment on the left side

and ultrasound on the right.
Subjective evaluation for nasal breathing and pain was attained using a VAS.
Objective evaluation was achieved by both active anterior rhinomanometry and
acoustic rhinometry. Data collected before treatment and 1, 3, and 6 months post-
treatment documented both subjective and objective improvement in all cases.
The best results were obtained with the ultrasound procedure, secondly with the
radiofrequency technique. They decided, after data assessment, that the ultrasound
treatment was safe, secure, and superior to both the radiofrequency and electrocau-
tery group as the electrocautery group demonstrated the smallest improvement.27

2.2.2.6 Electrocautery
As is well known, when electrocautery is performed submucosally, blindly into the
inferior turbinate, the amount of tissue destruction is impossible to estimate and
there is considerable risk of soft tissue and conchal bone thermal damage that
may ultimately result in a secondary osteomyelitis. Doubtless, it is not difficult to
grasp that adverse and significant thermal trauma may result from a “prolonged”
or “elevated” voltage applied to the surrounding submucosal neurovascular erectile
stromal tissues and to the conchal bone of the inferior turbinate. Remember that the
electrocautery temperatures reach a range of 400 C (752 F) to 600 C (1112 F). As a
consequence of imprecision and the chance of significant thermal damage, we do
not recommend using electrocautery for a submucosal approach for treating turbi-
nate enlargement.

2.2.3 Complimentary out-fracture (lateralization) techniques

1. Solitary-isolated and sole intervention: out-fracture (lateralization)
2. Combined with other procedures
Out-fracture (lateralization) of the inferior turbinate may be performed as a
solitary-isolated and sole intervention or alongside all the other turbinate reduction
techniques, except of course when the turbinate is appallingly and dreadfully
deleted, expunged, as in the case of total turbinectomy.
Out-fracture (lateralization) involves lateral displacement of the inferior turbi-
nate usually first by an initial in-fracture, moving it medially toward the midline
septum from its normal connection to the lateral wall of the nose. The mechanical
anatomical concept for this procedure is creating added space when the inferior
turbinate is lateralized away from the midline which permits opening (enlarging)
the region of the head of the inferior turbinate, which is the posterior portion of
the internal nasal valve area.5 Many surgeons believe that inferior turbinate’s out-
fracture (lateralization) efficacy is variable, causing criticism over its long-term util-
ity as there is a propensity for the inferior turbinate to return to its original position
after out-fracture (laterization), so some surgeons do not recommended it as a single
procedure, but it may be used to supplement the other techniques.211,214,216
128 CHAPTER 7 The turbinates—management

2.2.3.1 Solitary-isolated and sole intervention: out-fracture

(laterization)
According to Hol and Huizing,25 Killian introduced out-fracture (laterization-
lateropexia-conchopexy) because of the adverse effects of total inferior turbinec-
tomy and Kressner, in 1930, introduced crushing of the inferior turbinate with
specific forceps followed by trimming and his method has since been recycled
and reused by several surgeons including usual use at their own institution in The
Netherlands.2 For the record, as has been pointed out previously by Farmer and
Eccles142 although the inferior turbinate thickening results from submucosal
vascular congestion, interstitial tissue edema, and at times conchal bony thickening
or even undisputable genuine microscopic cellular hyperplasia, but most often there
is no proof of cellular hypertrophy despite the common use of the term “turbinate
hypertrophy.”142 They suggest that the term “turbinate hypertrophy” is imprecise
and should be changed to “turbinate enlargement.” Naturally, the primary pathology
producing the inferior turbinate enlargement needs accurate diagnosis for appro-
priate management.
Hol and Huizing also pointed out that out-fracture (laterization) is relatively risk-
free, preserves function, is technically simple although they thought that it tends to
resume its original position concluding that out-fracture (laterization) may best
serve as complementary when combined with other procedures25,86
Moss et al.244 from Division of OtolaryngologyHead and Neck Surgery Univer-
sity of California, San Diego San Diego, California, performed a systematic litera-
ture review in 2015 writing in Viewpoints in Plastic and Reconstructive Surgery
thought the superbly designed studies for inferior turbinate out-fracture (lateraliza-
tion) came from the authors, Aksoy et al. in 2010,245 Marquez et al. in 1996,246 and
Passàli el al. 2003.211,216 It was Aksoy et al. who studied out-fracture (lateralization)
alone in a prospective study (n ¼ 40), 80 turbinates which showed convincing evi-
dence that out-fracture was durable at 1 and 6 months postseptal and turbinate sur-
gery with CT evidence of fixed bony change. According to Moss et al., in another
prospective study (n ¼ 21), the out-fractures were durable supported by statistically
significant rhinometric data presented by Marquez et al.246 Buyuklu et al., including
one of our former visiting surgeons to Mayo Clinic, Dr. Ozcan Cakmak from the De-
partments of Otorhinolaryngology and Radiology, Baskent University Faculty of
Medicine, Ankara, Turkey, studied CT scans of out-fractures (lateralization) as a
solitary-isolated turbinate intervention in septal surgical patients (n ¼ 10), 20 turbi-
nates. Based on their persuasively documented CT scans, they concluded, as did
Moss et al., that out-fracture (lateralization) can be effortlessly performed, effective
in improving the nasal airway, and what’s more, it’s a reliably durable procedure for
inferior turbinate surgery.247

2.2.3.2 Combined with other procedures

It was Passali et al. in 1999 and 2003, respectively, (n ¼ 382) who confirmed (at four
and six years follow-up) that turbinoplasty accompanied with an out-fracture (later-
alization) is an effective approach to inferior turbinate enlargement (“hypertrophy”)
 2. Inferior turbinate management 129

when compared to electrocautery, cryotherapy, laser cautery, turbinectomy, and sub-

mucosal resection without an out-fracture (lateral displacement).211,216
In their most compelling randomly assigned prospective study, Passali et al. used
subjective and objective measures (acoustic rhinometry, anterior rhinomanometry,
mucociliary transport time, and secretory immunoglobulin A levels) to confirm
the superiority of turbinoplasty with an out-fracture (lateralization) over all other
methods studied.11,216
English authors found that by adding the uniquely multiple submucosal out-
fractures (lateralization) of the inferior turbinates to turbinoplasty, results were
improved, although not statistically significant the trend was “improvement,”
arguing that the additional steps appeared to improve the outcomes without addi-
tional risk of complications.248
On the other hand, other English authors added to the dilemma by their anterior
rhinomanometry findings, (n ¼ 28), that out-fracture (lateralization) with amputa-
tion of the posterior ends (tips) of the inferior turbinates failed to demonstrate any
improvement in the nasal airway.249 Though just over half the patients had an objec-
tive improvement in nasal airflow, only half of this group reported a subjective
improvement in their symptoms.
The Chinese added to the out-fracture (lateralization) discussion with a paper in
2013 in which the inferior turbinate “hypertrophy” was documented by both endos-
copy and CT scan in a total of (n ¼ 50) patients.250 Supporting the out-fracture
(lateralization) debate with statistical data assessments (t-test and correlation tests)
of the subjective VAS and the objective studies (acoustic rhinometry and rhinoman-
ometry), these authors concluded that out-fracture (lateralization) was an “ideal sur-
gical method” to improve nasal airway function secondary to an expanded nasal
cavity.
A few years later, in 2016, Sinno and colleagues presented conflicting data chal-
lenging the notion that out-fracture (lateralization) was an “ideal surgical
method.”251 Publishing in Plastic and Reconstructive Surgery, they performed a sys-
tematic review of 58 surgical papers involving surgical treatments for inferior turbi-
nate “hypertrophy” covering total turbinectomy, partial turbinectomy, submucosal
resection, “turbinoplasty,” laser surgery, cryotherapy, electrocautery, radiofrequency
ablation, and turbinate out-fracture (lateralization).251 After their careful systematic
review of operative results and complications, they concluded that submucous resec-
tion (turbinoplasty) with radiofrequency ablation was the superior method of treat-
ing turbinate “hypertrophy” and that out-fracture (lateralization) should only be used
in combination with tissue-reduction procedures . They also noted that:
“.turbinectomy (partial/total) and submucosal resection showed crusting and
epistaxis at comparatively higher rates, whereas more conservative treatments
such as cryotherapy and submucous diathermy failed to provide long-term
results.”251
130 CHAPTER 7 The turbinates—management

A year later, in a very shrewd retrospective study in transnasal transsphenoidal

brain tumor patients (n ¼ 55), Lee and colleagues questioned whether out-fracture
(lateralization) was permanent or not.252 They were especially interested in these
practices since inferior turbinate out-fracture (lateralization) was practiced alone
or in concert with other procedures in rhinoplasty patents. Using coronal CT images
scans for conchal bone objective measurements, they answered their question, yes,
“inferior turbinate out-fracture is preserved for at least 6 months.”
In addition, they noted that subsequent to out-fracture (lateralization), the thick-
ness of the medial mucosa increased, which supports the idea that turbinoplasty plus
out-fracture (laterization) is perhaps the treatment of choice for inferior turbinate
enlargement (“hypertrophy”). This is yet another study supporting the idea that infe-
rior turbinate out-fracture (lateralization) is possible to be maintained (durable) con-
trary to finding of other surgeons. Obviously, the exact and specific details of any
out-fracture (lateralization) technique make a meaningful difference and probably
answers the question of discrepancy.
For a comprehensive coverage of the turbinate subject, Hol and Huizing25 also
presented the out-fracture (lateralization) “discarded” techniques of Fateen and
Legler using the terms lateropexia (or conchopexy). Conchopexy is the procedure
where the inferior turbinate is displaced (out-fractured) into the maxillary sinus
through a large inferior meatal antrostomy. This technique was generally unpopular;
therefore, eventually abandoned.
Additionally, Golding-Wood’s vidian neurectomy of the 1980s was also “dis-
carded” since it only controlled the nasal secretions but did not alter the nasal airway
obstruction (breathing difficulty).25
The work of Salam and Wengraf114 was fascinating as (n ¼ 25) patients were
randomly chosen as to which side would receive a total inferior turbinectomy, while
the other side received a conchoantropexy. At 6 months after surgery, as expected,
there was no statistically significant differences in relief of nasal airway obstruction
between the two sides. However, 16% of the patients experienced dryness and crust-
ing on the side of the total turbinectomy(p < .05), which was statistically signifi-
cant; yet separately and strikingly, there was a higher incidence of postoperative
pain (p < .05) on the total inferior turbinectomy side, whereas these findings did
not occur on the conchoantropexy side since the turbinate mucosa was preserved
intact on that side.252
Out-fracture (lateralization) is fundamentally free of peril; however, some ques-
tions did arise regarding the effect of out-fracture (lateralization) on the ostiomeatal
unit complex and a possible “silent sinus syndrome.” These intriguing questions
were answered by Lee and colleagues who demonstrated in a number (n ¼ 23) of
patients that out-fracture does not adversely affect the ostiomeatal unit complex
in anyway.253 In 2011, Jung and Gray presented a case of a unilateral silent sinus
syndrome in a 41-year-old man attributed to a prior (6 months previously) bilateral
out-fracture (lateralization) procedure concomitant to a septorhinoplasty.254 Frac-
ture of the orbital floor is the usual cause of silent sinus syndrome, which is
 2. Inferior turbinate management 131

characterized by enophthalmos and hypoglobus secondary to a prolapse of the

orbital contents into the maxillary sinus.
Another interesting question was answered by measuring the nasolacrimal transit
time after inferior turbinate out-fracture (lateralization) and radiofrequency ablation.
Twenty patients with septal surgery and unilateral out-fracture (lateralization) had
nasolacrimal transit times measured by the saccharine test, which was totally
normal at 2 months postsurgery in all 20 patients.255
We close this section citing studies celebrated above, Passali et al.,11,216 Moss
et al.,244 Aksoy et al.,245 Marquez et al.,246 Buyuklu et al.,247 Zhang et al.,250 and
Lee et al.252 that inferior turbinate out-fracture (lateralization) is possible to be main-
tained (durable) for a prolonged period of time and may be safely combined with
other turbinoplasty procedures on the inferior turbinate.
One of us (EBK) has performed multiple closed comminuted fractures of the
inferior turbinate (conchal bone) on multiple occasions over many years that has
been sustained (durable) over a prolonged period of time, measured in years
(anecdotal).
It is technically possible to create multiple closed comminuted fractures, espe-
cially when the out-fracturing (lateralization) begins in close proximity to the origin
of the inferior turbinate, at the lateral maxillary wall. In this instance of multiple
comminuted fractures of the inferior turbinate (conchal bone), internal nasal dress-
ings (“packs” of various lengths of ½ inch gauze soaked in antibiotic and steroid so-
lution) are introduced after intranasal septal stents are sewn in place. Both “packs”
and stents are removed after approximately 7 days. This practice supports the find-
ings of Passali et al.,216 Moss et al.,244 Aksoy et al.,245 Marquez et al.,246 Buyuklu
et al.,247 Zhang et al.,250 and Lee et al.252 that an inferior turbinate out-fracture
(lateralization) is possible to be maintained (durable) for a prolonged period of time.
In order to accurately assess and evaluate any specific surgical technique, the
exact and defined details of any operative procedure, specifically the out-fracture
(lateralization) technique, must be clearly presented in an unambiguous and explicit
meaningful manner, so it can be precisely visualized and duplicated, then for bias
reduction and efficacy, a well-designed and well-performed RCT is vital and
authoritative.

2.2.4 Histopathology
Lately, in 2016, an elegant and sophisticated ultrastructural histopathologic study
was presented by the Italian academic investigators Neri et al.256 They examined
the ultrastructural features (scanning electron microscope for cell surfaces and trans-
mission electron microscope for intracellular and extracellular spaces) of the nasal
mucosa after Microdebrider-Assisted Turbinoplasty (MAT) in seven patients with
two normal controls.256 The tissues were obtained preoperatively then at 4 months
and again at four years after surgery and processed for transmission electron micro-
scopy.256 At 4 months, the nasal mucosa appeared normal with normal pseudostra-
tified ciliated columnar respiratory epithelium with normal cellular morphology.
The submucosa was also normal as the interstitial edema disappeared. At four years,
132 CHAPTER 7 The turbinates—management

tissue was again acquired, observed, and confirmed that the normal cellular architec-
ture was restored. Neri and colleagues specified that after “cold knife” excision
mucosal basal cells can proliferate and repair the injury. They noted:
“.that p63 gene plays a central role in the epithelial stem cell self-renewal
although critical information on the properties of nasal epithelial stem cells is
lacking.”256
These authors explicitly reminded us that the nasal mucosa is physiologically
involved with two equally important and distinct functions: the defensive immune
response function and the breathing (respiratory) function of providing airway resis-
tance (‘resistor function’dthe internal nasal valve area for breathing, lung expan-
sion, and enhancing venous return) and of air conditioning (‘diffusor function’
dturbulent air flow) of charging the inspired air with warmth and humidification
by the mucus from the seromucous glands and goblet cells.256 Furthermore, the
nasal mucosal cells have the defensive power to fuel IgE production and liberate im-
munoglobulins IgA and IgG, leukotrienes, histamine, prostaglandins along with
interleukin (Il) cytokines including the all-important Il-4, Il-5, Il-8, and Il-13.
The nasal epithelium (pseudostratified ciliated columnar respiratory epithelium)
is the physical barricade against pathologic organisms and particulate matter gaining
entrance to the lower airway. The submucosa (lamina propria, stroma) also has a
meaningful functional contribution through the venous sinusoid vascular system
and a vibrant cellular defensive system including the dendritic cells which present
foreign proteins to T and B lymphocytes to initiate immune responses. Other specific
defensive cells include eosinophils, mast cells, basophils, plasma cells, and the anti-
microbial proteins all proceeding and presiding in the submucosal vascular
system.15e17,256
Because the nasal mucosa (epithelium and submucosa) has a multitude of signif-
icant functional commitments, many surgeons side with those of us who campaign
for the preservation of the nasal mucosa, as much as possible, during any type of
inferior turbinate surgery saving nasal functioning tissue avoiding the possible un-
favorable unsavory sequalae, from a radical turbinate terminator, resulting in the
ENS.256 So, they strongly favor cold knife reduction of an enlarged “hypertrophic”
inferior turbinate avoiding any thermal injury to the epithelium and the submucosa
since:
“Thermal techniques cause coagulation of venous sinuses resulting in fibrosis
and scarring of the submucosal tissue. Gindros et al. found loss of cilia after sub-
mucous diathermy. Ultrastructural changes after radiofrequency include squa-
mous metaplastic epithelium with basal cells and lack of ciliated, brush cells
and columnar cells, fibrosis of the lamina propria, intense inflammatory infiltra-
tion, and reduction of seromucous glands. It was demonstrated also that thermal
techniques cause nerve fibers devitalization resulting in reduced sensation of
nasal airflow.”256
 2. Inferior turbinate management 133

The paper of Gindros et al.257 cited by Neri et al.256 is significant since they also
examined all specimens by electron microscopy comparing monopolar diathermy,
radiofrequency coblation, and ultrasound in 60 patients, divided into two groups
of 30 with a diagnosis of airway obstruction secondary to chronic nonallergic infe-
rior turbinate “hypertrophy.” Gindros et al. studied these tissues before and at 1, 3,
and 6 months after treatment. In the pretreatment study of “hypertrophic” tissue,
they observed a global degeneration of epithelial cells, ciliary loss, disrupted and
disordered intercellular connections, edema, nasal mucus overproduction, and in-
flammatory cell infiltration. After intervention with monopolar diathermy and radio-
frequency coblation, the histopathologic findings included a reduction of both
intercellular edema and reduced mucus production with a degenerated disorientated
epithelium, yet an exuberant assembly of collagen, by another name, vigorous sub-
mucosal fibrosis. On the other hand, after ultrasound treatment in some patients, they
observed islets of normally organized ciliated columnar cells appearing in the
epithelium. They concluded that in several cases treated with ultrasound, epithelial
regeneration occurred:
“. resulting to anatomical and functional restoration of the nasal
physiology”257
In an earlier histopathologic paper, Berger and colleagues noticed that when the
inferior turbinate mucosa is hypertrophied, histological examination reveals a gener-
alized increase of the submucosal width (of the lamina propria, stroma) with venous
sinusoid vascular engorgement, with the associated gross external thickening of the
mucosa overlying the medial portion of the turbinate accounting for the gross
increased turbinate size.258 The submucosal glandular elements and vessels in the
surrounding connective tissue in the submucosa (lamina propria, stroma) basically
remain unchanged. It is imperative that after turbinate treatment, the mucociliary
transport blanket be preserved by protecting the mucosal surface epithelium, the
pseudostratified ciliated columnar respiratory epithelium, so normal ciliary clear-
ances are maintained. In another histopathologic study, Berger et al. looked at
two groups or patients specifically examining the epithelium and the submucosal
tissues:259
Group 1: Coblation treatment n ¼ 16 (22 samples)
Group 2: Control inferior turbinectomy treatment n ¼ 14 (18 samples)
After coblation, qualitative analysis displayed marked fibrosis with the depletion
of submucosal glands and venous sinusoids in the lamina propria. The coblation
group exhibited an increased connective tissue and a significantly (p < .001)
decreased fraction of both the submucosal glands and venous sinusoids. A signifi-
cantly decreased proportion of intact epithelium and a significantly increased rela-
tive proportion of partial epithelial shedding (p ¼ .03 and p ¼ .04, respectively).
The long-term histological effects of coblation of the inferior turbinate resulted in
partial epithelial shedding, probably due to the thermal submucosal vascular damage
of the lamina propria stroma, with significant fibrosis generating glandular and
venous sinusoid depletion.259
134 CHAPTER 7 The turbinates—management

With our physiological thinking, any practitioner pursuing inferior turbinate

reduction has the duty, responsibility, and obligation to preserve the pseudostratified
epithelial mucociliary transport system, minimize damage to the submucosal (lam-
ina propria, stroma) neurovascular morphologic structures avoiding adverse physi-
ologic consequences and the resultant sequalae all the while improving the nasal
airway breathing function.
Consequently, “cold knife” techniques appear to have the edge for now, avoiding
thermal trauma as submucosal vascular choking fibrosis also deprives the overlying
epithelium with the necessary nutrition to maintain a healthy mucociliary transport
system, and the secretory deprivation robs the requisite moisture needed to charge
the inspired air with heat and moisture allowing optimal exchange of oxygen and
carbon dioxide at the alveolar level.
All studies need the great equalizer, the final arbitrator, “Father Time,” to “weigh
in” before making a “final” adjudication regarding our interventions. Duration after
treatment matters before a “final” therapeutic result can be determined and “final”
promulgation for therapeutic recommendation. With duration in mind, the 2016
work of Pelen and associates while laudable and praiseworthy comparing the
“cold knife” microdebrider reduction with radiofrequency ablation concluded that
both techniques were minimally invasive and could reliably provide an improved
nasal airway subjectively and objectively assessed as statistically significant without
any disruption of nasal physiology.260 The only issue of concern and disquiet was
one of duration. Their posttreatment follow-up was, in their own words:
“Nasal obstruction, the grade of turbinate hypertrophy, and other symptoms were
evaluated with subjective nasal obstruction scale and anterior rhinoscopy before
the operation, and 3 days, 7 days, 4 weeks, and 8 weeks after the surgical inter-
vention.”260 (Bold italics added)
Certainly, projecting the long-term effects of a given procedure based on after
8 weeks of treatment results is a startling speculative leap of faith, for “who knows”
where that leap will land you?
 CHAPTER

How do you find the “Best

Reduction Method” for
inferior turbinate
enlargement
8
(“hypertrophy”)
reduction?

1. A Context with discussion of some specific critical

confounding questions
As we all know too well, when medical therapy fails to reduce an enlarged inferior
turbinate, a “surgical” reduction is advocated.
Is there clear agreement, any unanimity of unswerving direction, a signposting as
to the “best method” the “gold standard,” that one shining technique from the liter-
ature, for inferior turbinate reduction? The answer to the that question is a
resounding “possible perhaps.”
And that’s because of all the five superior level 1 papers reviewed by Larrabee
and Kacker264 they thought that the findings of the randomized trial (n ¼ 382) of
Passali et al.211,216
“.was the most effective at decreasing nasal obstruction caused by inferior
turbinate hypertrophy.”264
Therefore, to strictly and decisively answer the question of what is the “best
method,” a well-designed and well-performed randomized controlled trial (RCT)
is needed to confirm or contradict the randomized trial of Passali et al.211,216
So, in the meantime, what’s a rhinologist to do?
In 2001, as previously cited, the doctors from the United Kingdom, Clement and
White did not find any RCTs in their MEDLINE literature review of 35 years of infe-
rior and middle turbinate surgery, declaring that properly conducted RCTs were
essential to establish long-term benefits from turbinate treatment.199 After the chal-
lenge issued by Clement and White in this new era of evidence-based medicine
(EBM) for “properly” conducted RCTs, Batra et al. in 2009 did an evidence-
based review focusing on the inferior turbinate in adults finding only one level 1
Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00008-1 135
Copyright © 2024 Elsevier Inc. All rights reserved.
136 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

and two level 2 reports in their PubMed database search assessing 143 abstracts and
included 96 articles in their report.210 They thought that, in the future, all studies
should include control groups and must be prospective in design. In discussing
EBM’s emphasis on levels of evidence, they designated the hierarchy of levels of
evidence (level 1 the highest) from the literature as:
Level 1: RCTs
Level 2: prospective cohort study or low-quality randomized trials
Level 3: retrospective case-control studies
Level 4: case series or retrospective chart review
Level 5: case reports or expert opinion
They reviewed 143 international studies including turbinectomy, lasers, thermal
techniques, and turbinoplasty. They commented that although level 1 evidence from
RCTs is the highest level of evidence, that an RCT may not be necessary since all
inferior turbinate interventions gave an overwhelming initial positive response for
airway reduction, improved breathing, citing the parachute paper of Smith and
Pell demanding common sense when considering risk and benefits from various pro-
cedures and that an RCT may not be required for every study to be valid when the
result is obvious, an RCT is not required to realize that parachutes are effective in
reducing injury following jumping from airplanes.261
A year later, Leong and Eccles clearly recognized, for the moment, that no clear
directive for patient selection for inferior turbinate surgery existed because inferior
turbinate treatment was still evolving and definitive evidence regarding the “best”
treatment technique remained unresolved; therefore, prospective studies, RCTs,
with validated objective and subjective outcome measures appropriately controlled
were mandatory to answer the question, what is the best method for reducing an infe-
rior turbinate to improve nasal airway breathing?262
Over the next decade, some astute authors repeatedly reviewed the literature in
the leading ear, nose and throat (ENT) journals evaluating the level of evidence of
RCTs and concluded that essentially the quantity and quality of all the RCTs in
the ENT literature could be improved.205,207,263

1.1 Randomized controlled trials searching for the “Best Reduction

Method” from the literature
In 2014, Larrabee and Kacker from the Department of Otolaryngology New
York-Presbyterian/Weill Cornell Medical College, New York asked the question:
Which inferior turbinate reduction technique best decreases nasal airway
obstruction?264
They reviewed and presented the results of five superior papers they thought had
the most convincing level 1 data for effective reduction of nasal airway obstruction
secondary to enlargement (“hypertrophy”) of the inferior turbinate. All their level 1
 1. Discussion of some specific critical confounding questions 137

presented papers are listed below falling into the category of “possible perhaps” as to
a “Best Reduction Method” for inferior turbinate enlargement (“hypertrophy”):
1. Passali F, Passali G, Damiani V, Bellussi L. Treatment of inferior turbinate hy-
pertrophy: a randomized clinical trial. Ann Otol Rhinol Laryngol. 2003;112:
683e688.211
2. Nease C, Krempl G. Radiofrequency treatment of turbinate hypertrophy: a
randomized, blinded, placebo-controlled clinical trial. Otolaryngol Head Neck
Surg. 2004;130:291e299.26
3. Liu CM, Tan CD, Lee FP, Lin KN, Huang HM. Microdebrider-assisted versus
radiofrequency assisted-inferior turbinoplasty. Laryngoscope. 2009;119:
414e418. https://doi.org/10.1002/lary.20088.235
4. Cingi C, Ure B, Cakli E, Ozudogru E. Microdebrider-assisted versus
radiofrequency-assisted inferior turbinoplasty: a prospective study with objec-
tive and subjective outcome measures. Acta Otorhinolaryngol Ital. 2010;30:
138e143.230
5. Gindros G, Kantas I, Balatsouras D, Kaidoglou A, Kandiloros D. Comparison of
ultrasound turbinate reduction, radiofrequency tissue ablation and submucosal
cauterization in inferior turbinate hypertrophy. Eur Arch Otorhinolaryngol.
2010;267:1727e1733.27
After reviewing those level 1 papers, Larrabee and Kacker concluded with the
best practice:
“Of conventional inferior turbinate reduction techniques, submucosal resection
combined with lateral displacement is the most effective at decreasing nasal
obstruction caused by inferior turbinate hypertrophy. In the turbinoplasty group,
based on the current evidence, microdebrider-assisted and ultrasound turbinate
reduction have been shown to be the most effective. A prospective randomized
trial comparing the microdebrider-assisted and ultrasound turbinate reduction
has not yet been performed. Little research exists on the ultrasound procedure;
thus, the microdebrider-assisted turbinate reduction technique has the advantage
of more widespread familiarity.”264 (Bold italics added)
Since Larrabee and Kacker challenged the profession to perform a RCT
comparing ultrasound turbinate reduction with microdebrider-assisted turbinoplasty,
we searched the literature for that study to no avail. To our knowledge, such a study
has yet to be published, last searched for on the first of March 2023.

1.2 Future studiesddesigning the “Best Study” for finding the

“Best Reduction Method”
The constructive challenge commanded by numerous authors asserted that all
future turbinate studies should be randomized with control groups, RCTs, which
must be prospective in design following the philosophic principles of
EBM.199,205,207,210,262,263,265
138 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

So, what are the essential elements necessary to design the “Best Study” for
determining the “Best Method” for inferior turbinate reduction?
Taking the lead from Hol and Huizing,25 Batra et al.,210 Leong and Eccles,262
Agha et al.,266 and Peters et al.,215 we added some thoughts to their suggestions con-
cerning creating the criteria for an “ideal” or a “Best Study,” which includes the
following for clarity, consistency, and transparency in crafting an RCT that will
definitively answer the question as to the “best method” for inferior turbinate
reduction.

1.3 Thoughts for designing a “Best Study” for finding the “Best
Reduction Method” for treating patients with inferior turbinate
enlargement (“hypertrophy”)
1. Funding source(s)dtransparency with a conflict of interest (COI) statement
2. Ethical considerationsdinstitutional review board approval (when appropriate)
and compliance with principles included in the Belmont Report,* NIH
guidelines,* AMA’s Code of Medical Ethics guidelines, and the World
Medical Association-Declaration of Helsinki Ethical Principles for Medical
Research Involving Human Subjects
3. Informed written consent
4. Prospective study with clearly written and available “approved” protocol
5. Careful selection of primary and secondary endpoints to determine efficacy
6. Clear and easy to use case report form(s)
7. Protocol deviations (notated if and when they occur)
8. Randomly assigned treatment groups
9. Baseline demographics and clinical characteristics of each group
10. Blinding when feasible (note: blinding is possible in surgical and procedural
studies when the operator remains “silent” as to his/her specific involvement
with subjective and objective outcome studies performed by blinded
evaluators-coded study)
11. Matched control groupdmedical therapy group (blinding) and surgical and/or
procedural group(s)
12. Eligibility: inclusion and exclusion criteria
13. Adequate sample sizedprestudy power analysis
14. Statistical analysis with statistician involveddP values and confidence
intervals
15. Drop-out rate and cause(s)
16. Adverse eventsddata details and specifically mentioning if adverse events did
not occur
17. Histologydlight and electron microscopy (scanning and transmission electron
microscope)
Coded samplesdblinding pathologist to study purpose
18. Follow-up period minimum one year extending to 10 years with retrospective
study evaluation at a later date
 1. Discussion of some specific critical confounding questions 139

19. Pretreatment and posttreatment evaluation of:

(a) Endoscopic classification of turbinate enlargement (“hypertrophy”)
(b) Validated scores: Coded samples or study-blinding technician as to study
methods and purpose
1. Subjective visual analog score (VAS)
2. Subjective Snot-25 score or NOSE scale
3. Objective measurement of nasal airway pressure/flow changed
rhinomanometry-coded study
4. Objective measurement of nasal airway dimensionsdacoustic
rhinometry-coded study
(c) Mucociliary transport times measurement-coded study
(d) Secretory IgA measurements-coded study
(e). Olfaction evaluation (subjective and objective)-coded study
20. Interpretation of results with primary and secondary outcomes within context of
“current” evidence
21. Study weaknesses freely and clearly presented
22. Blinding of all third-party evaluators-coded
*Ethical principles in research with human participants:
1. Belmont report (1979) entitled: Ethical Principles and Guidelines for the Protection of Human
Subjects of Research. The National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research.
2. The National Institute of Health (NIH) Clinical Center researchers published seven main
principles to guide the conduct of ethical research:
Social and clinical value.
Scientific validity.
Fair subject selection.
Favorable riskebenefit ratio.
Independent review.
Informed consent.
Respect for potential and enrolled subjects.

1.4 When are randomized controlled trials NOT needed?

With the rigor of the “Best Study” design for finding the “Best Method for treating,
we, the authors of this book, totally support: How to design the “Best Study” for
finding the “Best Method” for treating patients with enlarged inferior turbinates?
Allowing physicians to make intelligent treatment decisions based on the best
data of the day has been the history of medicine “evidence first” is the way to
progress.
Although “evidence first” is the way to progress and EBM is the sacred “holy
grail” of modern medicine with the RCT the epitome of study design, there are
many clinical situations where common sense reigns and RCTs are not required
as pointed out by Smith and Pell261 and Paul Glasziou with coauthors267 who noted
some stark examples in medicine where RCTs were not needed calling them
140 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

“historical examples of treatments with dramatic effects” with a “Top 10” list listed
below alphabetically:
1. Blood transfusion for severe hemorrhagic shock
2. Closed reduction and splinting for fracture of displaced long bones
3. Defibrillation for ventricular fibrillation
4. Drainage for pain associated with abscesses
5. Ether for anesthesia
6. Insulin for diabetes
7. Neostigmine for myasthenia gravis
8. One-way valve or underwater seal drainage for pneumothorax and hemothorax
9. Suturing for arresting hemorrhage
10. Tracheostomy for tracheal obstruction
These are our “Top 10” examples of such dramatic effects, as Glasziou et al.
reasoned, that biases can be unambiguously ruled out without the need for RCTs.
They defined the dramatic effects by “the size of the treatment effect (signal) relative
to the expected prognosis (noise).”267
Nonetheless, we think that for a definitive answer to the question, what is the best
method for treating inferior turbinate enlargement (“hypertrophy”)? a well-designed
and well-performed RCT is needed to confirm or contradict the randomized trial
(n ¼ 382) of Passali et al.211,216

1.5 Asking answerable questions: empiricism versus rationalism

Practicing intelligent EBM, according to Kenny et al.268 revolves around asking
answerable clinical questions; the soul of EBM by:
(a) Framing a specific and clear-cut clinical question
(b) Searching for the best evidence in the literature
(c) Critically evaluating the evidence
(d) Integrating the evidence with clinician’s clinical capability coupled with the
unique features of the patient and their situation, expectations, and rights
(e) Evaluation of the clinician’s performance
The now former chief editor of the Mayo Clinic Proceedings Bill Lanier, MD and
his colleague S. Vincent Rajkumar discussed the medical applications of the two ma-
jor competing philosophies of empiricism and rationalism.269 Empiricism is based
on observational experimentation, research evidence in the Western tradition of
Francis Bacon, John Locke, David Hume, and others, while rationalism is that
method of gaining knowledge through intellectual reasoning, in medicine (clinical
judgment).
Empiricism is knowledge, from facts, evidence from experimentation, while
rationalism is knowledge, from intellectual reasoning, from experience, it’s clinical
judgment.
 1. Discussion of some specific critical confounding questions 141

EBM rationally favors empiricism, but what happens when new information rea-
ches the clinician and before deciding what action is demanded and defensible, the
clinician needs time for reflection with decision modulated by rational thought. As in
the case when clinical decisions require action, but evidence is limited, incomplete,
inconclusive, conflicting, or starkly nonexistent. What about inconclusive conflict-
ing poorly performed RCTs? What to do then? Rationalism to the rescue. The
reasonable belief approach employs the good “clinical judgment” idea and the apho-
rism from Canadian physician Kerr Lachlan White, MD (1917e2014) “Good judg-
ment comes from experience; experience comes from bad judgment.”270
Bad judgment, well-known and lamentable, has occurred in medicine often
without maliciousness of forethought. Once conventional and notable treatments
promulgated by experts have been overturned, invalidated, and abolished by
employing the scientific method, medical progress ensues. In an astounding 2013
article, Vinay Prasad and colleagues from the NIH reviewed over 2000 articles
with the intent of determining which medical practices have no benefit for the pa-
tients.271 We quoted from their abstract because of the authority of their findings;
provides pause for reflection:
“We reviewed 2044 original articles, 1344 of which concerned a medical prac-
tice. Of these, 981 articles (73.0%) examined a new medical practice, whereas
363 (27.0%) tested an established practice. A total of 947 studies (70.5%) had
positive findings, whereas 397 (29.5%) reached a negative conclusion. A total
of 756 articles addressing a medical practice constituted replacement, 165
were back to the drawing board, 146 were medical reversals, 138 were reaffirma-
tions, and 139 were inconclusive. Of the 363 articles testing standard of care, 146
(40.2%) reversed that practice, whereas 138 (38.0%) reaffirmed it.” And they
concluded: “The reversal of established medical practice is common and occurs
across all classes of medical practice. This investigation sheds light on low-value
practices and patterns of medical research.” 271(Bold italics added)
With this powerful paper, it is understandable that Prasad favors the rigor of sci-
ence since so many medical practices have been reversed (40.2%) over the years of
their study. EBM and RCTs are the orders of the day, empiricism over rationalism.
Agreed.
Wait, not so fast. What about uncertainty? How do we manage our patients then?
Prasad in Letters to the Editor of the Mayo Clinic Proceeding conceded but:
“There will always be a place for the thoughtful deliberation of physicians in
medicine; however, I continue to believe that given the pressures of the modern
marketplace and university promotions, most decisions should be firmly grounded
in RCTs powered for hard end points.”272
142 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

In the same issue, Donald G. Ross, MD wrote a response to Prasad in Letters to

the Editor; the debate is a foot:
“Medical research cannot be held to the same standard as basic science, but we
must remain aware of the (relative) weakness of the evidence we rely on in
applying ‘evidence-based’ principles. There must always be a place for rational
decision making based on experience and the situation of the individual patient.
Survival curves for 2 different therapies that appear nearly identical to the eye are
in fact nearly identical, even if complex statistics show a ‘significant’ difference
between them. I find that this line of reasoning is upsetting to some of my col-
leagues; they are looking for certainty where there are only probabilities. How-
ever, the diagnosis and treatment of the individual patient will always involve
making choices with some degree of uncertainty, and one must make one’s peace
with that.”273

1.6 Are controlled trials (RCTs) really needed? Can they actually be
accomplished in a surgical setting?
What about the role of EBM especially RCTs in the clinical practice of surgery espe-
cially when evaluating new procedures? The thoughtful approach addressing these
questions was tackled in a comprehensive manner, about 30 years ago, by Professor
of Obstetrics and Gynecology Gordon M. Stirrat and his colleagues from the United
Kingdom.274 They understood that all new surgical procedures must, for ethical rea-
sons, be assessed comparing the new to the contemporarily accepted method(s). Not
to make the comparison between the new procedure and the currently accepted
method was clearly unethical. They noted examples, from the surgical literature,
where less scrupulously evaluated procedures were eventually found to be ineffec-
tive. Gastric freezing for bleeding was eventually found to be harmful. Of course,
they recognized that the optimum comparison method was by an RCT, which is ideal
for a medication trial because drug trials could be an RCT that is double-blinded and
placebo-controlled. However, for evaluating a new surgical technique or for the
reevaluation of any surgical technique, there are major issues to consider for
randomization in surgical practice:
(a) Factually, a truly placebo operation is the unethical “sham operation,” which must
never be performed. Although this position is debated by Franklin G. Miller,
PhD on page 149. Surgical trials are rarely ever fully placebo-controlled.
(b) Blinding the surgeon for the procedure can never be achieved.
(c) In trials comparing new methods with established techniques, the surgeon’s
experience strongly determines results, inevitably results will be “better” for
the standard method and not directly comparable to the new method especially
with “learning curve” concerns. Further bias accrues because new surgical
techniques are often originated by fervently skilled surgeons, while the stan-
dard technique is performed by the balance of the surgeons in that specialty.
Stirrat et al. concluded by accepting the reality that the ideal double-blind
placebo-controlled trial cannot easily be applied for surgical comparisons. But the
 1. Discussion of some specific critical confounding questions 143

optimal design of RCTs for surgery must be attempted, nonetheless with input from
epidemiologists and/or statisticians.274
They presented a table listing suggested absolute and relative criteria for a valid
RCT.274
(a) Absolute criteria for a valid RCT
1. Random allocation mandatory
2. Trial size large enough to avoid erroneously false-positives or false-negative
outcomes
3. The number of patients required in each study arm must be large enough to
demonstrate a treatment effect and must be determined in advance of the
study starting
4. No alteration of the protocol is permitted without justification and
documentation
5. Approval of an ethics committee
6. Informed consent from patients before randomization
7. Analysis of results on the basis of “intention to treat”
As long as the absolute criteria are met, other questions may be asked.
(b) Relative criteria for a valid RCT
1. Although not always possible, every effort must be made to create the RCT
2. The “first patient” should be randomized
3. For large or controversial trials, an “independent data monitoring commit-
tee” can be useful
Dr. Stirrat noted that traditionally, surgical practice was formulated on the funda-
mental concepts and understanding of anatomy and pathophysiology of disease.275
In essence, surgery was rational and technical, scientific and artistic, so with the
emergence of the new paradigm of EBM and its reliance on RCTs, it was soon
recognized that the data from these scientific studies did not possess generalizability.
By definition, generalizability is a measure of how useful the results of a study are
for a broader group of people or situations.
At the dawn of the innovative movement of EBM with RCTs, about 25 years ago,
the critique, by the eminent Sir Nick Black, MD who served as the first Chair of the
UK Health Services Research Network at the Department of Health Services
Research and Policy at the London School of Hygiene and Tropical Medicine,
was that the scientific evidence from an RCT was not generalizable. In other words,
because the study results data were not widely transferable from the broad study
population to a specific unique individual surgical patient, surgeons lost their enthu-
siasm, excitement, and zeal for the essence of EBM, the RCT.276 Sir Nick Black
thought that:
“although EBM clearly has a place, it does not have all the answers.”276
Stirrat makes the distinction and reason for the inevitable tension between the
“clinical surgeon” dedicated to a unique specific patient in the present, in the here
144 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

and now, and the “clinical researcher” dedicated to the benefit of some patient some-
where and sometime in foreseeable future.275 Writing in the Journal of Medical
Ethics, Dr. Stirrat, in 2002, emphasized that medical intervention and new surgical
procedures still require justification by the “best available evidence.”275 Therefore,
RCTs are nevertheless needed and quite possible in surgery by well-designed and
well-performed RCTs.

1.7 Evidence first, but what to do when RCT data are limited,
incomplete, inconclusive, conflicting, or starkly nonexistent?
In the “evidence first” approach argued by Prasad,272 that despite its acknowledged
limitations, the “evidence first” worldview is the patented prescription designed for
progress in medicine. Prasad continues the argument by asserting that physicians
must not remain neutral, that choice is required, its either “evidence first” or “clin-
ical judgment.”272 Sniderman et al. contended that in the hurly-burly of everyday
clinical practice, in the atmosphere of uncertainty, when data from an RCT are either
not available or limited, incomplete, inconclusive, conflicting, or starkly nonexis-
tent, then “clinical judgment” (“clinical reasoning”) is compulsory to save the
day.180 Prasad and Sniderman et al. agree that when comparing the two worldviews,
empiricism versus rationalism, there is no substitute for “clinical judgment” (“clin-
ical reasoning”) to “fill in the gaps” while waiting for “the answers” in the current
EBM era.180 Is there a middle ground between empiricism versus rationalism
regarding optimal patient care? Our view of optimal patient care, especially in an
atmosphere of uncertainty, centers around a nonpolarized position, a sort of “bicam-
eral” duality approach, we suggest; employ empiricism when results of RCT trials
are available and use the rationalism of “clinical judgment” when trial data of an
RCT is just not available or limited, incomplete, inconclusive, conflicting, or starkly
nonexistent. In our opinion, empiricism and rationalism should cohabit in the same
physician, with the pendulum swinging “to and fro,” depending on the unique clin-
ical condition calling for decisions.
As suggested by Prasad et al.,271
of the 146 verified and validated medical practices that were reversed (discon-
tinued), no doubt, at first, those practices seemed logical and exquisitely
rational when in fact they were ultimately flawed.
As recently, in 2021, Tim Darsaut, MD a university neurosurgeon in Edmonton,
Canada, and Jean Raymond, MD a university interventional neuroradiologist in
Montréal, Canada, pointed out, reiterating the ethical medical care credo that care
must be empirical, that ethical care is based on reliable, repeatable, established in-
terventions with proven patient outcomes, essentially EBM, yet what to do in an at-
mosphere of uncertainty, when unproven interventions may either be useless or even
harmful.
What is the ethical approach in those cases of comparing validated care and
unvalidated care with its atmosphere of uncertainty? Of course, still guided by
 1. Discussion of some specific critical confounding questions 145

medical ethics, how to approach a patient or subject of a trial of a promising test or

unproven intervention until they are validated as valuable and helpful and not the
reverse? In the case of uncertainty, Darsaut and Raymond persuasively argued
that medical ethics demands that a clear distinction be made between “research”
and “care.” That a “separation” between the two to protect patients from “research”
studies designed to aid future patients.
Ethically, unvalidated care must be offered in the context of a “care research”
trial protocol to optimize the potential benefits while minimizing possible adverse
effects.277 They propose pragmatic “care research” trials integrated into clinical
practice to fulfill this need. Practicing good ethical medicine within the context of
uncertainty was their main concern; therefore, the distinction was made between
validated care and promising unvalidated care offered within the clearly announced
pragmatic “care research” design which is proposed to: “act in the best medical in-
terest of the patient.” So, they concluded that any new or unvalidated care must be
restricted to a “care research” trial and never practiced or offered as validated care to
the unsuspecting patient.277

1.8 What are the influences of “placebo effects” in research and

practice outcomes?
What, if any, are the influences of “placebo effects” in research and practice out-
comes? In an erudite exploration from The Lancet, Finniss and colleagues surveyed
the history and practice of placebo effects in medicine.278 Dating back to the Canter-
bury Tales in the late 14th century, Chaucer named the flattering courtier character
Placebo. Placebo controls, false or fake procedures began in the 16th century
designed to discredit exorcisms and then applied to experimentations in medicine
when Ben Franklin’s commission, in 1784 debunked the “invisible natural force”
of animal and vegetable magnetism (mesmerism) after the German doctor Franz
Mesmer.278 Placebo effects became a mainstream medical interest with the wide-
spread acceptance of placebo-controlled RCTs.
Startling to the investigators was the finding that people improved; sometimes
dramatically, in placebo-controlled arms of various studies.
Henry Beecher, MD, of Boston, Massachusetts, in 1955, popularized the idea of
“placebo effects” claiming that about 35% (35.2  2.2%) of patients responded
positively to placebo treatments.279 While Beecher boasted with an inflated impres-
sion of a “powerful placebo,” he failed to distinguish the indisputable placebo
response from other confounding factors.279 Since then, especially in the last 10
years, there is increasing interest in investigating placebo effects by rigorous
research methods. Finniss and colleagues are expansive in their thinking and offer
compelling evidence of complexity regarding the “placebo effect” as they delved
into and dissected the subject noting that evidence has emerged that “placebo ef-
fects” can exist in clinical practice, even if no placebo is given. Yes, a “placebo ef-
fect” can exist even if none is given. To highlight their thinking, they point to a shift
in the emerging mechanistic understanding of “placebo effects” recognizing there is
146 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

not one “placebo effect” but many. Succinctly, there are two overarching mecha-
nisms: psychological and neurobiological with numerous other mechanisms
involved in the “placebo effect.”278 Psychological mechanisms contributing to “pla-
cebo effects” include:
“.expectations, conditioning, learning, memory, motivation, somatic focus,
reward, anxiety reduction and meaning.”278
Multiple studies have shown that clinicians’ beliefs can also affect “placebo ef-
fects.”278 Accordingly, conditioning and expectancy are certainly entangled in the
occurrence of “placebo effects” in clinical practice. The most reasonable interpreta-
tion of the recent literature is that expectancy is first, conditioning follows and is
dependent on the success of the first encounter. That first encounter could be critical
for the development of a subsequent robust placebo response.
“There are also numerous neurobiological mechanisms contributing to ‘placebo
effects’ involving different physiological systems in healthy volunteers and in pa-
tients with a host of different clinical conditions”278
This especially involves neurochemical mediators in the central nervous system.
Research is ongoing.
Blease and colleagues pointed out that recent research has established that “pla-
cebo effects” are authentic psychobiological phenomenon attributable to a total ther-
apeutic context, and the “placebo effect” can be influential in both research and
clinical situations.280 The “placebo effect” blinds many physicians to the reality
that various treatments perceived as beneficial may in fact be merely a “placebo ef-
fect.” Various flawed treatments have been retained merely because of a “placebo
effect.”280
“This was emphasized recently in the study in which patients with irritable bowel
syndrome were assigned to receive either an open-label placebo pill or no treat-
ment. A large proportion of patients may perceive benefit from a placebo, and this
perception may be influenced by patients’ motivation or preconceived expecta-
tions of benefit. These scenarios cloud the thinking and judgment of all concerned
and lead clinicians to reach faulty ‘clinical impressions’. These aforementioned
concerns including ‘placebo effect’ argue for treatment efficacy to be adjudicated
primarily by randomized trials. In some situations, we need to recognize that no
amount of expertise may substitute for data from randomized trials.”280
It is fully understood that without evidence from RCTs, there is no choice but to
rely on clinical reasoning, yet awareness of a possible flawed conclusion because of
a “placebo effects” must always be kept in mind.
Understanding the seriousness of the “placebo question” appraisals defining the
limits of placebos in both medicine and surgery is needed for authority and utility as
both disciplines, medicine and surgery, stress the need for open discussions since as
much unadulterated empirical data as possible are obligatory to make wise clinical
decisions.
 1. Discussion of some specific critical confounding questions 147

1.9 What are the ethics of using placebos in medicine?

The American Medical Association (AMA) has explicit guidelines on clinical use of
placebos and supplies an ethical policy: Placebo Use in Clinical Practice (2007)
advises:
“Physicians may use placebos for diagnosis or treatment only if the patient is
informed and agrees to its use. A placebo may still be effective if the patient knows
it will be used but cannot identify it and does not know the precise timing of its
use. A physician should enlist the patient’s cooperation by explaining that a better
understanding of the medical condition could be achieved by evaluating the ef-
fects of different medications, including the placebo. The physician need neither
identify the placebo nor seek specific consent before its administration. In this
way, the physician respects the patient’s autonomy and fosters a trusting relation-
ship, while the patient may still benefit from the placebo effect.”280

1.10 What are the ethics of using placebos in surgery?

As specified repeatedly, placebo-controlled trials in both surgery and medicine are
each respectively recognized as the “gold standard” way to test the efficacy of a med-
ical therapy or a surgical procedure. Three recent papers, 2016281,282 and 2021283
from the United Kingdom, Germany, and Australia, respectively, tackled the issue
of randomized placebo-controlled surgical trials head on. And one paper from an
ethicist at the NIH discussing the landscape of “sham surgery” approved in research
surgical trials but forbidden in clinical surgical care.284
Writing in the Journal of Medical Ethics, Julian Savulescu from the Faculty of
Philosophy, Oxford Centre for Practical Ethics, Oxford, United Kingdom, along
with doctors Karolina Wartolowska and Andy Carr from the Nuffield Department
of Orthopaedics Rheumatology and Musculoskeletal Sciences University of Oxford,
Oxford, United Kingdom, recognized that “surgical trial is a divisive issue,” yet
argued that just as in medicine, placebo controls for surgery are also necessary to
reduce bias and control for “placebo effects.”281 They presented their defense, justi-
fication, and protocol for surgical trials as these trials are needed to acquire accurate
unbiased data even more so than medical trials as medications can be suspended, but
surgery can lead to useless surgery or irretrievable harm from a specific surgery.
Doubtless, harmful procedures have no place in our ethical practice; therefore, these
authors reason that surgical trials are inescapable to discover and avoid harmful sur-
gical procedures. How to conduct such surgical trials has been considered by the
AMA with a written position on both medical280 and surgical trials.281
The most important document of ethical conduct in medical research is the
Declaration of Helsinki which sanctions placebo-controlled trials in surgery when
there is no proven treatment, and the importance of the study objectives offsets
the risks for the human subjects. The AMA in their effort to provide guidance for
placebo-controlled surgery followed the instruction and conditions of the Declara-
tion of Helsinki highlighting the indispensable informed consent advocating
148 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

standard nonsurgical treatment as a part of randomized placebo-controlled design.

The AMA has adopted these tenants as their policy incorporated into the AMA’s
Code of Medical Ethics.281
From the University of Heidelberg, Germany, Probst et al.282 performed a sys-
tematic review of Central, MEDLINE, and EMBASE researching randomized
placebo-controlled trials, comparing placebo with a surgical procedure.
“The ethical justification for the use of a placebo control remained unclear in two
trials. Placebo-controlled surgical trials are feasible and provide high-quality
data on efficacy of surgical treatments. The surgical placebo entails a consider-
able risk for study participants. Consequently, a placebo should be used only if
justified by the clinical question and by methodological necessity. Based on the
current evidence, a pragmatic proposal for the use of placebo controls in future
randomized controlled surgical trials is made.”282 (Bold italics added)
Nelson and coworkers were interested in raising recruitment rates in placebo-
controlled surgical trials, specifically in orthopedic arthroscopic surgery.283 They
presented four placebo-controlled surgical trials that demonstrated arthroscopic
knee debridement with procedural lavage confirmed no benefit over the “placebo ef-
fect,” which translated into a clinical guideline recommendation against further use
of that arthroscopic surgical procedural lavage. Certainly, a big and important score
for surgical RCTs. Nelson et al. also studied the issue of low recruitment rates in
placebo-controlled surgical trials acknowledging that patients are often unwilling
to accept a surgical procedure knowing the possibility of surgery without benefit.
They listed those patient reluctance issues related to patient confusion, hesitancy,
and unwillingness to participate because of:
“Difficulties understanding concepts such as equipoise, placebo effects, random-
ization, and blinding may also leave many patients confused and unwilling to
participate in a placebo-controlled surgical trial.”283
Equipoise is the term meaning that the assumption is that neither the control nor
experimental group is the “better” intervention and that is the reason for the RCT
design to answer the question in the first place.
The most important influences for improving study enrollment for a surgical
RCT are two specific topics:
1. The question to be answered must be considered important by the patient.
2. There must be a simplified method for providing the patient the important in-
formation and study details before obtaining consent.
One such strategy for improving informed consent and enhancing enrollment
was the use of video animation, while two previous studies have demonstrated
that “educational videos” alone does not improve enrollment. There is some evi-
dence of the positive impact of video animation on enhancing patients’ understand-
ability of the research and fostering an affirmative attitude about participation in the
research. This method of video animation should be explored further.283
 1. Discussion of some specific critical confounding questions 149

1.11 “Sham” surgery, is there an ethical place for research

surgical trials or is it forbidden?
The esteemed and lettered bioethicist Franklin G. Miller, PhD in philosophy from
Columbia University is a senior faculty member at the National Institutes of Health
(NIH), USA, and Professor of Medical Ethics in Medicine (Courtesy) Weill Cornell
Medical College in New York City. Previously, in 2003, writing in the American
Journal of Bioethics Miller presented an ethical analysis of “sham” surgery
(placebo-controlled) in surgical clinical trials.284 Although he mentions other com-
mentators who think “sham” surgery unethical, he argues that:
“.there are no sound ethical reasons for an absolute prohibition of sham surgery
in clinical trials.”
He goes on to make the distinction between clinical medical/surgical research
and clinical medical/surgical care.
“This moral stance, which makes sham surgery appear inherently or presump-
tively unethical, confuses the ethics of clinical research with the ethics of clin-
ical medicine (Horng and Miller 2002; Miller and Brody 2002). The randomized
clinical trial is not a form of personal medical therapy. Rather, it is a scientific
tool for evaluating treatments in groups of research participants, with the ulti-
mate aim of improving medical care. Clinical trials routinely administer inter-
ventions whose risks to patients are not compensated by medical benefits but are
justified by the anticipated value of the scientific knowledge that might be
gained.”284
He cites internal mammary artery ligation for treating angina as a case where two
sham-controlled trials proved that ligation of the internal mammary artery:
“. was no better than a sham operation involving skin incision under local anes-
thesia without ligation of the internal mammary artery (Cobb et al. 1959;
Dimond, Kittle, and Crockett 1960)”.284
“The ethical analysis of the sham control in the arthroscopic surgery trial will
examine six key ethical questions (Horng and Miller 2002):284
1. “Was there scientific and clinical value in conducting this study?
2. Was the use of sham surgery methodologically necessary or desirable to achieve
valid results?
3. Were the risks minimized for those randomized to sham surgery?
4. Were the risks of the sham surgery that were not balanced by the prospect of
medical benefit within a reasonable threshold of acceptable research risk?
5. Were the risks justified by the potential value of the scientific knowledge to be
gained from the research?
6. Did the subjects give informed consent?”
150 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

He cites a number of arthroscopic knee surgery reports for arthritis to present his
ethical examination of a procedural rationale for “sham” surgery with its risk-benefit
calculation along with the associated promise to the patient, with the informed con-
sent covenant.284
Miller concludes with a summation of his thinking regarding the ethics of
“sham” surgery in research trials:
“Sham surgery is not inherently unethical. To criticize this research practice as a
violation of the therapeutic obligation of physicians erroneously conflates the
ethics of clinical research with the ethics of medical care. Nor is sham surgery
necessarily contrary to the requirement of research ethics to minimize risks. In
sum, there are no good reasons for an absolute prohibition of sham surgery in
clinical trials. Ethical judgments should be case specific, depending on the
strength of the methodological rationale for use of sham surgery and the level
of risks posed to subjects.”284 (Bold italics added)
Lately, in 2019, Cotton et al. from the Medical University of South Carolina re-
ported on their designed study of endoscopic treatment of patients with suspected
sphincter of Oddi dysfunction. They were able to develop and effect a system of
blinding in a “sham-controlled” study which they considered a viable and an effec-
tive “blueprint,” a design, for future endoscopy trials. Regarding the issues of
randomization and blinding, they wrote:
“Randomization and blinding are acceptable only if approved by Institutional Re-
view Boards, and applicable only if patients understand and consent.”285
Placebo control in surgical studies is not a capricious call but a vitally important
demand because, “. a review of 53 placebo-controlled surgical studies found that
half of them showed no benefit for surgery over the sham procedure.”285
(Bold italics added). That quotation was from Cotton et al. referencing a 2002 paper
in the Annals of Surgery by Robert Tenery, MD and his colleagues.286
In a most important authoritative paper by the same Robert Tenery, MD and col-
leagues, mentioned above, from the Council on Ethical and Judicial Affairs of the
AMA, following the ethical guidelines in the AMA’s Code of Medical Ethics,
they wrote in the Annals of Surgery the details of how blinding is not only possible
but achievable in surgical evaluation studies. They clearly asserted the reasons for
randomized, double-blind studies in the first place were because this design, the
“gold standard,” reduces the risk of random errors all the while eliminating overall
bias as it diminishes the probability of eventual erroneous deductions and
conclusions.286
“Studies of new operations that contain a surgical placebo control can be single
or double blind (the patient only or the patient and the investigator blind to the
patient’s group). Double-blind studies are preferable and are possible even
though the surgeon will always know what was done in the operating room.
The group of investigators can be blind to the study groups if the surgeon, in
 1. Discussion of some specific critical confounding questions 151

follow-up, closely follows a prepared script with each patient, and if all of the
follow-up measurements are done at an outside institution by investigators other-
wise unconnected to the study. In this way, double-blind investigations can be
achieved in the setting of surgical placebo-controlled studies.”286
This is a vital consideration and an eminently ethically valuable design strategy
because procedures that are ineffective or harmful must be eliminated from all sur-
gical practices, and the most utilitarian study design to avoid ineffective or harmful
procedures is the randomized, double-blind surgical placebo-controlled study. An
important concept forwarded by Tenery et al. is that research is:
“. ethically acceptable only when there is ‘equipoise’, or a belief within the gen-
eral medical community that the experimental intervention will provide at least
equal or greater benefit than the standard therapy.”286

1.12 What are the limitations, if any, to the doctrine of randomized

controlled trials?
As we have repeatedly reported, the powerfully persuasive voice of EBM with the
unimpeachable “gold standard” of RCTs rules the contemporary court of medical
opinion, yet despite its dominance, there are voices of disquiet regarding limitations
and concerns of the RCT especially in surgical design.287 If the design employs mul-
tiple surgeons, of course, technical skill is a patient’s fickle fate for even if the same
“standardized” operative procedure is performed, just as master chefs using the
“identical matching recipe” results can be disturbingly dissimilar, and so the same
fortune for surgeons. Even extrapolation of the results from RCTs may be addition-
ally hazardous for the same reason; not all surgeons enjoy similar technical mastery
or the wisdom to apply that specific “procedure” for the “exact” same “type” of pa-
tient. This harkens back to the observations of Sir Nick Black276 that the evidence
from RCTs is a collection of representative data lacking specificity for that unique
individual patient; therefore, results from the RCT are not widely transferable,
generalizable, as it were, from the trial population to a specific unique surgical pa-
tient; it was for that reason that many surgeons lost interest in the total application of
the RCT. The assumption that results from RCTs are transferable from the study
population to other patients in other situations and that the proposed intervention
to be performed is similar for the “same type” of patient by another surgeon is
open to serious question.
Peter Rothwell from the Department of Clinical Neurology in the Stroke Pre-
vention Research Unit writing a very extensive, complete, and well referenced
article in The Lancet in 2005 also questioning generalizability, asking can the re-
sults of RCTs be rationally applied from a study population to a specific group of
patients in another but “similar” clinical setting?288 He points out that often the
physician’s concern is that poor external validity (generalizability) in that the re-
sults from RCTs has meager application to the specific patient population in
question.
152 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

Quoting Archie L. Cochrane, “Between measurements based on RCTs and

benefit . in the community there is a gulf which has been much under-
estimated”288,289 Rothwell then deliberately declares, referring to RCTs:
“They must be internally valid (i.e., design and conduct must keep to a minimum
the possibility of bias), but to be clinically useful the result must also be relevant
to a definable group of patients in a particular clinical setting; this is generally
termed external validity, applicability, or generalizability. The beneficial effects
of some interventions, such as blood pressure lowering in chronic uncontrolled
hypertension, are generalizable to most patients and settings, but the effects of
other interventions can be very dependent on factors such as the characteristics
of the patient, the method of application of the intervention, and the setting of
treatment. How these factors are taken into account in the design and perfor-
mance of an RCT and in the reporting of the results can have a major effect on
external validity.”288 (Bold italics added)
He continues asking why there is clinician criticism and ubiquitous underuse by
physicians of RCTs:
“Lack of consideration of external validity is the most frequent criticism by cli-
nicians of RCTs, systematic reviews, and guidelines, and is one explanation for
the widespread underuse in routine practice of treatments that were beneficial
in trials and that are recommended in guidelines.”288 (Bold italics added)
This situation is even more troubling for our surgical sisters and brethren.
Another very significant issue according to Rothwell is the reality that:
“.researchers, funding agencies, ethics committees, the pharmaceutical indus-
try, medical journals, and governmental regulators alike all neglect external val-
idity.” (Bold italics added)
External validity refers to generalizability, and generalizability is defined as a
measure of the usefulness of the study results from a broad group of people to spe-
cific clinical situations. If the results of a study are broadly applicable to many
different types of people or situations, then the study is said to have good general-
izability. On the other hand, if an RCT study does not have applicability of their re-
sults to specific patients, then it has poor external validity. Most RCTs have poor
external validity.
Now, despite the limitations of RCTs, Rothwell reassures us about the results of
RCTs with:
“These inevitable limitations do not invalidate the results of RCTs and systematic
reviews, and they are mentioned here partly for the sake of completeness, but the
importance of patient preference, placebo effects, and the doctor-patient relation-
ship outside trials should not be underestimated.”288
 1. Discussion of some specific critical confounding questions 153

Also observing the limits of RCTs, Sir Austin Bradford Hill* commented:
“At its best, a trial shows what can be accomplished with a medicine under care-
ful observation and certain restricted conditions. The same results will not invari-
ably or necessarily be observed when the medicine passes into general use.”290
*“Sir Austin Bradford Hill (1897e1991), is the English epidemiologist and statistician, who pio-
neered the randomized clinical trial and, together with Richard Doll, demonstrated the connection be-
tween cigarette smoking and lung cancer.” Quoted from Wikipedia.

1.13 Is there an ethical approach to surgical and invasive

procedures within randomized controlled trials?
In 2009, Dr. Carol Ashton et al. from Methodist Hospital Research Institute and
Department of Surgery, The Methodist Hospital, Houston, Texas, reflected on the
“double standard” between novel medication approvals and evaluation of innova-
tive surgical procedures. The Food and Drug Administration (FDA) monitors the
development and approval of new drugs before public release by means of RCTs,
while surgical and other invasive procedures have no official regulatory body, and
often hundreds of thousands of procedures are performed before any RCTs are car-
ried out with the claim that trial design and ethical concerns are prohibitive and
limiting.295 Furthermore, she and her colleagues aggressively argue for rigorous ran-
domized trials for surgical and invasive procedures with specific design and report-
ing requirements recommended by her team. Reviewing the negative history of
carotid artery surgery with the idea of “procedure first” and “evidence later” which
for them is ethically repulsive. An important problem in surgical trials is when pa-
tients drop out or cross over during randomization, then the data lose its true authen-
ticity. They propose that it is possible to reconcile medical ethics with rigorous
research methods.291
Writing three years later, the same team from Methodist Hospital Research Insti-
tute and Department of Surgery raised the alarm about the quality and ethics of clin-
ical research of surgical procedures. Their review covered January 1999eDecember
2008 and after an exhaustive literature search of “. 37,944 unique articles across
33 medical subject headings. 2890 trials (7.6%) met our inclusion criteria (Ta-
ble 2).”292 After that monumental review, Wenner et al. concluded that the quality
of surgical trials and the reporting of those surgical trials,
“.is in need of significant improvement.”292 (Bold italics added)
The answer to the question is yes, there is an ethical approach to RCTs for sur-
gical and invasive procedures; however, demands must be met. Wenner and associ-
ates cited five important papers discussing the unique barriers and difficulties related
to surgical clinical trials, but they offered suggestions to vastly improve evidence
from surgical trials including:
154 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

1. Application of CONSORT, which stands for, CONsolidated Standards Of

Reporting Trials, requirements
2. Include a research fellowship into surgical training
3. Improve research education of independent review board members
4. Scientific rigor is possible as 90% of studies reviewed had successful randomi-
zation and only 16% of studies reviewed were blinded; however, to limit bias,
blinding of the independent outcome assessors is possible
5. Regarding ethics: “Clinical research ethics require that the risks of harm to
participants be outweighed by the value of the knowledge to be generated.”
Finally, there are ethical imperatives because when surgical and invasive proced-
ure trials are poorly constructed, absent bias reduction, and are inadequately con-
ducted, then these trial results are of “questionable scientific value.”292
We ask, when results from such trials that lack proof of efficacy or safety are
applied to unsuspecting clinical patients, who is accountable?

1.14 What are the obligations and accountability to our patients

regarding surgical innovations?
Yes, as physicians and surgeons, medicine, have the exquisite moral obligation to be
accountable to the highest methodical standards, with essential ethical behavior
especially as surgeons exploring surgical innovations. In a marvelous three-part se-
ries all published in The Lancet, in the September 26, 2009 issue, the entire topic of
surgical innovation is intensely reviewed. Surgical innovation can result from
evidence-based principles and not “trial and error” so as to avoid “innovations”
that are ultimately deemed useless or harmful to patients.
The paradigm of critical appraisal arises before wide-spread adoption proceeds
from innovation, development, exploration, assessment, long-term implementation,
and monitoring. Essentially, ethical surgical innovation is “staged development”
with unremitting ever continuous and endless evaluation.
Jeffrey Barkun and colleagues293 discuss evaluation and the various stages of
surgical innovations, Patrick Ergina et al.294 cover the variety of challenges related
to evaluating surgical innovation and RCTs, while Peter McCulloch and his associ-
ates295 in their thoughtful discussion preferred the extensive use of “prospective da-
tabases and registries.” Favoring, of course, RCTs with prospective design planning,
pretrial statistical analysis with power calculations, and measures accounting for
learning curves and other variables with rigorous results analysis including
recording and reporting of late outcomes and complications. McCulloch et al.
continued to emphasize ethics and safety over mercantile profits and cautioned
that restrictive regulation must never negate imaginative creativity.295
 1. Discussion of some specific critical confounding questions 155

1.15 What are the CONSORT requirements and what’s their

importance for researchers and journals?
McCulloch et al.295 were certain that improvements in research reporting by inves-
tigators and acceptance by the journal editors would occur only after high standards
are attained such as those of CONSORT. Having a uniform method of reporting
RCTs would markedly improve trial methodological construction thereby avoiding
publishing of flawed studies.295 Thirteen years earlier, in 1996, Douglas Altman
writing in The British Medical Journal recognized the critical importance of a
well-executed RCT, which explicitly informs the readers as to precise methodology
of the reported RCT.296 That is, the purpose of the CONSORT statement which is a
standard way for all interested parties, researchers, journal editors, and physicians of
the general readership to know exactly how the RCT was performed, with a stan-
dardized check list for the authors of trials to adhere to and for journal editors to de-
mand before the results of RCTs are published and disseminated.296,297 In fact, The
Journal of the American Medical Association (JAMA), The British Medical Journal,
The Lancet, and The Laryngoscope all support the CONSORT check list with the
hope that the research trialists will follow the checklist to improve RCTs reporting
and now considered the correct conduct for future research.296
As recently as 2015, Peters et al.213 used the CONSORT statement, which was
developed to promote consistency, clarity, accuracy, and transparency of reporting
of RCTs, reviewed and compared the five top general medical and ENT journals
(by impact factor), assessing the number of CONSORT items adequately reported.
They found that the reporting quality in the ENT journals was “suboptimal,” while
the reporting of RCTs in the medical journals was of higher quality. (Bold italics
added) They also suggested that the journal editors endorse using the CONSORT
statement to improve reporting of the results from RCTs.213
As pointed out by Agha et al.,269 the CONSORT statement which was first pub-
lished in 1996 by Begg et al.297 and revised in 2001 by Moher and colleagues298 was
intended to improve the overall value of RCTs by insisting on design and reporting
standards through a specific checklist of 22 essential items and flow diagram that has
the obligatory requirement of being included in the reporting of every RCT to each
journal for consideration for publication.
More recently, in 2010, the checklist and flow diagram have been updated yet
again and expanded to 25 essential items by the leading authorities Douglas Altman,
David Moher, Kenneth Schulz, and others299,300 with the details located at: www.
consort-statement.org
156 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

Agha et al. commenting on the necessity for the CONSORT requirements in

research, especially the reporting of RCTs in surgery was:
“There is a clear need to ensure that medical research, especially relating to clin-
ical interventions, is carried out and reported to the highest possible
standards.”296
 1. Discussion of some specific critical confounding questions 157

Douglas Altman (1948e2018) said it so succinctly and beautifully:

“To maximize the benefit to society, you need to not just do research, but do it
well.”
So, these CONSORT requirements are important for clinical investigators to
have an accurate repeatable standard guideline to follow for performing valid
RCTs of the highest quality, so ultimately practicing physicians and surgeons
have proven principles to follow for effective clinical patient care.
Journal editors and peer reviewers should also demand that those investiga-
tors using RCTs follow the CONSORT requirements, so that the highest
quality studies are transparently performed with the most accurate data published
for their readership to consider when making clinical decisions. Even after a
quarter of century of demand for following the CONSORT statement,
many RCTs still do not adhere to those principles in their papers published
in the ENT literature. Just a few years ago in 2018, the group from McGill
University evaluating RCTs in otolaryngology and adherence to the CONSORT
statement concluded that the reporting of RCTs in top nine ORL-HNS
journals and in the top Canadian ORL-HNS journal is “suboptimal.”301
(Bold italics added)

1.16 What is propensity score matching all about?

Propensity score systems can be used in observational studies to decrease a con-
founding variable; an indication of bias. This technique is called propensity score
matching (PSM). The PSM reputation has increased in the medical literature
because improper methodology may lead to biased treatment effects or limited sci-
entific reproducibility.
Prasad et al. aimed to study the quality of PSM methodology reported in the ENT
literature.302
“Such analyses are able to measure and balance predetermined covariates be-
tween treated and untreated groups, leading to results that can approximate those
generated by randomized prospective studies when such trials are not
feasible.”302
Since RCTs in the ENT literature is under 4%205,207 because they are difficult,
regularly expensive, and at times ethically challenging to perform, observational
studies are utilized more frequently with a retrospective investigation to make con-
nections concerning treatment effectiveness, which then can be followed by confir-
matory studies. Regrettably, these observational studies are vulnerable to “treatment
selection bias” owing to their lack of randomization; however, their results may
become routine clinical practice without the same scientific scrupulousness as an
RCT.
158 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

“In an attempt to improve comparisons between cohorts in observational studies,

statistical methodologies have been developed in order to reduce confounding
when randomization is not possible. The most commonly employed statistical
technique to reduce bias is multivariable regression.”302 (Bold italics added)
A confounding variable is an “extra” variable not accounted for that can ruin an
experiment giving flawed results. For example, suggesting a correlation when in fact
there isn’t one or even unwittingly introducing bias is a confounding variable. That’s
why it’s important to know confounding factors and how to avoid getting those fac-
tors into a research experimental design in the first place.
Prasad el al. provided pivotal recommendations to future authors regarding
reporting of PSM at the same time they critically concluded that although PSM
has increased in frequency in the ENT literature, the quality of those reports can
be “improved.”302 (Bold italics added)
In a competent comparison study writing from Paris, France, in the Annals of
Surgery, Lonjon et al., in a metaepidemiological study, compared the treatment ef-
fect from prospective nonrandomized studies (NRSs) with PSM analysis and RCTs
of surgical procedures and found that:
“There was no statistically significant difference in treatment effect between NRSs
with PS(M) analysis and RCTs. Prospective NRSs with suitable and careful
PS(M) analysis can be relied upon as evidence when RCTs are not possible.”303
In other words, if performed accurately, analysis of outcome differences between
treated and untreated participants following PSM can imitate an RCT.303,304 Note:
the (M) is added to the quotation and for clarity, stands for the word “matching.”

1.17 What about using clinical practice guidelines and associated

conflicts of interest?
It is well recognized that comprehensive clinical practice guidelines (CPGs) can pro-
vide significant information to busy “overworked” physicians and surgeons seeking
advice regarding diagnosis and treatment of an assorted mix of medical and surgical
disorders. The primary motivation for these recommendations offered by CPGs is
for the enhanced improvement of patient care based on the “best available solid ev-
idence” usually from RCTs. Developing even one CPG requires authoritative judg-
ments from various individuals, thereby potentially introducing bias. At times,
members of a guideline development team lack solid evidence requiring dependence
on individual “expert” interpretations positioning some members into a COI. The
legions of healthcare providers including physicians and surgeons as well as the pub-
lic all depend upon the integrity, honesty, and transparency of all those individual
members involved in creating CPGs. It’s all about the belief in the expectation
and conviction, in the confident certainty of trust.
According to Sniderman et al.180 when and if the data from RCTs are limited,
incomplete, inconclusive, conflicting, or starkly nonexistent, then contemporary
 1. Discussion of some specific critical confounding questions 159

CPGs or advisories are often still relied upon for a reliable and trusted expert
opinion.180
Loss and Nagel writing from Germany favored evidence-based guidelines which
were supportive of free decision-making, yet were cautious about the confining in-
fluence of evidence-based clinical guidelines in surgery fearing the restrictive influ-
ence on independent thinking which “.may lead to an oversimplified and rigid
standardization in medical care (‘cook book medicine’). In addition, scientific prog-
ress might be prevented by inflexible guidelines.”305 (Bold italics added)
Dr. Bruce Barrett at the University of Wisconsin, Madison writing in The Journal
of General Internal Medicine in 2012, continues the discussion by supporting the
notion that medical decision-making is really an individualized process between
physician and patient, and because decisions are between doctor and patient that pa-
tient guidelines are beyond the rigidity and inflexibility that Loss and Nagel spoke
of, but that guidelines are irrational.
“.and because the ethical principle of autonomy mandates informed choice by
patient, medical decision-making is inherently an individualized process. It fol-
lows that the practice of aiming for universal implementation of standardized
guidelines is irrational and unethical. Irrational because the possibility of bene-
fits is implicitly valued more than the possibility of comparable harms, and uneth-
ical because guidelines remove decision making from the patient and give it
instead to a physician, committee or health care system. This essay considers
the cases of cancer screening and diabetes management, where guidelines often
advocate universal implementation, without regard to informed choice and indi-
vidual decision-making.”306
Woolf and colleagues from the Department of Family Practice, Virginia
Commonwealth University, Fairfax, Virginia noted the assured benefits of clinical
guidelines as improving outcomes, reducing morbidity and mortality while
enhancing the quality of life and consistency of medical care for patients regardless
where they are treated or by whom.307 All positive. Guidelines that are based on sci-
entific evidence (evidence-based guidelines) simplify which interventions are
proven to be of benefit with substantiating supporting data. All good. Now Woolf
et al. also discussed the limitations with the most important limitation of the guide-
line recommendation is that it might be wrong. Wrong because the scientific evi-
dence maybe flawed, ineffective, or even harmful, and with the promotion of
flawed guidelines, the greatest danger is to the patients. What is helpful and best
for patients “globally” as recommended by the guidelines may be inflexible and
inappropriate for a specific individual patient. Flawed guidelines harm not only
the patient but also the physicians and surgeons practicing from fallacious science.
Clinical guidelines are not the ultimate panacea but only an option to consider,
especially when a clinical care dilemma needs clarity, then a set of guidelines based
on accurate unbiased solid scientific evidence (evidence-based guidelines), then
those guidelines make sense to consider for our patients.307
160 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

David Jevsevar and Kevin Bozic in the Department of Orthopedics at Dartmouth-

Hitchcock Medical Center, Lebanon, New Hampshire, in the context of decision-
making, defined CPGs as:
“.a systematic approach to exploring, evaluating, appraising, and synthesizing
the literature so that the individual reader need not perform each of these time-
consuming activities.”308
The Institute of Medicine (IOM) defines a CPG as a “systematically developed
statement to assist practitioner and patient decisions about appropriate healthcare
for specific clinical circumstances.”308 Wisely, because of the well-known quality
variability of any specific CPG, the Orthopedic Academy suggests grading the au-
thority and strength of any CPGs as: strong, moderate, limited, and consensus.
That a CPG should be considered no more than a well-thought-out reference tool,
ultimately serving for proficient patient care, integrating physician expertise with
a unique patient’s situation and preferences.308
In a very interesting facet of CPG Stefan Timmermans from the Department of
Sociology, University of California-Los Angeles traces the evolution and impact of
CPGs, on clinicians by addressing ambiguities of patient care with a set of standard-
ized CPGs and yet recognizing the commanding power transfer from physician au-
tonomy to physician accountability.309 Timmermans like Loss and Nagel305 was
concerned about rigidly constructed CPGs that may inflexibly stipulate how medical
care should be accomplished, threatening professional freedom, our sovereignty.309
In reality, studies have shown that there is only “modest” physician behavior change
regarding rigidly following CPG directives, but this “nonobedience” to CPGs may
mark the physician susceptible to third-party “oversight” and eyes from legal circles
with all that entails.309
As has been noted, CPGs are costly to create, and most recently, CPGs have been
seriously discussed by various participants and stakeholders including physicians,
surgeons, third-party payers, legal experts as a means of measuring performance,
ranging from reimbursement to malpractice litigation. With the trustworthiness of
the CPGs creators, the authors of any given group of CPGs need to have impeccable
credentials for integrity, free from any fragrance of fiscal COIs. The University of
Michigan otolaryngologist, Gordon Sun, MD, a Robert Wood Johnson Foundation
Clinical Scholar, extolling the American Academy of OtolaryngologyeHead and
Neck Surgery Foundation wrote in 2013 that:310
“Since 2004, the 9 CPGs sponsored by the American Academy of Otolaryngology-
Head and Neck Surgery Foundation have been developed with full disclosure and
appropriate management of potential pecuniary conflicts of interest. This commen-
tary discusses the potential for conflict of interest in otolaryngology CPGs and how
the otolaryngology guideline development process can serve as a model for other
professional medical organizations.”310 (Bold italics added)
Firestorm! Flash! Five years later, in 2018, three medical students and a PhD
clinician from the Department of Psychiatry Oklahoma State University Center
 1. Discussion of some specific critical confounding questions 161

for Health Sciences, Tulsa, Oklahoma, using both the Open Payments database and
the Dollars for Docs website, which identifies industry payments to physicians,
investigated the relationship between physicians developing CPGs and industry.
This faction of four exploded the myth of candid and reliable integrity in their
COI statements in the development of CPGs by guideline development groups
(GDGs) of the American Academy of OtolaryngologyeHead and Neck Surgery
(AAO-HNS).311 (Bold italics added)
The findings of Horn et al.311 are so striking and arresting; to avoid any sugges-
tion of misrepresentation, we quote entirely from both their Key Points and Abstract:

1.17.1 “Key Points

1.17.1.1 Question
What is the extent of potential financial conflicts of interest among physicians who
author otolaryngology clinical practice guidelines?

1.17.1.2 Findings
In this cross-sectional analysis of 49 authors of otolaryngology clinical practice
guidelines, 39 received industry payments and three did not accurately disclose
financial relationships. Of the three Institute of Medicine standards assessed,
only one was being enforced. (Bold Italics added for emphasis)

1.17.1.3 Meaning
Guideline authors received significant industry payments, and most panel members
received payments from industry, which raises concern about potential financial con-
flicts of interest in the otolaryngology guideline development process”

1.17.2 Abstract
Importance: Financial relationships between physicians and industry have influ-
ence on patient care. Therefore, organizations producing clinical practice guidelines
(CPGs) must have policies limiting financial conflicts during guideline development.
Objectives: To evaluate payments received by physician authors of otolaryn-
gology CPGs, compare disclosure statements for accuracy and investigate the extent
to which the American Academy of OtolaryngologyeHead and Neck Surgery com-
plied with standards for guideline development from the IOM.
Design, setting, and participants: This cross-sectional analysis retrieved CPGs
from the American Academy of OtolaryngologyeHead and Neck Surgery Founda-
tion that were published or revised from January 1, 2013, through December 31,
2015, by 49 authors. Data were retrieved from December 1, 2016 through December
31, 2016. Industry payments received by authors were extracted using the Centers
for Medicare & Medicaid Services Open Payments database. The values and types
of these payments were then evaluated and used to determine whether self-reported
disclosure statements were accurate and whether guidelines adhered to applicable
IOM standards.
162 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

Main outcomes and measures: The monetary amounts and types of payments
received by physicians who author otolaryngology guidelines and the accuracy of
disclosure statements.
Results: Of the 49 physicians in this sample, 39 (80%) received an industry pay-
ment. Twenty-one authors (43%) accepted more than $1000; 12 (24%) more than
$10 000; 7 (14%) more than $50 000; and 2 (4%) more than $100 000. Mean
(SD) financial payments amounted to $18 431 ($53 459) per physician. Total reim-
bursement for all authors was $995 282. Disclosure statements disagreed with the
Open Payments database for three authors, amounting to approximately $20 000
among them. Of the three IOM standards assessed, only one was consistently
enforced.
Conclusions and relevance: Some CPG authors failed to fully disclose all
financial conflicts of interest, and most guideline development panels and chairper-
sons had conflicts. In addition, adherence to IOM standards for guideline develop-
ment was lacking. This study is relevant to CPG panels authoring recommendations,
physicians implementing CPGs to guide patient care, and the organizations estab-
lishing policies for guideline development.”311 (Bold italics added)
David Tunkel in the Department of OtolaryngologyeHead and Neck Surgery,
Johns Hopkins University School of Medicine, Baltimore, Maryland writing in
JAMA Otolaryngology Head Neck Surgery commented on trustworthiness of
CPGs and COI of those involved in creating those recommendations after reading
Horn et al.311 He said:
“Clinical practice guidelines must be trustworthy, and the Institute of Medicine
(IOM) and the Guideline International Network have provided standards for
CPGs.1 A major threat to the creation of trustworthy guidelines is conflict of in-
terest (COI) among the organizations and the committee members who create
CPGs.”312
Dr. Tunkel adroitly observed that COIs may be threefold: (1) Financial, (2) In-
tellectual, i.e., by holding exclusive and specific views precluding dispassionate
objective judgment, and (3) Professional COI where the guideline developer has a
clinical practice affected directly by guideline proposals. Tunkel was similarly trou-
bled by the fact that:
“.several AAO-HNS guideline authors received large payments from companies
related to their guideline topic and even more troubling that disclosure of conflicts
for a few was not accurate.”312
David E. Tunkel’s comment that several guideline authors’ disclosure of COIs
“were not accurate” is undeniably troubling.312 The honor system runs amuck;
obsessed with mammon and with cynical ruefulness, the letters “CPG” might
now stand for clinician payment guidelines (CPGs), especially for those colleagues
who accepted funding and otherwise without the integrity of direct disclosure of
their conflict(s) of interest.
 1. Discussion of some specific critical confounding questions 163

Some “good” news arrived from the Yale University group with the work of
Pathak et al.313 who found that: “Otolaryngologists continue to demonstrate limited
industry ties when compared with other surgical specialists.” Once again, a year
later the Yale group from the Division of Otolaryngology, Yale University School
of Medicine, New Haven, Connecticut, comparing drug and device industry year
to year payments “opened our eyes” about those disbursements to otolaryngologists
with a final flourish from their 2019 paper:
“Conclusion: Industry payments to otolaryngologists decreased to $11.2 million
in 2017 from $14.5 million in 2016. Much of the decrease can be attributed to de-
creases in consulting fees and ownership payments. It is important that otolaryn-
gologists remain aware of changes in industry funding with each release of the
Open Payments Database.”314
Very recently, in April 2021, a powerful paper from the Department of Medicine,
Center for Biomedical Ethics, and the Law School, at Vanderbilt University, Nash-
ville, Tennessee, J. Henry Brems and colleagues skillfully and punctiliously studied
the COI public policies statements among 46 organizations producing five or more
CPGs since the IOM, now the National Academy of Medicine, publicized their COI
policies 10 years ago in 2011.315
These 46 organizations were identified by CPG databases, and their COI policies
were acquired after a public internet search. Among the 46 organizations that trum-
peted five or more CPGs, 36 (78%) had a COI policy but only two of the 36 (6%) met
the divestment requirement for a financial COI. Cheerfully, the disclosure require-
ment of a COI had the highest frequency of compliance with 33 of 36 (92%) orga-
nizations with a COI policy disclosed a COI. Nevertheless, the Vanderbilt team
concluded that:
“Among organizations producing CPGs, COI policies frequently do not meet
IOM standards, and organizations often violate their own policies. These short-
comings may undermine the public trust in and thus the utility of CPGs. CPG-
producing organizations should improve their COI policies and their strategies
to manage COI to increase the trustworthiness of CPGs.”315
Dr. J.C. Denneny 3rd from the American Academy of OtolaryngologyeHead
and Neck Surgery Foundation, Alexandria, Virginia, writing from his pivotal post
as Executive Vice President/CEO of the American Academy of Otolaryngologyd
Head and Neck Surgery and its Foundation representing about 12,000
otorhinolaryngologistsdhead and neck surgeons in the United States, explaining
the CPG development process at the academy while tackling the COI situation by
Horn et al.311 who were critical of the practices at the academy by some who failed
to honor their commitments to their integrity regarding COI. Denneny et al. referring
to the academy’s CPG development process postulated that:
“By focusing only on conflict of interest and related potential bias, the authors
(Horn et al.311) do a disservice to the process as a whole.”316
164 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

Dr. Denneny and coauthors316 submitted that COIs cannot be totally circum-
vented or entirely prevented, so their answer is “proper management,” which in-
cludes total transparency and the responsibility of the chair and the members of
the GDG to recuse themselves from discussions, voting or even removal from the
entire group process should conflicts arise. The authors also pointed out that:
“Questions regarding the accuracy of the Open Payments Database (OPD)* have
been reported, with a 2014 estimate suggesting that about 30% of data collected
may be inaccurate. 10,11. References 10 and 11 listed by Denneny et al. are:
(Bold Italics added)

10. Maddux D. Open payments: CMS data makes headlines. Acumen Physician
Solutions website.https://acumenmd.com/blog/open-payments-cms-data-
makes-headlines/. Published October 6, 2014. Accessed January 16, 2018.
11. Babu MA, Heary RF, Nahed BV. Does the open payments database provide
sunshine on neurosurgery? Neurosurgery. 2016;79:933e938.
*Note: Reference 10. Above: The article by Dugan Maddux, MD Vice President, Kidney Disease Ini-
tiatives written October 6, 2014 thought that the data did not specify enough information to make intel-
ligent comments about industry and physician relationships plus data could be misleading and there were
“significant concerns about inaccurate data.” Reference 11. Above: “The Open Payments Database
(OPD) was launched by the Centers for Medicare & Medicaid Services in 2014. Through this online
searchable database, the public can explore physician-industry interactions.” Babu et al. concluded:
The OPD details physician interactions with industry and has multiple inaccuracies.
The simplest way to answer the matter is for the officials at the American Acad-
emy of OtolaryngologyeHead and Neck Surgery to unequivocally ask the involved
individuals about the accuracy of the allegations, emphasizing that COI can be three-
fold: (1) Financial, (2) Intellectual, and (3) Professional, as pointed out by David
Tunkel.312
Digesting these revelations amid allegations of inaccurate data and multiple
inaccuracies, from the Open Payments database and the Dollars for Docs website
we think as a profession, there is much to contemplate, ruminate, and ponder, prior
to ultimate action, since the underpinning of medical care is all about, as previously
stated, the expectation and conviction, in the confident certainty by colleagues and
the general public of trust in our unmitigated total integrity; integrity matters.
Lastly, this section is closed with a fascinating and intriguing corollary paper
regarding the use of CPGs written by Dr. Chris Taylor, in 2014, a neurosurgeon
and Vice Chairman of the Department of Neurosurgery at the University of New
Mexico School of Medicine contributing to the Journal of Legal Medicine about us-
ing CPGs in determining the standard of care in the medicolegal sense.317 He
reviewed a number of legal cases determining that since CPGs are numerous and
variable in quality, with some CPGs established on evidence-based RCTs and meta-
analyses and others based purely on the “consensus opinions” of “experts” who
have, none the less, reviewed the scientific basis of their opinions, regarding a
 1. Discussion of some specific critical confounding questions 165

specific clinical situation but without the rock-solid evidence of RCTs. The entire
concept of “evidence-based-medicine” is the distinction between decisions based
on hard scientific evidence, RCTs as opposed to decisions based on expert opinion.
Certainly, our legal system allows for CPGs to be presented to judge and jury by
expert medical witnesses representing both sides of a litigation for bolstering their
position. While there are some CPGs that approximate the “standard of care” in
the medicolegal definition but considered alone, CPGs do not equate or legally
represent the “standard of care” in a court of law.317

1.18 What about practice replacement, reversal, and the nature of

medical progress?
Ever since Hippocrates, the gravitational principled core of medicine which main-
tains moral authority is: the interest of the patient is the only interest of concern.
With the enormity of that gravitational moral and ethical pull, physicians and sur-
geons are obligated to continuously scrutinize, evaluate, and reevaluate their current
practices ever searching for improvements, for optimal patient care procedures and
techniques. As a profession, we are ever wary of practices that are useless or harmful
searching for validated therapies to safeguard and protect the best interests of our
trusting patients. Unvalidated therapies need scrutiny with attempts at verification
to be embraced and approved as sensible and successful or discarded as useless or
harmful.
Viny Prasad and Adam Cifu writing in the Yale Journal of Biology and Medicine
cited the twofold reasons that medical therapies decline in esteem and are no longer
used: (1). Replacement or (2). Reversal
1. Replacement occurs when a practice is displaced by one that is better.
2. Reversal (discontinued) occurs when a practice is discontinued not by being
exceeded and replaced by something better, but when it is realized that the
practice was never really successful or it was discovered to be harmful, it is then
reversed.318
Reversal produces a loss of trust for the entire medical system by both patients
and physicians. The solution to a reversal is finding the answer by randomized
controlled trials (RCTs) for newer effective practices or RCTs can be used to reeval-
uate practices currently in existence.318 RCTs avoid bias and are absolutely indis-
pensable for intelligently comparing competing medical practices.214 By
comparison, replacement represents a coherent and logical progression in medical
care, while reversal exposes errors which by its very nature damages trust.
Prasad and Cifu cite examples including Atenolol that “.is no better than pla-
cebo in increasing survival.”318 Some other examples offered included Class 1C an-
tiarrhythmics, vertebroplasty, mammographic screening does not benefit women in
their 40s, hormone replacement therapy for treating menopausal symptoms, and
others.318 A common sense understanding of science or that a treatment objective
“makes sense” does not assure investigational experimental confirmation, proof.
166 CHAPTER 8 “Best Reduction Method” for “hypertrophy” reduction

Proof is obtained though good evidence, and good evidence is obtained through
well-conceived and well-done RCTs.
“Well-done means a strong methodology, adequate power, and blinding, such tri-
als are appropriately controlled (in certain cases, sham-controlled) and address
proper endpoints.”318 This applies not only to medical and surgical procedures
but to new technologies too “.since we continue to adopt new technologies
not because they are supported by the strongest evidence base, but based on a
common sense appeal that they should work.”318
These authors cited a recent article announcing that only 27% of new and novel
cardiac devices had randomized testing prior to the United States FDA approval.
Straightforward testing would be a blessing to both patients and physicians alike.
Reversal reminds us all that failure to do the straightforward testing, exposes patients
to possible profound and permanent damage.318 Preferably, questionable medical
practices are replaced by better ones, based on strong and substantial comparative
trials RCTs where new practices overtake older ones inaugurating novel canons
and new standards of care.319 As previously presented, Vinay Prasad and associates
reviewed over 2000 new articles with over 1000 covering medical practice. Over 900
articles tested new practices, while 363 articles tested established standard of care
practices, 146 (40.2%) of 363 reversed (discontinued) the established standard of
care practice, whereas 138 (38.0%) of 363 reaffirmed and 79 were inconclusive
regarding the established standard of care practice.
“The reversal of established medical practice is common and occurs across all
classes of medical practice.” “Reversals included medications, procedures, diag-
nostic tests, screening tests, and even monitoring and treatment guiding devices.
We were unable to identify any class of medical practice that did not have some
reversal of standard of.”271(Bold Italics added)
A comment, of the 981 articles testing new practices, 77% were replacements
(improvements-betterment) and 17% no better or worse, so back to the “drawing
board” and 6% were inconclusive.271
Following Prasad et al. with the demands that all, or almost all, practices, tech-
niques, and devices be studied in well-designed trials (RCTs) to solve clinical prob-
lems with dictum, “evidence first.”271 In that way, medicine advances, progressing
toward a loftier perch with safer and more predicable positive outcomes for patients.
Surgeons began noticing that data from many scientific studies including RCTs were
not widely or easily assignable to a given unique individual surgical patient leading
to the receding enthusiasm among surgical constituents for RCTs and its
generalizability.
In a dazzlingly provocative paper published in 2016, John Ioannidis from the De-
partments of Medicine, Health Research and Policy, and Statistics, and Meta-
Research Innovation Center at Stanford (METRICS), Stanford University, Palo
Alto, California, defended his assertion that most clinical research is not useful
by arguing that for clinical research to be useful, it must have unbiased transparent
 1. Discussion of some specific critical confounding questions 167

pragmatic utility for a patient’s well-being. After listing a number of “utility fea-
tures” (Table 8.1 below) that must be met for clinical research to be useful, he
concluded by announcing that:
“Overall, not only are most research findings false, but, furthermore, most of the
true findings are not useful. Medical interventions should and can result in huge
human benefit. It makes no sense to perform clinical research without ensuring
clinical utility. Reform and improvement are overdue.”320
In closing this section, we read from the perspicacious philosophical pen of Ser-
gio Cocchei, University of Bologna School of Medicine, Bologna, Italy, writing in
2017 about error and contradictions in medicine proposing that the occurrence of
adverse events is not totally damaging since, quoting the 17th century words of
Sir Francis Bacon, “truth emerges more readily from error than from confusion.”
Cocchei paraphrasing the work of the late Professor Sir Karl R. Popper, the 20th
century Austrian philosopher of science, from his 1959 book “The Logic of Scien-
tific Discovery,” who:
“introduced the concept of an ‘approximate temporary truth’ that constitutes the
engine of scientific progress.”321 (Bold italics added)
Cocchei further invites us to consider the temporal quality of “truth” since
biomedical research and clinical practice have witnessed many, as Prasad et al.271
has revealed, reversals and rejections of once dearly held beliefs. Medicine utilizes
the “best information available” at the time, allowing for “educated guesses,” which,
of course, is subject to change. That we physicians and surgeons should tolerate “un-
certainty” acknowledging the reality that medical theories and practices are subject
to dislocation, disruption, continuous change, and improvements since that’s the na-
ture of medical progress.321

Table 8.1 Features to consider in appraising whether clinical research is

useful.
Feature Questions to ask

Problem base Is there a health problem that is big/important enough to fix?

Context Has prior evidence been systematically assessed to inform (the need
placement for) new studies?
Information gain Is the proposed study large and long enough to be sufficiently
informative?
Pragmatism Does the research reflect real life? If it deviates, does this matter?
Patient Does the research reflect top patient priorities?
centeredness
Value for money Is the research worth the money?
Feasibility Can this research be done?
Transparency Are methods, data, and analyses verifiable and unbiased?
Table 8.1 from: Ioannidis JP. Why most clinical research is not useful. PLoS Med. 2016;13(6):
e1002049. https://doi.org/10.1371/journal.pmed.1002049. PMID: 27328301; PMCID:
PMC4915619.320
 CHAPTER

Children and inferior

turbinate reduction
9
Principally, this book is about the Empty Nose Syndrome and Inferior Turbinate
Management in Adults and not about the pediatric population with enlarged inferior
turbinates. However, because of the enormity of a possible lifespan of the surgical
consequences in children, we think some cosmic frame of reference is vital to the
childhood turbinate debate; therefore, a very succinct overview concerning children
and inferior turbinate reduction is warranted; we are speaking about our children and
a possible lifetime handicap!
When compared to adults, turbinate reduction surgery in children is beyond
debatable, it’s contentious. Anxiety centers around complications such as excessive
bleeding, mucosal damage with synechia, possible alterations of future facial devel-
opmental growth plus long-term disruption of nasal physiologic function.
Numerous papers have been published in the medical literature touting one
method or another for turbinate reduction in children from the “maximist” hair-
raising terrifying total turbinectomy to a “minimalist” out-fracture (lateralization)
of the inferior turbinate with submucous inferior turbinoplasty with or without ton-
sillectomy and adenoidectomy.
Often these procedures are associated with a totally truncated follow-up of less
than five years, sometimes merely months. In 2010, Leong and colleagues contrib-
uted to the International Journal of Pediatric Otorhinolaryngology knowing full
well that the subject of surgical management of turbinates in children was still
patently prickly and considerably controversial. Their stated goal was: “To evaluate
the ‘evidence’ for inferior turbinate surgery in children suffering with chronic nasal
congestion.” After their extensive literature search, only 11 selected studies fulfilled
their inclusion criteria with ages ranging from one-year-old to 17 years of age and
follow-up from a paltry 3 months to a substantial 14 years after surgery. With
(n ¼ 730) patients, 79.1% had turbinate surgery exclusively, as a “standalone pro-
cedure,” while the other 21.9% had other procedures with an additional adenotonsil-
lectomy, performed most frequently. Unfortunately, the outcome measures varied so
significantly between studies that cross-study comparisons were impossible. Howev-
er, after serious study and rightful reflection regarding turbinate surgery in children,
Leong, Kubba, and White concluded:
“There is currently little evidence to support turbinate reduction surgery in
children. The role of surgery, if any, has not been properly examined. Further-
more, the long-term effects on nasal airflow dynamics, nasal physiology, and
long-term complications remain to be studied.”322 (Bold italics added)
Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00009-3 169
Copyright © 2024 Elsevier Inc. All rights reserved.
170 CHAPTER 9 Children and inferior turbinate reduction

Just a few years ago, in 2019, nine years after Leong et al.322, a group from the
Department of Otolaryngology-Head and Neck Surgery, Boston University, School
of Medicine, and the Department of Surgery, Veterans Administration Medical Cen-
ter, Boston, Massachusetts, stated their desire to compare the “efficacy, duration,
and complications” while charting the evolution of different pediatric surgical
methods (turbinectomy, electrocautery, lasers, submucous microdebridement, and
radiofrequency) for managing pediatric inferior turbinate hypertrophy. We chose
to report this paper because of the number (n ¼ 1,012) of children involved. After
a comprehensive literature review, they noted that pediatric surgeons are now
thinking past “conservative” medical options in pursuit of surgical management.
These authors acknowledge that surgery in children is an “escalation” in the man-
agement of inferior turbinate “hypertrophy.” On the other hand, being ethically
honest, these authors also acknowledged that in 2019:
“Still, no guidelines currently exist to help guide the escalation of management
in children.”323 (Bold italics added)
Yet, they pushed forward, justified by the gathering assembly of “medical fail-
ures” when 16 reviews (1989e2019) fulfilled their inclusion criteria (n ¼ 1,012)
children ranging from 1 to 17 years of age. Their study’s procedural characteristics
and outcomes are summarized in Tables 9.1 and 9.2 below.
It is clearly seen, Table 9.2, that the radiofrequency volumetric tissue reduction
(RVTR) method has a short-lived follow-up from 6 weeks to 12 months. Komshian
et al. drew support from their reference number 36. Bhattacharyya and Kepnes tout-
ing the advantages of coblation in adults with long-lasting reduction in nasal vol-
ume, subjective nasal airway improvement, and low complication rates all
credited to mucosal preservation. RVTR steadily gained acceptance as a low-risk
method in children as well, supported by reference number 36. Bhattacharyya N,
Kepnes LJ. Clinical effectiveness of coblation inferior turbinate reduction. Otolar-
yngol Head Neck Surg. 2003;129(4):365e71. https://doi.org/10.1016/s0194-
5998(0300634-x). PMID: 14574290.
Bhattacharyya and Kepnes simply had a modest (n ¼ 24) patients with follow-up
evaluations at 3 and 6 months. Nonetheless, they boldly and confidently concluded
that:
“Coblation inferior turbinate reduction is an effective procedure for inferior
turbinate hypertrophy. The clinical benefit persists at 6 months after the
procedure.”
Of the papers contributed to the literature subsequent to the cautionary and
analytical paper of Leong, Kubba, and White, in 2010, cited above,322 many are
cheering a “conservative inferior turbinoplasty approach.”323e328 Their canons
were often, unfortunately and regrettably, rife with limitations, for example, retro-
spective results, limited patient numbers, limited follow-up, often less than one
Table 9.1 Overview of study characteristics.

Number of Study Number of Patient age

Method studies First author Year Typesa patients range

Turbinectomy 5 Thompson 1989 1 22 9e15

Percodani 1996 1 38 9e16
Weider 1998 1 64 3e15
Segal 2003 1 227 3e10
Arganbright 2015 2 21 1e17
Submucosal diathermy 2 Rejali 2004 2 11 6e16
Montgomery 2011 1 47 3e14
Laser cautery 3 Pang 1995 1 20 6e15

Children and inferior turbinate reduction

Araki 2001 3 22 9e15
Rejali 2004 2 8 6e16
Submucous microdebridement 4 Chen 2007 3 120 9e14
Cheng 2008 4 51 3e12
Arganbright 2015 2 19 1e17
Manzi 2017 1 43 5e17
Radiofrequency volumetric tissue 5 O’Conner- 2007 3 93 2e9
reduction Reina
Sullivan 2008 4 86 1e17
Simeon 2010 3 9 6e16
Bitar 2014 4 32 6e17
Arganbright 2015 2 79 1e17
a
(l) Retrospective case series, (2) retrospective comparative case series, (3) prospective case series, and (4) prospective cohort study.
Table 9.1 from Komshian SR, Cohen MB, Brook C, Levi JR. Inferior turbinate hypertrophy: a review of the evolution of management in children.323

171
172 CHAPTER 9 Children and inferior turbinate reduction

Table 9.2 Pooled outcomes for each surgical technique.

Subjective
Method Improvementa Follow-up Complications

Turbinectomy 68%e93.4% 12e26 months Bleed (0%e2.6%)

Crusting
(0%e3.1%)
Synechia
(0%e6.6%)
Facial bone
malformation (0%
e0.44%)
Submucosal 36%e51% 23e72 months Bleed (13%e18%)
diathermy Pain (4%)
Anosmia (7%)
Laser cautery 50%e90% 18e32 months e
Submucous 93% 3e12 months e
microdebridement
Radiofrequency 93.6%e100% 6 weekse12 months Bleed (0%)
volumetric tissue Crusting
reduction (0%e8.6%)
Synechia (0%)
a
Outcomes are from reports from parental questionnaires and interviews.
Table 9.2 from Komshian SR, Cohen MB, Brook C, Levi JR. Inferior turbinate hypertrophy: a review of
the evolution of management in children.323

year, merely months, some devoid of objective and or subjective outcome measures
of “success,” and others using simply subjective “symptom grading tools.” Sadly, in
the present era, that’s just what’s available; however, some papers require mention
for their “conservative” mucosal preservation preference, necessarily functioning
in lieu of randomized controlled trials (RCTs), which similarly are currently nonex-
istent for children.
The 2015 paper of Jill Arganbright and colleagues from Children’s Hospital Col-
orado, Denver, University of Colorado (affiliated), presented a “conservative infe-
rior turbinoplasty approach” from a pediatric population chart review from
August 1, 2003, through August 1, 2013.328 The mean age of the 107 children stud-
ied was 10.5 years (range, 1.2e17.9 years). They appraised three different isolated
inferior turbinoplasty procedures which included:
(1) radiofrequency ablation in 72 children (67.3%)
(2) partial turbinate resection in 21 children (19.6%)
(3) microdebridement in 19 children (17.8%)
They observed no major complications and of the 107 patients, 63 parents
(58.8%) accomplished a postoperative telephone interview with a mean follow-up
of 4.55 years (range, 0.63e10.68 years). They documented that 34 patients
 Children and inferior turbinate reduction 173

(54.0%) required persistent postsurgical symptomatic medical management. At

the close, they concluded that:
“Inferior turbinoplasty showed overall utility and was safe and effective in the
treatment of nasal obstruction in children for whom medical management had
failed.”328
As previously presented, the honored work of Haight and Cole published in The
Laryngoscope in 1983,5 titled, “The site and function of the nasal valve” substanti-
ated that the head of the inferior turbinate is the posterior portion of the internal
nasal valve which acts as a flow limiting segment, an upstream resistor, which is
much more significant in altering air flow, capable of producing nasal obstruction
than an “obstructing adenoid” which is a downstream resistor. Unless an adenoid
“totally” obstructs the nasopharynx, an anterior inferior turbinate enlargement is
more significant than the adenoid in producing nasal airway obstruction and diffi-
culty breathing.
Regarding aggressive pediatric inferior turbinate reduction procedures, we note
the strikingly stunning 2003 paper of Samuel Segal and colleagues113 writing in
American Journal of Rhinology, MarcheApril edition, page 72, the last sentence
of their paper reads:
“Complete inferior turbinectomy should be considered in children who suffer
from extremely enlarged inferior turbinates and who have failed to benefit from
medical treatment or a more conservative surgical approach.” (Bold italics
added)
We vociferously and stridently support the adroit comments of David Kennedy,
then Editor-in-Chief of the American Journal of Rhinology, who in that same
MarcheApril edition, remarked, on page 69, regarding the work of Segal et al.113
“This study by Segal et al. reports no significant adverse effects from total infe-
rior turbinectomy in 227 children with nasal obstruction.” (Bold italics added)
Kennedy carefully yet purposefully continues cautioning the reader as follows:
“Although it is appropriate for the Journal to present alternative opinions and
ideas, it would seem appropriate for the reader to be cautious in considering to-
tal inferior turbinectomy in children until this cohort has been followed for a
significantly longer period of time.” (Bold italics added)
The follow-up period that Segal et al. reported was:
“. of whom 179 children had significant relief of nasal obstruction at the 1-year
follow-up.”
We add to Kennedy’s sagaciously reproving position by arguing that all authors
who operate on children have an explicit moral and ethical obligation to the follow,
report, and publish on the trajectory of these children as they passage into adult-
hood. This “rational” demand is obvious, as firm long-term follow-up data can be
174 CHAPTER 9 Children and inferior turbinate reduction

the sure-footed guide for all future surgeons when weighing the therapeutic options
for any and all future pediatric patients with symptomatically enlarged inferior
turbinates.
Until proof by solid evidence, with well-executed RCTs, we along with Leong,
Kubba, and White brashly and boisterously broadcast:
“Do not remove turbinates in children, since there is little evidence to support
turbinate reduction surgery in childhood!”322 (Bold italics with exclamation
mark added)
Unless there are a series of serious contradictory papers with powerful solid ev-
idence challenging the cautions announced by Leong et al., we hold that their
strongly held truths are self-evident and must be maintained until reversed and
thrown asunder, replaced by a newly minted “approximate temporary truth.”322
(Bold italics added)
Ultimately the question is, what’s the surgeon to do, when pressed to act, before
solid evidence from a well executed RCT arrives to successfully manage the
enlarged inferior turbinates of a child?
Remarkably, the mucosal-sparing approach has been “assumed” and “shown” to
be safe and efficacious for the time being and can, apparently, as some suggested, be
performed safely concurrently with other procedures such as tonsillectomy and
adenoidectomy or with adenoidectomy alone. Due to the very limited and likely
currently biased data and with marked uncertainty, regarding the “likelihood” of
possible long-term adverse effects, the decision to perform surgical turbinate reduc-
tion in children depends on individual circumstances and surgical “clinical judg-
ment,” because we lack the evidence from well-conceived and well-performed
RCTs.
For now, our preference is to respectfully follow the patients’ parents (or respon-
sible adult) holding authoritative dominance, along with courteously accepting the
“clinical judgment,” of a wise and honorable pediatric rhinologic surgeon.
Today, some type of “conservative” mucosal preserving turbinoplasty procedure
is the plausible treatment of choice, for children who fail the obligatory three-month
trial of intense medical management, as suggested by Argenbright et al. in their 2015
paper.328 Microdebrider submucosal inferior turbinoplasty (without bony resection)
with additional out-fracture (lateralization) of an inferior turbinate makes the most
sense at this juncture without guidance from any RCTs.
 CHAPTER

Medical journals: judging

the quality of the
editors, the peer reviewers,
plus the issue of plagiarism
10
Journals can be and often are extremely influential voices in setting standards of
accepting and adjudicating submitted research to accurately and unbiasedly
update and inform the profession. We depend upon the editors and the legions
of peer reviewers for supreme sagacity with soaring standards of integrity
when reviewing the submitted texts of thinking and data-rich experimental
findings. Our unwritten covenant with the peer reviewers and their editors is
they all act in the best interest of the profession, ultimately that is translated
into, for the best interest of the patient. In a 2016 paper, “Why Most Clinical
Research Is Not Useful,” by John Ioannidis,320 physician and professor at Stanford
School of Medicine and codirector of Meta-Research Innovation Center at
Stanford, claims that practicing physicians among others in the profession find
very little useful information in medical journals.320 He states that these medical
journals can affect the standards of acceptable research by having an external
group of reviewers assessing the clinical usefulness of papers to be published by
some objective “Journal Clinical Usefulness Factor” by saying:
“Overall, not only are most research findings false, but, furthermore, most of the
true findings are not useful. Medical interventions should and can result in huge
human benefit. It makes no sense to perform clinical research without ensuring
clinical utility. Reform and improvement are overdue.”320
With that said, he does not blame the medical journal editors for useless research
but sees that as an “opportunity” for improvements involving not only investiga-
tors “. but also institutions, funding mechanisms, the industry, journals, and
many other stakeholders, including patients and the public.”320 (Bold italics
added)
Previously, in a 2005 essay, “Why Most Published Research Findings are False”
Ioannidis asserted,

Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00010-X 175

Copyright © 2024 Elsevier Inc. All rights reserved.
176 CHAPTER 10 Medical journals

“Simulations show that for most study designs and settings, it is more likely for a
research claim to be false than true. Moreover, for many current scientific fields,
claimed research findings may often be simply accurate measures of the prevail-
ing bias.”329
According to Wikipedia, as of 2020, “Why Most Published Research Findings
are False” is the most widely accessed article from the Public Library of Science
with over three million views.
Additionally, Ioannidis in his 2014 article “How to Make More Published
Research True” he offers a thoughtful solicitous summary:
“To make more published research truedpossibilities include the adoption of
large-scale collaborative research; replication culture; registration; sharing;
reproducibility practices; better statistical methods; standardization of defini-
tions and analyses; more appropriate (usually more stringent) statistical thresh-
olds; and improvement in study design standards, peer review, reporting and
dissemination of research, and training of the scientific workforce.”330
While the opinion of John Ioannidis regarding the responsibilities of medical
journals was an oblique charge, a glancing tangential knock at medical journals
in general, a coalition of diverse investigators from Croatia, France, and Spain,
endeavored a straightforward direct inquiry of the medical journal collective
with the candid inquiry: “Is judging the quality of the editors and reviewers an
legitimate area of inquiry?”331 This March 2019 paper by Cecilia Superchi and
associates331 “was the first comprehensive review” searching for tools for deter-
mining the quality of peer review reports. They cited references reaching from
the original peer review referees of 18th century scientific journalism to the present
day, offering dispassionate judgements for evaluating and improving scientific
submissions. Numerous critics of the review process asked piercing perspicacious
questions such as:
1. Is peer review: a flawed process at the heart of science and journals?
2. Who reviews the reviewers?
3. Editorial peer reviewers’ recommendations at a general medical journal: are they
reliable and do editors care?
4. Rereviewing peer review.
5. Peer review for biomedical publications: we can improve the system.
6. Make peer review scientific.
7. Custodians of high-quality science: are editors and peer reviewers good enough?
Realizing the need for validated tools that define the quality of peer-reviewed
research reports, Superchi et al.331 scoured PubMed, EMBASE (via Ovid), and
The Cochrane Methodology Register (via The Cochrane Library) as well as Google
 Medical journals 177

finding 24 tools: 23 scales and one checklist, which could define the quality of peer
review reports although, not one tool defined the word “quality.” They concluded
that while:
“Several tools are available to assess the quality of peer review reports; however,
the development and validation process is questionable and the concepts evalu-
ated by these tools vary widely.”331
One out of four tools (25%) presented only one item asking the reviewer for the
“overall quality” of the work. Those tools with more items gave a “summary score”
without weighting of each individual scale. After all, how do you weight a scale? And
what do the tools measure? To complicate matters, scales are considered controversial
tools at best by some critical biostatisticians. The Risk of Bias tool clearly measures
the trial conduct by providing clear support for adjudication. Of course, Superchi et al.
pointed out that bias and uncertainty may occur using poorly designed tools:
“. that (“those tools”) are not evidence-based, rigorously developed, validated,
and reliable, and this is particularly true for tools that are used for evaluating in-
terventions aimed at improving the peer review process in RCTs, thus affecting
how trial results are interpreted.”331 Note (“those tools”) are added for clarity.
The serious effort for this critical work comes down to the importance of the peer
reviewer’s comprehension and understanding of the scientific work offered in the pa-
per under review. The consequences of the reviewer’s findings are obviously critical,
requiring astute interpretative rigor, so the editorial decision is scientifically justified.
Admirably, the authors plan to continue the quest for new validated quality assessment
tools for peer review reports in biomedical research. Their plans involve surveying
journal editors and authors alike by initiating and managing an international online
survey regarding the quality of peer reviewer’s reports for developing new evaluation
tools that can be used for appraising interventions aimed at improving the peer review
process especially in the analysis of randomized controlled trials (RCTs).331
Since the first international Peer Review Congress, about 30 years ago,
Drummond Rennie former member of the Commission on Research Integrity for
the US Public Health Service, and former president of the World Association of
Medical Editors writing in Nature in 2016 made his plea in the paper’s title:
“Let’s Make Peer Review Scientific.”332
There are problems in medical journal paradise. There are accusations that
almost any hypothesis of trivia or a tattered fragmented thread of an idea can be pub-
lished because evidence abounds revealing that peer reviewers rarely receive formal
preparation for their responsibility. Therefore, it’s not surprising that their compe-
tence, especially in biostatistics, and overall capability to uncover errors and detect
reporting deficiencies is unacceptably wanting. Other studies showed that:
“. there is still a lack of evidence supporting the use of interventions to improve
the quality of the peer review process.”332
178 CHAPTER 10 Medical journals

Therefore, the need is urgent for improving the quality of peer review reporting and for
finding instruments (tools) for evaluating and improving the quality of those reports.332
Merely a few years ago in 2017, in Chicago, Illinois, David Moher presented a
plenary talk at the eighth International Congress on Peer Review and Scientific Pub-
lication (below) entitled:
Custodians of High-Quality Science: Are Editors and Peer Reviewers Good
Enough? which is available at: https://www.youtube.com/watch?
v¼RV2tknDtyDs&t¼454s.

Finally, a closer look at the dark side of medical journal’s lunar landscape, scruti-
nized for sure, as there are malevolent forces in our medical solar system even among
us in their guise as nobles in our glorious profession. Enter the sanguine orthopedic
honorable triad of Joseph Buckwalter, Vernon Tolo, and Regis O’Keefe orthopedists
all, asking “How do you know it is true? Integrity in research and publications: AOA
critical issues.” These three musketeers, armed with truth, blasted some of the noto-
rious evil perpetrators and perverts of the sacred scientific trust. Note: The Three Mus-
keteers was written333 by the French novelist Alexandre Dumas in 1844 about heroic,
honorable, moral men fighting for justice. As surgeons, Buckwalter, Tolo, and
O’Keefe focused on orthopedic practice, but their cautions and admonitions apply
to all in medicine. Explicitly, and without question, we all acknowledge that scientific
research findings have led to momentous changes in medical and surgical practice to
the betterment of our human kind. Research can certainly be deliberately biased owing
to lucrative patents owned by investigators with commercial consulting arrangements
within the high drama of a competitive research environment.
Disgustingly, some current research has been characterized:
“. by an increase in plagiarism, falsification or manipulation of data, selected
presentation of results, research bias, and inappropriate statistical analyses.” 333
(Bold italics added)
 Medical journals 179

In homage to the exquisitely laudable efforts of Buckwalter, Tolo, and O’Keefe,

we have chosen to reproduce a portion of their applicable text, citing the maleficence
we must all be alerted to, never naı¨ve please, always aware to the possibility of
crimes and misdemeanors in the revered name of medical research.333
“The misrepresentation of natural observation has existed for as long as scientific
research has been recorded. Ptolemy, the renowned second-century Egyptian
astronomer, recorded astronomical measurements that he could not have made.
Ptolemy’s work, purporting to prove that Earth was the center of the universe,
influenced science and philosophy for centuries. Copernicus, who revolutionized
our understanding of both Earth and man’s place in the universe, was accused of
heresy when he reported a conflicting celestial configuration based on appro-
priate scientific methods and accurate measurements. The legendary physicist
and Nobel laureate Robert Millikan (1868e1953), who discovered the negative
charge of the electron, selected only 58 of 140 observations for inclusion in his
scientific presentations. While this selective use of data likely improved precision
and the credibility of his claims, it did not truly represent his actual scientific find-
ings. Sir Cyril Burt (1883e1971), a noted British psychologist, fabricated
(extrapolated) data to show that human intelligence is 75% inherited. His work
influenced educational programs and policies for generations.”333(Bold italics
added)

“From 1996 to 2008, Dr. Scott Reuben published a series of articles that exam-
ined the potential role of cyclooxygenase-2 (COX-2) specific inhibitors in control-
ling postoperative pain following orthopedic surgery. In a series of carefully
designed and double-blind placebo-controlled studies, Dr. Reuben established
that Celebrex (celecoxib; Pfizer), Bextra (valdecoxib; Pfizer), and Vioxx (rofe-
coxib; Merck) dramatically improved pain management for patients undergoing
joint replacement, spine fusion, and anterior cruciate ligament reconstruction
and decreased the complications associated with the standard use of opiates.3
Dr. Reuben, a Professor of Anesthesiology and Pain Medicine at Tufts and the
Chief of Acute Pain at Baystate Medical Center, was widely recognized for revo-
lutionizing pain management for orthopedic patients. A 2007 editorial in Anes-
thesia and Analgesia stated that Reuben had been at the “forefront of
redesigning pain management protocols” through his “carefully planned” and
“meticulously documented studies.(333)”4(Bold italics added)

“In 2008, it was discovered that two abstracts submitted by Dr. Reuben for Bays-
tate Medical Center’s Annual Research Week lacked institutional review board
approval. Investigation showed that Dr. Reuben had never enrolled patients or
performed the studies described in the manuscripts. Further review resulted in
Baystate requesting medical journals to retract a combined total of 21 of Dr. Reu-
ben’s papers. Dr. Reuben’s advocacy for COX-2 inhibitors to treat postoperative
pain appeared in reviews, textbooks, and practice guidelines. Beginning in 2000,
180 CHAPTER 10 Medical journals

Reuben advocated that physicians should shift from the use of first-generation
nonsteroidal antiinflammatory drugs to the use of Vioxx, Celebrex, and Bextra
to treat musculoskeletal pain.3 Reuben urged the United States Food and Drug
Administration (FDA) not to restrict use of the drugs he studied, citing their effi-
cacy and safety. Drug companies organized educational programs and symposia
on the basis of Reuben’s reports. Various editorials noted that “millions of ortho-
pedic patients’ pain management has been affected by Dr. ha ha Ha ha-ha did you
have dinner ready Reuben’s research” and “Reuben’s studies led to the sale of
billions of dollars of Celebrex and Vioxx.”5,333(Bold italics added)
Authors’ (EBK, OF) note from Wikipedia: “Scott Reuben plead guilty to “health-care fraud” and
was convicted on February 24, 2010 and served six months in federal prison. His Massachusetts
medical license was permanently revoked.”

“Reuben’s work had actually come under scrutiny as early as 2007, when several
anesthesiologists noticed his studies never showed negative results [4]. Greg
Koski, former director of the Office for Human Research Protections, said the
fraud was unusual because Reuben was able to carry it on for almost 13 years
without being caught by the peer review process.”(Bold italics added)

“In 1998, Dr. Andrew Jeremy Wakefield and coauthors published a study in The
Lancet of 12 children, suggesting a link between the measles, mumps, and
rubella (MMR) vaccine and autism.6 The results were widely reported by the me-
dia, were popularized on a variety of web sites, resulted in the refusal of vacci-
nation by many parents, and led to lawsuits by parents of autistic children
against vaccine manufacturers. The Lancet and the press later learned that Wake-
field had received a $110,000 payment from the Legal Aid Board prior to pub-
lishing the paper. The Legal Aid Board was seeking evidence that could be used
in lawsuits against vaccine manufacturers and, following publication of the
article, provided an additional $674,000 payment to Wakefield. A retrospective
review of the data used by Wakefield revealed that the diagnosis and/or dates
of records were changed for all 12 children in the publication report so as to
support the author’s conclusions.7,8 The Lancet partially retracted Wakefield’s
paper in 2004 and later issued a full retraction. The General Medical Council
of the United Kingdom found Wakefield guilty of professional misconduct
(autism fraud) and revoked his medical license. However, public suspicion that
vaccinations can cause autism persists. Vaccination rates have dropped sharply
in many countries, including the United States, and this drop in vaccinations is
a major contributor to the increased incidence of measles and mumps, resulting
in outbreaks of the diseases and deaths in multiple countries.9 Subsequent studies
have demonstrated no link between the MMR vaccine and autism. Position
statements supporting vaccination and the absence of a link with autism have
been released by the Centers for Disease Control and Prevention, the American
Academy of Pediatrics, the Institute of Medicine, the National Academy of Sci-
ences, and the UK National Health Service”.333 (Bold italics added)
 CHAPTER

Review, finishing touches,

and closure
11
Following our literature review, apparently other observers also agree with us that
the empty nose syndrome (ENS) is a strikingly important yet uncommon clinical en-
tity because of the profound physical suffering especially with breathing difficulties
and a surprisingly high incidence of disabling emotional anguish experienced by so
many of these patients.2e4,18e28,33,73,76,214,335,345,353,355
The difficulty of breathing is frequently associated with dyspnea (breathlessness),
the so-called paradoxical nasal obstruction with a sense of suffocation despite a “wide
open” nasal airway.18e21,55,347 The emotional torment encountered by ENS patients is
astonishingly high, over 50% in the Mayo study18, and in most other accounts also,
with anxiety, depression, and suicidal ideation (near 43% in one study340) are the
usual; mental misery an unexpected comorbidity.20,33,62,73,74,76,334e350
ENS, a secondary atrophic rhinitis (AR), is almost always iatrogenic in origin
excluding those resulting from the inexorable and inevitable aging process which
we have documented or from an infectious process produced by Klebsiella pneumo-
niae ozaenae, which we consider as primary AR.
Yes, ENS, most often, occurs secondary to an iatrogenic reduction of turbinate
tissue, secondary to therapeutic turbinate trauma (TTT), with symptoms that are
of unpredictable intensity. Fundamentally, this occurs secondary to a procedure on
the turbinate(s) which injures immeasurable amounts of functioning turbinates
mucosal and submucosal (lamina propria-stroma) tissue. The intervention is usually
and predominately designed to reduce an enlarged inferior turbinate to improve a
patient’s breathing function; however, in some individuals the turbinate procedure
of puzzling and inexplicably produces ENS. In the section below, we will explore
some theories regarding the etiology and pathophysiology of ENS.
We have personally cared for more than 300 ENS patients. Based on our reading
of the literature, to avoid ENS, we have emphasized the need for conservative sur-
gical intervention when treating patients with inferior turbinate enlargement (“hy-
pertrophy”) who failed intense medical management. When treating those souls
suffering from ENS, our required responsibility is for sensitive compassionate
comprehensive care which we will proffer for you in detail below.
Unfortunately, currently (2022) there are no curative or even subtotally
restorative therapies for ENS though we will present recent results, promising pro-
nouncements from the literature, regarding surgical options assuring favorable
“long-lasting” or “long-term” benefits for our ENS patients, although there is no
long-term follow up, usually in months not years.

Empty Nose Syndrome. https://doi.org/10.1016/B978-0-443-10715-3.00011-1 181

Copyright © 2024 Elsevier Inc. All rights reserved.
182 CHAPTER 11 Review, finishing touches, and closure

We condensed and concentrated much, certainly not all, of the currently known
knowledge regarding ENS (up to the first of November 2022), with an exhaustive
extensive bibliography, into a single “comprehensive” resource so each practitioner
may reach their own conclusion(s) about this underappreciated syndrome along with
the inestimable risks associated with any turbinate reduction procedure for
improving nasal breathing, especially when nasal function (physiology) is often
seemingly unseemly slighted or ignominiously grossly and deliberately ignored.
Oddly, even presumably “minor” turbinate trauma may subsequently result in
ENS, weeks, months to years later, superimposed, as it were, on the aging process
with its inexorable dwindling capacity for fulfilling fundamental functional
processes.
After initial recognition, preliminary treatment for ENS usually involves topical
medications for crust and odor control along with pain management (post-traumatic
neurogenic pain) and psychiatric evaluation with treatment, when required, since the
psychologic burden and emotional suffering are significant, as over 50% of ENS pa-
tients experience emotional distress, anxiety, and depression, many with suicide
ideation, which, in some cases, was not evident prior to the onset of ENS.
Possible surgical intervention is considered as a last resort since, currently, the
postsurgical data lack long-term (years) proof of “permanent” success (relief of
symptoms), although most recently (2020e22) a number of reports have assured,
with data, a reduction in symptoms after specific surgical intervention(s), which
we will analyze and discuss in Section 8, Surgical treatment of ENS, below.
We offer deliberations and reflections regarding safe management of nasal
airway obstruction secondary to pathology of the inferior turbinate. We present
four different classification systems for inferior turbinate enlargement (“hypertro-
phy”) and summarize the “latest thinking” with a few evidence based proposals
for inferior turbinate management from the literature; intending and expecting to
avoid ENS.
Presently, ENS is best prevented by minimizing inferior and middle turbinate tis-
sue trauma during turbinate reduction (modification) procedures, period. Future ran-
domized controlled trials (RCTs) are indispensable to definitively answer the
inferior and middle surgical treatment questions.
With the opening sentence to Chapter 4 “Treatment options for ENS,” we are
confronted with the reality as to why the “empty nose syndrome” is so challenging;
not only the challenge of accurate diagnosis and the fact that the mean time from
therapeutic turbinate trauma to diagnosis is often measured in months to years,
and as a consequence, we emphasize the need for prevention by intelligent manage-
ment of symptomatic inferior turbinate hypertrophy. These facts require you, dear
readers, to enter into the world of the turbinate anatomy, physiology, surgical de-
bates, evidence-based medicine (EBM), and the moral and ethical search for data-
driven turbinate studies that will guide we surgeons to provide successful patient
care.
With our wide-ranging bibliography of almost 400 references and our historical
journey over the past 100 years of turbinate surgery, in Chapter 5, plus the variety of
 Review, finishing touches, and closure 183

contemporary management options for treating enlarged symptomatic inferior turbi-

nates are presented in Chapter 7 as we endeavored to give the text the extensive
comprehensive sense of accurate authoritativeness.
The literature review was the consequential harbinger for necessarily enter-
taining EBM. EBM advised, rather demanded, a most sensible and logical approach
to inferior turbinate reduction which to date (2022) is based on the landmark work of
Professor Desiderio Passali, MD, and his co-workers who performed a randomized
turbinate study, following their 382 patients, carefully collecting objective breathing
and physiologic data, at four years and six years after surgery. Passali et al.211,216
concluded:
“After 6 years, only submucosal resection resulted in optimal long-term normal-
ization of nasal patency and in restoration of mucociliary clearance and local
secretory IgA production to a physiological level with few postoperative compli-
cations. We recommend, in spite of the greater surgical skill required, submucosal
resection combined with lateral displacement as the first-choice technique for the
treatment of nasal obstruction due to hypertrophy of the inferior turbinates.”211
Chapter 8 is a uniquely interesting chapter as we grappled with ethical issues
related to advances in medicine especially concerning introducing new and novel
surgical procedures including the potential role of sham surgery and its application
to RCTs when an operation is indicated.
We present an up-to-date discussion of the Consolidated Standards of Reporting
Trials (CONSORT) requirements, propensity score matching (PSM), clinical prac-
tice guidelines (CPGs), and the entire issue of conflicts of interest (COI) as these
topics are all considered, deliberated, and explored in depth since rhinology is still
coping with these issues in a very practical every-day sense.
We endeavored to broaden the discussion beyond the diagnosis and treatment op-
tions of the “empty nose syndrome” as we explored EBM its origins, its applications,
and limitations especially as related to the direction of future rhinologic research in-
vestigations resulting in an enlightened approach to practical clinical practice.
The dilemmas of the rhinologist are examined when data from RCTs are unavai-
lable since “the crucial study” was never performed. The argument of empiricism
(evidence first) versus rationalism (clinical judgment) takes center stage specifically
when data from a “definitive” RCT are “limited, incomplete, inconclusive, conflict-
ing, or starkly nonexistent.” We, authors, argue and maintain that when empirical
data are unavailable, then experience and clinical judgment governs as the indis-
pensable key rational alternative. The ethics of using placebos are also considered
along with the distinction and differentiation between “research” and “care” as in
surgical research trials and surgical clinical care. The nature of medical progress
is a subject that is also examined especially since the cited work of Prasad et al. from
the National Institute of Health (NIH) revealed that “the reversal of established med-
ical practice is common and occurs across all classes of medical practice.”271 In
fact, Prasad et al. found that 40.2%, of established practices they reviewed (2044
184 CHAPTER 11 Review, finishing touches, and closure

original articles), was reversed (discontinued) because that practice was either use-
less or harmful.271
The work of Prasad et al. clarified the fact that medicine aspires to apply the
finest, most accurate, information obtainable at the time, which allows for “knowl-
edgeable guesses,” which of course, is subject to change.
We, as physicians and surgeons are obliged to endure “uncertainty” acknowl-
edging the reality that medical theories and practices are subject to dislocation,
disruption, continuous change, and improvements since that is the nature of medical
progress. Realize that there is a temporal quality to truth as the work of Sir Karl R.
Popper, the 20th century philosopher of science, instructed us, by introducing the
concept of an “approximate temporary truth”.
Regarding children, Chapter 9, again there is a shockingly scandalous lack of
RCTs for guiding the surgeon toward intelligent inferior turbinate surgical decisions
for the pediatric populations. Leong and colleagues (2010) thought that:
“There is currently little evidence to support turbinate reduction surgery in
children. The role of surgery, if any, has not been properly examined. Further-
more, the long-term effects on nasal airflow dynamics, nasal physiology and
long-term complications remain to be studied.”322
Despite that fact of “little evidence” and “no guidelines,” we suggest a “rational”
surgical approach, for now, which, after our literature study, we, your authors (EBK,
OF), advocate for children that:
“Some type of “conservative” mucosal preserving turbinoplasty procedure with
an additional out-fracture (lateralization) for children who fail the obligatory
three month trial of intense medical management without guidance from any
RCT.”
At a minimum, until the arrival of convincing rational guidelines from a well-
conducted RCT, we make the “moral and ethical” demand that surgeons who operate
on these youngsters, must follow, reported and published on the trajectory of these
children as they passage into adulthood. It’s critical that we establish and set a “high
bar” before approving and accepting any new surgical procedures or technologies.
An academically yet ultimately pragmatic and consequential Chapter 10 deals
with medical journals and issues regarding judging the quality of peer reviewers
which of course has consequence as to which articles are published which in turn
can profoundly influence our medical and surgical practices. The all-inclusive chal-
lenging question of evaluating journal editors and peer reviewers is addressed, and
the need for validated tools for assessing the quality of peer review reports is pre-
sented and considered.
We cite, demanding reflection, the 2016 provocative paper by John Ioannidis,
MD, professor at Stanford School of Medicine, in which Ioannidis argues that
most clinical research is “Not Useful.”320
In this, our last chapter, Chapter 11 Review, Finishing Touches, and Closure, we
journey through and beyond the “empty nose syndrome,” appropriately so, as we
 1. Managing the empty nose syndrome patientdsummary 185

contemporaneously, almost up to the very minute, offer the overview as to where we

are and where we, as a profession, need to go first protecting patients by preventing
ENS when we operate on turbinates and when needed, treating those patients
plagued with “empty nose syndrome.”
We demand lofty goals for medical science to seek and achieve that any noble
future direction in medicine must be based on high-quality validated evidence-
based published studies that provide actionable steps to protect the interest of all
of our past, present, and future patients, short of that lofty moral aspiration, we
rely on experienced clinical judgment, realizing that it may eventually prove to be
biased and flawed requiring revision, “safety” first followed by “useful” in all her
glory.

1. Managing the empty nose syndrome patientdsummary

1.1 Empty nose syndrome exists
In 2020, the American Rhinologic Society (ARS) website stated:
“The exact incidence of ENS is currently unknown. There are still thousands of
patients experiencing ENS.”
Apparently, ENS is more common than originally thought, with over 80 litera-
ture citations listed in our Table 1.1 from 2001 to November 1, 2022 acquired
from the PubMed database. ENS appears on numerous worldwide websites and in
multiple languages including: Arabic, Chinese, Dutch, French, German, Hebrew,
Italian, Korean, Portuguese, Russian, Spanish, and Turkish among others. The evi-
dence is mounting that ENS is now recognized as a valid (authentic) physiologic dis-
order with a rising flood of research and clinical interest with over 40 papers listed
on the PubMed database with Empty Nose Syndrome in the title over the past four
years alone, 2019e22, Table 1.1.

1.2 Pertinent nasal physiology

The mucosa is the organ of the nose. Nasal anatomy is created to serve our physio-
logical needs. Olfaction, breathing (respiration), and defense are optimized when air
flows through the nose. Regarding nasal breathing, the nose offers a critical upper
airway resistance, provided by the internal nasal valve area, which includes the
head of the inferior turbinate. The nose creates the proper resistance (“resistor
function”dthe internal nasal valve area) for breathing; lung expansion, enhancing
venous return. Charging the inspired air (“diffusor function”dturbulent air flow)
for the sense of breathing, providing warmth (temperature) and moisture (humidity)
to the inspired air enabling ideal CO2 and O2 exchange to occur optimally at the
alveolar level, which is after all, respiration.
186 CHAPTER 11 Review, finishing touches, and closure

The trigeminal nerve mediates the perception of normal nasal airflow by action
potentials from the transient receptor potentials melastatin 8 (TRPM8) receptors that
are located in the mucosa, goblet cells, and vessels, not in the connective tissues.
These TRPM8 receptors, the trigeminal “cool” thermoreceptors, are triggered by
the wall shearing stress effects of the inspired air currents cooling of the nasal mu-
cosa providing the sense of normal breathing.33,74,353e355
The surface area of the nasal mucosa and submucosa (lamina propria, stroma) is
increased with intact turbinate tissue, allowing the defensive mechanisms of the nose
to protect (defend) us in the following four ways: mechanical, humoral, cellular, and
various nasal reflex defenses, which we have summarized and presented for the
reader earlier in the text in Chapter 1. Especially interesting are the humoral de-
fenses that include immunoglobulins IgA and IgG and the cytokines that are released
by white blood cells and fibroblasts including the important interleukins (Il) include:
Il-4, Il-5, Il-8, and Il-13. Antimicrobial secretory proteins include: lactoferrin (Lf),
lysozyme (Ly), and human beta-defensin 1 (hBD-1) are also components of the nasal
humoral defense system.
The other interesting defense system is the cellular defense living and breathing
within the submucosa (lamina propria, stroma) including the dendritic cells that pre-
sent foreign proteins to T and B lymphocytes designed for initiating immune re-
sponses. Remarkably dazzling.

1.3 Symptoms of ENS

The hallmark symptoms of ENS are fluctuating, variable, and protean including
many of the following symptomatic indicators of ENS listed below:
1. Paradoxical nasal airway obstruction (nasal “congestion,” difficulty breathing,
“breathlessness,” often with a sense of suffocation)
2. Nasal crusting, nasal dryness (“rhinitis sicca”), bleeding (varying degrees of
epistaxis)
3. Inability to feel nasal airflow
4. Foul (fetid) odor (often noted by others) with thick nasal discharge and post-
nasal “drip”
5. Anosmia or hyposmia
6. Headache
7. Pain, localized nasal facial pain (post-traumatic neuropathic pain)
8. Disturbed sleep (with secondary symptoms of fatigue and lethargy)
9. Aprosexia nasalis (inability to concentrate)
10. Disturbance in the sense of “well-being”
11. Impaired quality-of-life
12. Emotional comorbidity (anxiety, clinical depression, suicidal ideation)
Remarkably, not astonishingly, the mental health burden (emotional comorbid-
ity) experienced by ENS patients is generally over 50%, including anxiety, depres-
sion, and suicide ideation approaching 43% in one study.18,20,33,62,73,74,76,334e350
 1. Managing the empty nose syndrome patientdsummary 187

ENS patients with suicidal ideation (thoughts) consistently experienced and

interpreted their symptoms as severe, and as such these patients must be identified
to avert a catastrophic tragic ending. As a consequence of this reality, systematic
“routine” psychological evaluation is mandatory as part of the medical assessment
and management of all diagnosed ENS patients; unquestionably needed before
any contemplated surgical intervention as the effect of “surgical failure” could pro-
foundly and adversely impact a peak psychologically vulnerable person. The self-
rated questionnaires such as Beck Anxiety Inventory (BAI) or Generalized Anxiety
Disorder (GAD-7) for anxiety or the Beck Depression Inventory, updated version,
(BDI-II) or Patient Health Questionnaire (PHQ-9) for depression are reliable diag-
nostic tools and aids for determining anxiety and depression.
Summary of applicable diagnostic investigations for ENS:
1. History of previous turbinate surgery and symptomsdcan be strongly suggestive
for ENS
2. Endoscopy-nonspecific, but can document turbinate surgical resection
3. Imaging-nonspecific, but can document turbinate surgical resection
4. Testing/questionnaire for ENS
a. Breathing tests-nonspecific
b. Computational fluid dynamics (CFD)dcan be strongly suggestive for ENS
c. *Cotton test-specific for ENS
d. Menthol test-impaired in ENS
e. Nasal nitric oxide (nNO) test levelsdreduced in ENS
f. Olfactory testing-nonspecific
g. Tissue biopsydcan be strongly suggestive of ENS
h. *Questionnaire-empty nose syndrome 6 item questionnaire (ENS6Q)dcan be
strongly suggestive of ENS
i. *Questionnaire-the 22-item Sinonasal Outcome Test (SNOT-22)
j. *Questionnaire-the Nasal Obstruction Symptom Evaluation (NOSE) Instrumentd
grading the degree of nasal obstruction
k. Psychological testingdwith self-rated questionnaires are nonspecific but
supportive
1. * Generalized Anxiety Disorder (GAD-7) for anxiety
2. * Patient Health Questionnaire-9 (PHQ-9) for depression
* See Appendix for details: The appendix contains seven items: (1) a brief history of Professor
Maurice H. Cottle, MD; (2) the Empty Nose Syndrome 6 questionnaire (ENS6Q); (3) the
Sino-Nasal Outcome test 20-25 (SNOT20-25) for ENS; (4) Nasal Obstruction Symptom Eval-
uation (NOSE) Instrument; (5) the cotton test, and how to perform it; (6) the questionnaire
Generalized Anxiety Disorder (GAD-7); (7) the Patient Health Questionnaire-9 (PHQ-9)
for depression.
Consider the “spectrum of disease” concept. The diagnosis of any illness or dis-
ease process is made when that particular process becomes manifest, obviously
symptomatically observable, first to the patient, then to the physician. Most often
188 CHAPTER 11 Review, finishing touches, and closure

termed, the onset, as the initial stage of the clinical presentation of any illness. In
some, disease development evolves, becoming a clear clinical illness. In others,
the disease process may remain subclinical, somewhat asymptomatic, or range
from mildly manifest and manageable to severe and intractable or even fatal (sui-
cide); as was the case with four of our patients (neither of us operated on any of these
unfortunate despondent suicidal ENS patients). This range and scope of illness is
titled the “spectrum of disease.”
When considering and processing the range of symptoms and treatment options
for ENS patients, it is valuable to adopt this longitudinal “spectrum of disease” view
about this protean, fluctuating, oscillating disease process; trying to identify the
“precise” stage within the “continuum of disease” that you are meeting in a partic-
ular ENS patient can be of tremendous utility. If early in the course of illness you
may initially choose medical management including psychologic support and
referral after positive psychological screening tests, as this emotional component
may require the most aggressive management at this juncture or at any time you
meet the ENS patient during the continuum of their disease development, especially
before contemplating any invasive treatment plan, especially surgery, but including
injections.
Thinking broadly, we classify ENS as an overlapping physical, emotional, pri-
marily noninfectious, secondary AR, iatrogenic disorder.
Currently there are no absolute diagnostic standards for ENS; however, the diag-
nosis is practically and predictably established by the patient’s exclusive history of
previous nasal turbinate reductive treatment, symptoms of paradoxical nasal airway
obstruction (difficulty breathing despite a nonobstructing “open airway”), crusting,
dryness, feeling of an open airway, and suffocation with frequent emotional symp-
toms of anxiety and depression. The intranasal examination with nasal endoscopic
inspection is supplemented by computed tomography (CT) of the nose and paranasal
sinuses, which is suggestive but not diagnostic, unless the turbinates have been sur-
gically removed (resected) clearly leaving the telltale remaining surgical stumps as
evidentiary proof.

1.4 History and symptoms

The history of previous nasal surgery explicitly turbinate surgery more specifically
an inferior turbinate procedure although middle turbinate modification may also her-
ald the arrival of ENS although less frequently than inferior therapeutic turbinate
trauma. The 22-item Sinonasal Outcome Test (SNOT-22) is extremely helpful in
diagnosing ENS as it is a validated patient symptom questionnaire.350 The empty
nose 6 item questionnaire (ENS6Q) is valuable, very strongly suggestive for ENS
when the symptom score exceeds 10.5 (>11) of their subjective symptoms on the
ENS6Q.31 For the empty nose 6 item questionnaire (ENS6Q), the scoring ranges
from 0 to 5 with 0 meaning no symptoms to 5 with extremely severe symptoms
and with a total score over 10.5 (>11) is suggestive of ENS.31
 1. Managing the empty nose syndrome patientdsummary 189

1.5 Nasal endoscopy

Nasal endoscopy with the frequent finding of surgically truncated turbinates found
on intranasal examination correctly correlates with the patient’s history in many
cases, although not all.

1.6 Imaging
Imaging, especially CT is exceptionally effective in visually documenting resected
turbinate tissue(s). The CT scan often displays a cavernous expansion of the intra-
nasal airway with the absence or reduction of various amount of one or both inferior
turbinates and reduction or absence of one or both middle turbinates which have
been previously surgically reduced or resected. On the other hand, at times, the
CT appears “normal,” yet the patient has had a previous turbinate procedure or pro-
cedures and the functional integrity of the turbinate(s) has been functionally
compromised; a blatant case of ENS may exhibit normal appearing intranasal struc-
tures, especially when a submucosal turbinoplasty or non-surgical Turbinate
Reductive Adjunctive Procedure (n-s TRAP) has been performed.

1.7 Testing in ENS

1.7.1 Cotton testdspecific for ENS
There are specific and nonspecific tests for ENS, and the cotton test is considered
specific, which involves placing a dry cotton (plug) pledget (in an unmedicated
nose) in the region of the previously resected structure(s), usually in the region of
previously resected head(s) of the inferior turbinate(s). The test is “positive” if the
patient reports a reduction (lessening) of their nasal symptom severity score on
repeat ENS6Q (compared to pretest ENS6Q score), while the cotton (plug) pledget
is in place.32

1.7.2 Olfactory testdnonspecific for ENS

Olfaction tests are nonspecific, suggestive but not diagnostic. We use the modified
Sumner olfactory test for all our rhinology patients.147

1.7.3 Menthol testdimpaired in ENS

In a number of separate studies, the menthol detection test was established to be
lower in patients with ENS.43,335,355,358e359

1.7.4 Breathing testsdnonspecific for ENS

The breathing tests, including rhinomanometry and acoustic rhinometry, are nonspe-
cific and not diagnostic of ENS.333,345

1.7.5 Nasal nitric oxide test levelsdreduced in ENS

Low nNO levels are usually seen in ENS.344
190 CHAPTER 11 Review, finishing touches, and closure

1.7.6 Computational fluid dynamicsdstrongly suggestive for ENS

Currently there are a number of CFD studies for ENS patients.335,354,361e364 The re-
sults are specific for ENS in that patients with ENS demonstrated reduced nasal air
flow rates at the inferior regions of the nasal cavity, where they should normally be
higher, as the airflow distribution shifts upward toward the region of the middle
meatus. The intimate interaction between the air flow column and the nasal mucosa,
measured as wall sheer stress, was decreased. These findings of lower flow rates with
lower resistance values strongly suggest ENS; although they are not absolutely diag-
nostic, these findings are consistent in ENS patients.335,354,361e364

1.7.7 Psychological testingdnonspecific but supportive

“*Self-rated questionnaires such as Beck Anxiety Inventory, (BAI) or Generalized
Anxiety Disorder (GAD-7) for anxiety or the Beck Depression Inventory, updated
version, (BDI-II) or Patient Health Questionnaire (PHQ-9) for depression are reliable
diagnostic tools and aids for determining anxiety and depression. The Minnesota
Multiphasic Personality Inventory (MMPI) assesses personality style rather than
explicitly designed for depression/anxiety. If patients are outpatients and not severely
compromised, the self-rated scales are adequate and acceptable. However, if a person
is psychiatrically or neurologically ill requiring intensive services such as hospitali-
zation, then the patient should be assessed with an observer-rated scale such as the
Hamilton Anxiety Scale or the Hamilton Depression Scale.”
*Personal communication: Teresa A. Rummans, MD.
Donald and Lucy Dayton Professor of Psychiatry, Mayo Clinic.
The following self-rated questionnaires are very valuable in managing ENS pa-
tients as they help identify anxiety and depression which may require professional
emotional support:
1. Generalized anxiety disorder (GAD-7)
2. Patient health questionnaire (PHQ-9)
3. Beck anxiety inventory (BAI)
4. Beck depression inventory, updated version (BDI-II)
Note: The BAI is not in the public domain, but it is a copyrighted measure by the
developer, Dr. Aaron T. Beck. The measure can be purchased from Pearson Assess-
ment at www.pearsonassessments.com.

1.7.8 Tissue biopsydstrongly suggestive

Wu et al. (2021) presented the histological review of some 17 ENS patients and a
control group of six people.365 Tissue biopsies were performed at the midpoint of
the inferior turbinate revealing squamous metaplasia (76%), submucosal fibrosis
(94%), and a lower submucosal gland population when compared to controls. In
their ENS patients’ samples, the nasal respiratory epithelium was characteristically
intact. Additionally, a unique histological change called goblet cell metaplasia was
 1. Managing the empty nose syndrome patientdsummary 191

found in the ENS group, and this ENS group had a significantly lower expression
level of transient receptor potential melastatin subtype 8 (TRPM8).* Immunohisto-
chemical staining was performed for TRPM8 and is found in the epithelium, goblet
cells, and in the submucosal vessels.
*The transient receptor potential melastatin subtype 8 (TRPM8) is a nonselective, multimodal
ion channel, activated by low temperatures (<28
C), pressure, and cooling compounds
(menthol, icilin). Experimental evidences indicated a role of TRPM8 in cold thermal trans-
duction . From González-Muñiz R, Bonache MA, Martı́n-Escura C, Gómez-Monterrey.
Recent Progress in TRPM8 Modulation: An Update. Int J Mol Sci. 2019 May 28; 20(11):
2618. https://doi.org/10.3390/ijms20112618. PMID: 31141957; PMCID: PMC6600640.
Gill et al.33 believing ENS as a true physiologic disorder involving altered nasal
airflow, not primarily an “uncloaked psychiatric problem,” held that the major ad-
vances for assessing and diagnosing ENS patients included the following:
“ENS is increasingly becoming recognized as a legitimate, physiologic disease
entity. As such, it is important for clinicians to understand the most up-to-date
diagnostic tools to assess ENS, confirm the diagnosis, and create a more stan-
dardized means to counsel these complex patients. For the purposes of this review
article, we assume that ENS is a true sinonasal disease with a physiologic foun-
dation consistent with altered nasal airflow. We review these diagnostic tech-
niques as well as mental health comorbidities associated with ENS”.33
Emphasized above, the empty nose 6 item questionnaire (ENS6Q) is valuable as
it’s very strongly suggestive for ENS when the symptom score exceeds 10.5 (>11)
of their subjective symptoms on the ENS6Q.31 The cotton test reported by Thamboo
et al. used the ENS6Q to validate an office-based physical examination maneuver as
another provocative supportive adjunct in confirming the diagnosis of ENS. The test
itself was accomplished in the absence of any topical intranasal sprays, where a fash-
ioned plug (pledget) of cotton was placed in the patient’s inferior meatal space that
was partially or completely devoid of inferior turbinate tissue. The cotton remains in
place for approximately 20e30 min, and the ENS6Q is performed prior to testing;
after 20e30 min while the cotton is in place (situ), the ENS6Q is repeated and for
one final time after cotton removal, a third time.32
To review, the ENS6Q is obtained prior, during, and after the insertion of the cot-
ton for the cotton test ENS6Q which occurs during three conditions:
a. Precotton placement, ENS6Q testing
b. Cotton in place (situ), after 20e30 min, ENS6Q testing
c. Postcotton (after removal), ENS6Q testing
1. The ENS6Q, which is a patient reported outcome measure that was validated
using the SNOT-22.31
2. The cotton test helps confirm the diagnosis of ENS using the ENS6Q spe-
cifically and especially if the patient has an improvement (reduction) in
192 CHAPTER 11 Review, finishing touches, and closure

symptoms with the cotton in place. A patient with a positive cotton test
might benefit from potential inferior turbinate augmentation procedures.32
3. CT imaging is helpful although not diagnostic for ENS.
4. Computational fluid dynamics (CFD) studies nasal airflow by means of nasal
modeling. There is significant airflow disorganization after “surgical (or
virtual) reduction of the inferior turbinate.”33 This newly disorganized
airflow favors the middle turbinate region instead of the normal inferior
turbinate region.
5. Intranasal trigeminal functional testing: It is now well known and acknowl-
edged that it is the nasal mucosal cooling by the nasal airflow that initiates
signaling through the trigeminal nerve by way of the special receptor,
transient receptor potential melastatin 8 (TRPM8) also known as the
menthol receptor, that signals the presence or absence of ample airflow to
the brain.33 Konstantinidis et al. noted that ENS patients had a substantial
decrease in trigeminal lateralization (menthol) compared to healthy con-
trols.355 In 2012, Scheibe et al. examining normal individuals showed
greater trigeminal sensitization of the nose anteriorly compared to trigem-
inal sensitivity at the posterior part of the nose.358 Additionally, Li et al.
discovered that ENS patients had poorer methanol detection thresholds
compared to those in the healthy control group.43
6. Damage to (or the wholesale removal of) the trigeminal thermoreceptors
(sensory function) such as TRPM8 located in inferior turbinate epithelium
may lead to a subjective sense of nasal airway obstruction, dyspnea, and
possible suffocation.
7. Testing trigeminal function can conceivably be used in diagnosing the ENS
patient. The work of Eccles and Jones illustrated that menthol inhalation
enhances the perception and feeling of an increased nasal airflow by stim-
ulating the trigeminal cold receptors in the nasal mucosa. These effects
occurred without affecting nasal airway resistance or inducing any decon-
gestant effect triggered by the menthol itself.359,360
In summary: the physiopathology of ENS remains poorly elucidated, but several
complementary hypotheses are now found in the literature. ENS may result from
loss of physiological nasal functions (humidification, warming, and cleansing of
inspired air) due to reduced mucosal area74 inducing proportional loss of the sensory,
tactile, and trigeminal thermoreceptors, the temporary receptor potential melastatin
8 (TRPM8) receptors, which are indispensable for physiologically managing inhaled
air and experiencing the sensation of normal breathing.33,47,74,353
Lately, numerous studies assessing nasal airflow using CFD found noteworthy
disordered (disorganized) airflow pattern distribution in ENS patients with differ-
ences in CFD findings between patients after the inferior turbinate resection some
of whom develop ENS others that do not.335,353,361,363 It is thought, by some, that
perhaps at some time in the future CFD studies could be a valuable objective tool
for diagnosing ENS but not at the moment.363
 1. Managing the empty nose syndrome patientdsummary 193

Scheithauer28 demonstrated that ENS was associated with decreased humidifica-

tion, increased warming, and reduced nasal airflow resistance. These functional los-
ses were estimated at around 23% following turbinectomy.74 Several studies clearly
demonstrated that significantly reduced inferior turbinate volume affects nasal cav-
ity airflow.19,55
These airflow changes underlie an alteration of pulmonary function. Nasal resis-
tance plays a major role in opening peripheral bronchioles and optimizing alveolar
ventilation. This in turn improves gas exchange, increases negative thoracic pres-
sure, and enhances cardiac and pulmonary venous return.19 Thus, normal nasal resis-
tance during expiration helps maintain pulmonary volume, indirectly determining
arterial oxygenation.14 These alterations induce the sensation of obstruction reported
by patients, which may go as far as a feeling of suffocation. The paradox between
subjective congestion and reduced nasal resistance is in all likelihood due to
abnormal aerodynamics and “disturbed healing” after inferior turbinate trauma as
suggested by Sozansky and Houser353 and the work of Zhao et al.354 The sensation
of pharyngeal dryness often reported by ENS patients is due to an airflow that is
insufficiently humidified obviously yielding a drying of the airway mucosa.28
ENS is a late complication of turbinectomy varying form months to years before
the functional residual capacity of the nose (FRCn) collapses. Extensive resection
(total or subtotal turbinectomy) incurs the greatest risk, but ENS has also been re-
ported secondary to partial resection, mainly partial inferior turbinectomy involving
the anterior part or head of the turbinate, which plays a major role in internal nasal
valve function.20 Conservative turbinate reduction by turbinoplasty with lateraliza-
tion (out-fracture) is thus recommended after (nasal obstruction resistant to well-
conducted medical treatments in patients with turbinate enlargement [hypertrophy]).
The amount of mucosa resected is not necessarily implicated, and the risk of ENS
cannot presently be predicted; therefore, conservativism is the name of the game.
The risk of developing ENS following turbinate treatments includes mucosal
resection not only to the amount of mucosa removed but also related to an undeter-
mined individual physiological capacity and perhaps environmental factors with es-
timates, in the literature, ranging from 2% to 20% to as high as 35% according to the
type of turbinate surgery that was performed.2,24
It is conjured, no conjectured, speculated that ENS affects “only a few” of the
hundreds of thousands of patients who have undergone one or more endonasal pro-
cedures with the various precipitating underlying factors are only partially under-
stood. One point of contention concerns the frequent association with psychiatric
disorder and possibly psychosomatic pathologies.55,74 A possible role of psycholog-
ical stress in certain patients, as suggested in tinnitus, has been raised.55

1.8 Etiology of ENS

In our view, ENS remains a secondary AR, especially secondary to a total or subtotal
inferior turbinectomy.2e4,18e28,33,73,76,214 Radical turbinate resection must be con-
demned in the absence of disease with malignant potential since many of these
194 CHAPTER 11 Review, finishing touches, and closure

patients that we have diagnosed with ENS have had a radical total or subtotal
removal of an inferior turbinate as a treatment for nasal airway obstruction.
In addition to radical total or subtotal excisional turbinectomy, ENS may also
arise consequent to various other turbinate treatments including: thermal coagula-
tion (electrocautery-mucosal or submucosal), chemo-coagulation, cryosurgery, laser
surgery, radiofrequency ablation, or coblation; we label these non-surgical
Turbinate Reductive Adjunctive Procedure (n-s TRAP). One challenging aspect
of determining an accurate etiology and incidence of ENS is the fact that it may
take many months to years for ENS symptoms to manifest following the inciting
traumatic event; therefore, subsequent to an initial turbinate treatment, patients
require observation for months to years as they may develop ENS at some time in
the future before nasal functional failure is apparent.18
Some rare cases of ENS presented in the literature include one case of *rhinotil-
lexomania and a single case of osteomyelitis after therapeutic turbinate trauma sec-
ondary to radiofrequency turbinoplasty reported in the Norwegian literature.351,352
* Rhinotillexomania is a condition that causes a person to compulsively pick their nose till
they self-harm. Picking your nose is a habit many people are familiar with. However, when it
becomes an obsessive compulsion to pick your nose, it is rhinotillexomania. Definition from
Google.

1.9 Pathophysiology of ENS

The most current (September 2022) and extensive systemized review of the possible
pathophysiologic mechanisms causing ENS was offered by Kanjanawasee et al.335
They studied original laboratory data on the pathophysiology of ENS attempting to
elucidate the precise pathophysiology of ENS. They screened 2476 studies, included
19 studies, 13 case controlled, with 489 adult ENS patients, met their criteria for in-
clusion. They defined, approved, and presented nine pathophysiological subjects
related to ENS. The nine pathophysiologic themes proposed for the etiology of
ENS and examined by Kanjanawasee et al.335 are:
1. Demographics
2. Symptomatology
3. Anatomic features
4. Airflow analysis
5. Mental health
6. Cognitive function
7. Diagnostic testing
8. Olfactory function
9. Mucosal physiology/inmate immunity
Because of Kanjanawasee et al.335 scientific rigor, quality assessment, and
awareness of bias risk, each one of these nine pathophysiological themes are consid-
ered and individually summarized.
 1. Managing the empty nose syndrome patientdsummary 195

1. Demographics: Climatic region had no influence on the quality of life of ENS

patients.
2. Symptomatology: ENS patients had “higher symptom severity, impaired daily
activity, and worse sleep function” than controls and that the ENS symptome
based 6 question questionnaire (ENS6Q) clearly and accurately described ENS
patients. Some studies found higher Sinonasal Outcome Teste22 (SNOT-22)
scores in ENS versus chronic rhinosinusitis (CRS) without nasal polyps, while
some other investigators found similar SNOT-22 scores between CRS patients
and ENS.
3. Anatomic features: They found that the postsurgical inferior turbinate reduction
size was unrelated to ENS symptoms and that the inferior turbinate volume was
similar between patients regardless of ENS symptoms. They found an example
of where 50% of ENS patients (after inferior turbinate reduction) had evidence
of concomitant sinus disease radiologically which is what was also found in the
initial paper by the Mayo team in 2001.18
4. Airflow analysis: They found that nasal resistance and nasal airflow were com-
parable in patients with or without ENS after turbinate reduction.
As expected, the minimum cross-sectional area obtained by acoustic rhinometry
in the ENS group was higher (more space) than controls. Rhinomanometry
calculations (measured air pressure changes divided by airflow changes) were
lower in ENS patients compared to control subjects, again as expected. Using
CFD analysis, when comparing patients with or without ENS after turbinate
reduction, the ENS patients had a decreased (lower) nasal airflow rate at the
lower (inferior) area of the nasal cavity, and while airflow (breathing) shifted
upward toward the region of the middle meatus. Similarly, the wall shear force
distribution (mucosal-airflow interface) was decreased in the ENS group as
compared with the inferior turbinate reduction patient group without ENS and
controls.
5. Mental health: They reported mental health comorbidities in some ENS patients
above 50%, anxiety (73%), depression (71%), and hyperventilation syndrome
(77%). Anxiety, depression, and hyperventilation correlated with ENS symptom
severity.
6. Cognitive function: Functional magnetic resonance imaging (fMRI) was quali-
tatively different in ENS from normal controls. During normal breathing, ENS
patients showed activation in emotional processing areas of the temporal lobe
compared to normal controls.
7. Diagnostic testing: The menthol detection test was impaired in ENS, and cotton
placement in the airway (cotton test) improved (reduced) symptoms in the ENS
population.
8. Olfactory function: Subjective impairment was reported in postturbinate
reduction ENS patients, but quantitative measures were similar to non-ENS
patients.
196 CHAPTER 11 Review, finishing touches, and closure

9. Mucosal physiology/innate immunity: Turbinate histopathology in ENS was

different compared to normal showing a tissue-remodeling pattern. nNO levels
were lower in ENS patients.
Significantly and remarkably, as noted above, Kanjanawasee et al.335 found a
substantial comorbid mental health burden in ENS patients, as we did.18 Interest-
ingly Kanjanawasee et al.335 emphasized the work of Freund et al.74 who observed
that when ENS patients were examined with fMRI, there was a qualitative difference
between ENS patients and normal controls. This may somehow explain the comor-
bid mental health burden seen with ENS patients, as there was activation in the
emotional processing areas of the temporal lobe compared to controls when breath-
ing “normally.”
All in all, Kanjanawasee et al.335 concluded that yes, there is overwhelming ev-
idence of comorbid mental health disorders in ENS patients.
Kanjanawasee et al. trying to understand the ENS patient’s frequent feeling of
nasal congestion with a “wide open nose” noted that since there are no specific
airflow receptors in the nose, it is now known that nasal patency is perceived by
the triggering of the trigeminal cool thermoreceptors (TRPM8) in the nasal
mucosa.335,354,355
The understanding is that normal nasal airflow evaporates H2O from the nasal
epithelial lining, cooling and activating trigeminal transient receptor potential mel-
astatin 8 (TRPM8) receptors which induce neuron depolarization thereby stimu-
lating the respiratory center in the brain. Apparently, menthol, within its cooling
effect also activates these trigeminal cool receptors (TRPM8) and by this mechanism
produces the feeling of an improved breathing without altering any nasal airflow or
changing nasal resistance.47,359 They allowed that a normal trigeminal cool thermo-
receptor response (TRPM8) is present in some ENS patients, but the influence of
“altered airflow and the evidence of surgery as the cause for ENS are unclear.”335
Earlier (2015), Sozansky and Houser in their study and search for the pathophys-
iology explaining ENS concluded that a belief in an anatomic basis for ENS “falls
short” as an adequate explanation for this disorder.353 They recognized that the
typical standard measures of nasal airway obstruction did not correlate with the
feeling of nasal airway obstruction. Recognizing that rhinomanometry, acoustic
rhinometry, and peak nasal inspiratory flow measurements did not “measure” the
physiologic mechanism that senses nasal airway patency, they explored the literature
regarding thermoreceptors and nasal airflow sensation, airflow pattern behavior al-
ternations in normal and in ENS patients along with neurosensory system aberra-
tions all laser focused on understanding dyspnea in ENS, in the presence of a
“wide open airway.” They constructed an understandable explanation of this phe-
nomena as follows: first, pharmacologic modulation of trigeminal afferents has
been shown to alter the perception of nasal airway patency. For example, a topically
applied nasal anesthetic produces a sensation of nasal obstruction, while topically
applied menthol produces a sensation of decongestion (increased breathing) without
altering nasal structural morphology, the anatomy. Concluding that the perception of
 1. Managing the empty nose syndrome patientdsummary 197

nasal airway patency has a neurosensory mechanism, not anatomic. The primary
physiological mechanism causing the sensation of nasal patency is the activation
of trigeminal cool thermoreceptors secondary to the cooling of the nasal mucosa.
The specific trigeminal cool thermoreceptor has been identified as trigeminal ther-
moreceptor transient receptor potential melastatin subtype 8 (TRPM8), a receptor
for menthol.354 Zhao et al. realized that the perception of nasal airway obstruction
has almost no correlation to instruments for measuring nasal airflow obstruction
such as rhinomanometry, acoustic rhinometry, and peak nasal inspiratory flow.
They knew of prior work suggesting that the feeling of nasal airway patency resulted
from trigeminal activation by cool inspiratory airflow.354 As a consequence, they
studied nasal mucosal heat loss in 22 healthy subjects constructing “real-time”
CFD nasal airway models and concluded that:
“These results reveal that our noses are sensing patency via a mechanism
involving localized peak nasal mucosal cooling.”354
Remember, one of the main respiratory functions of the nose is to charge the
inspired air with warmth and moisture (humidification) so that carbon dioxide
(CO2) and oxygen (O2) exchange can occur optimally at the alveolar level. This con-
ditioning of the inspired air is achieved through evaporation of water from the nasal
mucosal epithelial surface. During expiration, a reciprocated reversal occurs, return-
ing warmth and moisture back to the nasal airway mucosa. In other words, the
perception of nasal patency involves activating these trigeminal cold thermorecep-
tors in the nasal mucosa by the cooling effect of nasal inspiratory airflow.
TRPM8 is triggered when “high speed” air enters the nose causing evaporation
(cooling) of nasal mucosal surface fluid (H2O) reducing the membrane fluid level
which in turn fires the TRPM8 receptors causing neuronal depolarization; subse-
quent stimulation of its connections to the respiratory center in the brain. When
the nose is topically anesthetized, the TPMP8 receptors fail to activate; therefore,
the subject feels nasal congestion. Anterior nasal septal deformities, nasal valve ob-
structions, and nasal packing prevent (inhibit) air cooling activation of TRPM8 re-
ceptors; hence, the subject feels congested.
Apparently, the brain perceives a lack of TPMP8 receptor stimulation as the need
to signal apnea, producing an increase in the work of breathing. Anything that hin-
ders the evaporation of nasal mucosal fluid such as thick secretions or even a nasal
septal deformity induces a sense of nasal airway congestion. Another way of
thinking about this is that the feeling of nasal patency, easy breathing, depends on
the cooling of the nasal mucosal surface which in turn activates the trigeminal
cool thermoreceptor TRPM8 receptors. Some of the variables that affect nasal
airflow cooling include nasal surface area, air flow characteristics (air speed,
mucosal contact, and wall shear effects), and the number of trigeminal cool thermo-
receptor TRPM8 receptors available to function normally.
In ENS there is reduced turbinate tissue volume and the disturbed air flow char-
acteristics with reduced wall shear, reduced air speed, reduced normally directed tur-
bulent airflow, reduced mucosal wall contact, reduced activation of trigeminal cool
198 CHAPTER 11 Review, finishing touches, and closure

thermoreceptor TRPM8 with reduced CNS respiratory center stimulation; therefore,

respiratory distress at rest ensues the sense of air hunger, apnea, dyspnea, and
suffocation.
Understanding that the trigeminal nerve, which mediates nasal airflow percep-
tion, has been shown to be appreciably be impaired in patients with ENS.355 Abnor-
malities in neurosensory systems may result after a surgical insult since healing may
not result in full recovery with normal physiologic function; these phenomena may
play a significant role in atypical sensory feelings of ENS patients.355
As mentioned previously, now for emphasis, Freund and coworkers observed that
when an ENS patient breathes room air, there is widespread limbic system activation
seen on fMRI.74 This limbic system activation included the cerebellum, the amyg-
dala, the para-hippocampal gyrus, the caudate/septal nuclei, and the left-sided mid-
dle occipital gyrus.
Because of the difference in brain activation in ENS patients compared to normal
controls, it is thought that this abnormal brain activity may contribute to the subjec-
tive feeling of respiratory distress in ENS patients. It has been adroitly suggested that
since so many ENS patients struggle with dyspnea, air hunger is a significant phys-
ical stress that a breathing preoccupation is an understandable significant emotional
stress leading to a sense of fatigue, irritability, lack of concentration (aprosexia
nasalis), anxiety, and depression.353
Thus, in ENS patients, the inspired air entering the nose fails to stimulate the tri-
geminal cool thermoreceptors, TRPM8 receptors, located in the nasal mucosa; how-
ever, the inspired air still reaches the lungs which activates the slowly adapting
pulmonary stretch receptors (SARs) signaling the brain that adequate respiration
is occurring.339 Nerve growth factor (NGF) is an important protein, located in
both the nasal epithelium and in the submucosal glands of the turbinates. NGF is
critical for the preservation (neuroprotective) and restitution (repair) of both sensory
and sympathetic and sensory neurons.339,357
If the turbinates are grossly resected or if the pseudostratified ciliated mucosal
surface is savagely injured, as seen in aggressive turbinate resection surgery, the neu-
ral connections, during the healing process, are sometimes spoiled or utterly corrup-
ted. As a consequence, these injured corrupted neurons are unable to adequately
carry their electrical messages to their “correct destination” resulting in the feeling
of nasal obstruction. Perhaps it is a ruined postsurgical (post-traumatic) neural re-
covery that answers the question, why some patients develop ENS despite an appar-
ently identical turbinate procedure.
Jennifer Malik and colleagues used CFD studies on five patients with aggressive
inferior turbinate reduction but without ENS symptoms comparing them to 12
symptomatic ENS patients also with previous aggressive inferior turbinate reduc-
tion. Twenty individuals served as healthy controls. Surgical results were established
using the 22-item Sino-Nasal Outcome Test (SNOT-22) Nasal Obstruction Symptom
Evaluation (NOSE) scores Empty Nose Syndrome 6-Item Questionnaire (ENS6Q)
(11 for ENS).361
 1. Managing the empty nose syndrome patientdsummary 199

With the 12 symptomatic ENS patients, they found an airflow imbalance with
reduced wall shear stress inferiorly only little airflow in the inferior regions. These
symptomatic 12 ENS patients also had impaired nasal trigeminal function, as
measured by menthol lateralization detection thresholds (LDTs). On the other
hand, the five patients who had the aggressive inferior turbinate reduction patients
without ENS symptoms, their airflow was directed to the inferior region as is
seen in normal controls.361
They concluded that:
“While turbinate tissue loss is linked with ENS, the degree of ITR that might
distinguish post-operative patient satisfaction in their nasal breathing vs. devel-
opment of ENS symptoms is unclear. Our results suggest that it may be a com-
bination of distorted nasal aerodynamics and loss of mucosal sensory function
potentially lead to ENS symptomology”361
Note: IRT is an abbreviation for inferior turbinate reduction.

1.10 Preventing ENS

Regardless of turbinate treatment strategies advocated by some surgeons, the
optimal turbinate management lies in the prevention of ENS. Preservation of nasal
mucosal and submucosal (lamina propria, stroma) tissue when managing the turbi-
nates helps elude the catastrophic calamity of ENS. Unfortunately, the precise
amount of nasal mucosa and submucosa (lamina propria, stroma) with the rich
vascular supply that must be preserved during intranasal turbinate reduction (modi-
fication) procedures to prevent ENS is presently unknown. We should always mini-
mize turbinate manipulation to preserve mucosal and submucosal functional tissue.
Because the nasal mucosa is the functional entity involved in air conditioning, mini-
mally invasive surgery on the turbinate that preserves the nasal mucosa is key to
achieving optimal results and reducing the risk of developing ENS.
A technique that accomplishes the main goal of widening the nasal passages (for
improved breathing) while preserving the trigeminal cool thermoreceptors (TRPM8
receptors) within the mucosa (for the normal sensation of breathing) and minimizes
excisional and thermal trauma to the submucosal neurovascular bundles will maxi-
mize the chance to avoid ENS.
Does such a technique exist?
As previously presented, Passali et al. in a randomized comparative “technique”
study on 382 patients acquiring results after four and six years showed that the best
long-term results regarding free nasal breathing, quicker recovery of mucociliary
clearance, and normal local IgA secretion was when they performed submucosal,
nonthermal, resection (turbinoplasty) in combination with a lateralization (out-
fracture) of the inferior turbinate.211,216
Prevention largely depends upon “rational” management of the turbinates, mean-
ing lessening inferior and middle turbinate tissue loss by minimizing turbinate
trauma and limiting tissue reduction (removal) or thermal damage during reductive
procedures.
200 CHAPTER 11 Review, finishing touches, and closure

1.10.1 Middle turbinate(s)

Except for inverting papilloma, juvenile angiofibroma and malignancy where exci-
sion of the lateral wall of the nose including the middle turbinate is obligatory plan
on protecting the middle meatus to avoid subsequent frontal sinusitis by saving the
middle turbinate when feasible. This goal may be elusive when the middle turbinate
is partially destroyed by nasal polyps in CRS.

1.10.2 Inferior turbinate(s)

The work of Larrabee and Kacker264 supported Passali et al. as the best approach for
reducing the inferior turbinate.211,216 Conservative turbinate reduction by turbino-
plasty with lateralization (out-fracture) is thus recommended after (nasal obstruction
resistant to well-conducted medical treatments in patients with turbinate enlarge-
ment [hypertrophy]).211,216
With our physiological thinking, any practitioner pursuing inferior turbinate
reduction has the duty, responsibility, and obligation to preserve the pseudostratified
epithelial mucociliary transport system, minimize damage to the submucosal (lam-
ina propria, stroma) neurovascular morphologic structures avoiding adverse physi-
ologic consequences and the resultant sequelae all the while improving the nasal
airway breathing function.
Consequently, “cold-knife” techniques appear to have the edge for now, avoiding
thermal trauma as submucosal vascular choking fibrosis also deprives the overlying
epithelium with the necessary nutrition to maintain a healthy mucociliary transport
system and the secretory deprivation robs the requisite moisture needed to charge the
inspired air with heat and moisture allowing optimal exchange of O2 and CO2 at the
alveolar level.
Prevention of ENS entails turbinate conservation during endonasal surgery
including rhinoplasty, whenever turbinate reduction is considered. Turbinate conser-
vation is fundamental to minimizing the risk of ENS.18 Inferior turbinectomy, in the
past, has been a usual procedure for nasal obstruction in cases of turbinate enlarge-
ment resistant to medical management.28 Nevermore, please.

1.11 Medical treatment of ENS

Regarding diagnosis, we now have two validated diagnostic instruments, the ENS6Q
questionnaire31 and the cotton test.32 With an ENS6Q31 result over >11 and a pos-
itive cotton test32 along with clinical history of previous turbinate surgery and phys-
ical examination, the bed rock of medical evaluation, we are able to relatively
confidently diagnose patients with ENS and initiate medical management. Although
noncodified, medical treatment is obviously indispensable and is the first-line pre-
scription in all cases.
It seems that adequate medical treatments are less effective for ENS patients than
for patients with secondary AR of other etiologies.58
The initial medical approach is focused on controlling crusting, foul odor, pain
(post-traumatic neurogenic pain), and the emotional turmoil requiring psychological
 1. Managing the empty nose syndrome patientdsummary 201

support since, in countless accounts, more than 50% of patients are afflicted with
anxiety and depression.18,33,62,73,74,76,334e349
Offering a summary of the treatment strategies for the ENS, Gill and associates33
opined:
“Nasal humidification, patient education, and treatment of possible concomitant
medical conditions (e.g., depression) constitute first lines of treatment.”33
For the crusting and foul odor, bulb syringe (“power”) lavage with hypertonic
saline is exceptionally helpful.63 Gentamycin 80 mg in a liter of saline (Wilson so-
lution) may also be used as necessary for controlling bacterial overgrowth and the
attendant fetid malodor. Oil of sesame for moisturizing lubrication of the nasal crust-
ing and rose geranium for the foul odor control; both may be topically applied as
desired and have been used for “nasal atrophy” for over a century at the Mayo Clinic.
Pain management (post-traumatic neurogenic “phantom limb syndrome” type of
pain) is challenging and must be managed by skilled experts in pain management.
Recently, from 2019 to 2022, there has been an increased awareness that many
ENS patients have serious emotional pain including depression, anxiety, and suicidal
ideation.33,76,334e349 The initial Mayo paper (2001) documented that 125 of 242
(52%) of the ENS patients were diagnosed with depression by the Minnesota Multi-
phasic Personality Inventory (MMPI) and/or by consultation with a clinic psychia-
trist.18 In an extensive review paper by Kanjanawasee et al.335, more than 50% of
ENS patients were diagnosed with anxiety and depression, while Gill et al.33 re-
ported that 66% of their patients presented with some anxiety and depression, while
patients reported by Kim et al.336 had “depression prevalence of 71%.”
In (2015), a paper published in the psychiatric literature labeled and treated ENS
as a psychological illness: “Treating empty nose syndrome as a somatic symptom
disorder.”346 Lamb et al. in the latest (2022) paper discovered 53% of ENS patients
met the diagnostic criteria for a somatic symptom disorder (SSD).334 In another new
(2022) paper by Huang et al.340 they confirmed that many ENS patents suffer signif-
icant emotional anguish. They studied 62 ENS patients and documented that 43.5%
(27 of 62) had suicidal thoughts (ideation). They concluded that:
“Recognizing individuals who may carry suicidal thoughts and provide appro-
priate psychological interventions is critical to prevent tragedy“340
Doubtless, in addition to the “standard” medical approach to ENS, the new “or-
thodox” medical management, separately but emphatically, includes identifying and
managing the emotional angst many of these ENS patients experience which, when
recognized, know that optimal care is achieved by psychiatrists or psychologists
qualified and skilled in treating anxiety, depression, and expressly dealing with pa-
tients precisely overwhelmed with suicidal ideation. Consultation with these profes-
sionals is at times clearly compulsory to avoid catastrophe, particularly prior to any
planned surgical intervention for ENS.
In summary, the essentials of medical treatment for ENS patients include the
following:
202 CHAPTER 11 Review, finishing touches, and closure

1. Hypertonic saline irrigationsdwith a bulb syringe 3 oz (90 mL) each time of

application or use a powered Waterpik using at least 3 oz (90 mL) of hypertonic
saline two to three times a day to control the dry crusted nasal mucosa. Best in
shower or over a sink. In the morning upon waking-up and before bed. If
additional treatment is needed, a third irrigation can be performed sometime
during the day. This can be homemade; see Table 12
Or you can buy the Neil Med sinus rinse: It should be administered two to three
times a day as a hypertonic saline irrigation (two packets per each adminis-
tration) as noted above. The product can be viewed at the following link: Sinus
Rinse Kit with 50 Packets (neilmed.com). This should be available at most retail
pharmacy locations to purchase over the counter.
2. Wilson’s solution (80 mg Gentamycin in one liter saline)d1 oz (30 mL) is used
two to three times a day to control the dry crusted nasal mucosa. Best in shower
or over a sink. In the morning upon waking-up and before bed. If need addi-
tional treatment, a third irrigation may be performed sometime during the day.
This is obtainable from the Mayo Clinic pharmacy, Rochester, Minnesota Mayo
pharmacy, Contact number: þ1 (507) 284-4041.
3. Oil of sesame with rose geranium
For nasal odor control.
Dispense 50cc.
Apply two sprays each nostril twice daily.
This product has a 90-day expiration.
This is a special proprietary formulation obtainable from the Mayo Clinic
pharmacy, Rochester, Minnesota Mayo pharmacy. Contact number: þ1 (507)
284-4041.
4. *Menthol Inhaler
Adding menthol to local treatments may provide benefit in terms of reducing the
sense of nasal obstruction.74 The menthol product can be viewed at the
following link: Non Medicated Vicks VapoInhaler - Vicks.
It should be available at most retail pharmacy locations to purchase over the
counter.
*Note: “The Vicks VapoInhaler is a convenient non-medicated nasal inhaler formulated
with a proprietary blend of ingredients including menthol and camphor so you can
experience nonmedicated soothing vapors. It’s easy to usedjust inhale he soothing and
refreshing nonmedicated vapors through each nostril and use as often as you need to. It’s
also easy to carrydtake it with you in your purse or pocket so you can discretely enjoy
the soothing nonmedicated vapors you need to make it through the day for adults.
Not recommended for use by children under 12. Nonmedicated.
Not intended to treat cold or flu symptoms.”
5. Induction of rhinitis medicamentosa* may be considered; with topical appli-
cation of nasal decongestants to consciously produce an intended nasal mucosal
rebound phenomenon.
 1. Managing the empty nose syndrome patientdsummary 203

*Ramey JT, Bailen E, Lockey RF. Rhinitis medicamentosa. J Investig Allergol Clin
Immunol. 2006; 16(3):148e155. PMID: 16784007
6. Pain control, for post-traumatic (amputation) neurogenic pain, refer these ENS
patients to a pain management center.
7. Emotional support, for the frequent incidence of emotional comorbidities
including: anxiety, depression, and suicide ideation refer these ENS patients to a
competent psychiatrist or psychologist interested in caring for these patients.
Catastrophically and tragically four of our own ENS patients, not previously
operated by us, but in our care, committed suicide. Consider a pledge to our patients,
for a conscious awareness, in addition to managing their miserable physical symp-
toms, for our requisite identification of the patient’s emotional state of distress so
they have our full attention to deliver determined comprehensive and compassionate
care; that pledge is binding. During follow-up assessments, obviously, track and
chart symptomatic changes, particularly the psychological status, offering the
emotional sustenance, in the ample amounts these patients’ plea, which can be drain-
ing of time and emotion from the physician, probably best tailored to the psychia-
trist’s or psychologist’s office.
Just recently, in 2021, two additional supportive medical strategies, needing
investigation and research evaluation, appeared in the literature that may prove use-
ful in the future, and a third purely investigational research approach is listed below
under C.
A. “Lubricants, moisturizing, cytoprotective agents could restore the perception of
physiological breathing. In this regard, a new multicomponent medical device
seems to be promising, as it contains D-panthenol, hyaluronic acid (HA),
vitamin E, vitamin A, and biotin (Rinocross, DMG, Italy).”
From: La Rosa R, Passali D, Passali GC, Ciprandi G. A practical classification of
the Empty Nose Syndrome. J Biol Regul Homeost Agents. 2021 JaneFeb; 35(1
Suppl. 2):51e54.
B. “D-panthenol is the alcohol analog of pantothenic acid (vitamin B5) and is a
provitamin of B5. In organisms, it is quickly oxidized to pantothenic acid. It is
a viscous, transparent liquid at room temperature. D-panthenol is used as a
moisturizer to improve wound healing in pharmaceutical and cosmetic prod-
ucts. It improves hydration, reduces inflammation, and accelerates mucosal
wounds’ rate of healing. D-panthenol readily penetrates the mucous membranes
(including the intestinal mucosa), quickly oxidized to pantothenic acid. It is also
used in the biosynthesis of coenzyme A, which controls a wide range of
enzymatic reactions. HA is a fundamental component of the connective tissue.
HA can modulate the inflammatory response, cellular proliferation, and
remodeling of the extracellular matrix.”
204 CHAPTER 11 Review, finishing touches, and closure

From: Maiolino L, La Mantia I, Grillo C, Grillo CT, Ciprandi G. Functional

recovery in subjects undergoing nasal surgery: a new therapeutic strategy. J Biol
Regul Homeost Agents. 2021 JaneFeb; 35(1):363e366. https://doi.org/10.
23812/20-600-L. PMID: 33624487
C. Premarin nasal sprays (for investigational research use only) for mucosal
thickening.
Conjugated estrogen (premarin) 25 mg/30 mL nasal spray.
Concentration: 83 mcg/0.1 mL (which is equivalent to one spray).
This product is ordered in 30 mL bottles.
Typical dosing is one to three sprays each nostril once or twice a day.
This product has a 30-day expiration.
This is obtainable from the Mayo Clinic pharmacy. Rochester, Minnesota.
Mayo pharmacy, Contact number: þ1 (507) 284-4041.

1.12 Surgical treatment of ENS

Of course, prevention of ENS by evading “excessive” turbinate reduction remains
fundamental to thwarting iatrogenic ENS, but even unmeasurable “minimal” turbi-
nate therapeutic trauma coupled with the inevitable aging process may eventually
affect an unhappy symptomatic person with florid ENS.
Skillful medical management embraces local topical measures (detailed above)
along with patient education and appropriate referrals for pain management and
evaluation for the concomitant emotional mental health comorbidity using validated
screening questionnaires for anxiety, Generalized Anxiety Disorder (GAD-7), and
by using the Patient Health Questionnaire-9 (PHQ-9) for depression. These
screening tools are important accessories to knowledgeable and compassionate clin-
ical management.
The true incidence of ENS after therapeutic turbinate trauma is unknown,
although with our experience, it seems that it is not as “rare” as some assume,
many patients with ENS are conceivably undiagnosed or misdiagnosed, and the
mighty misery of those ENS stricken is both physical with frequent feelings of pro-
found difficulty breathing with feelings of suffocation, disturbed sleep, and a dis-
tressed sense of well-being linked with the emotional misery of anxiety
depression and suicidal ideation.
Leong (2015) studied surgical results in 128 ENS patients from eight studies
clearly expressing that ENS is a most challenging condition to treat.73 He noted
that surgical implantation of various materials for turbinate reconstruction (creating
a pseudo-turbinate) often resulted in improved (reduction) patient reported symp-
toms, irrespective of the graft or implant material utilized. He indicated that:
“There was insufficient evidence from this review to favor any particular
implant material, although it was observed that Silastic had higher extrusion
rate and that hyaluronic acid gel was resorbed within 12 months.”73
 1. Managing the empty nose syndrome patientdsummary 205

While documenting that no one implant material was superior to any another, he
exhorts that authors should follow their patients and report results longer than just
12 months as not all patients were perfectly improved:
“Clinical response varies between patients; up to 21% may report only marginal
improvement.”73
Merely five years later, Gill et al.33 keenly observed that over the past several
years, there has been renewed interest in understanding and treating ENS, including
surgery. This recent rekindling of interest by the ENT community in ENS is evi-
denced by the fact that from the inception of 2019 to the first of November 2022,
the PubMed database offered 45 citations with the term Empty Nose Syndrome
(ENS) in the title.
With two important papers cited by Gill et al.33 both published in 2017, one by
Velasquez et al.31 who presented a validated empty nose syndrome 6 item question-
naire (ENS6Q) and the second paper described the office cotton test by Thamboo
et al.32 The profession now had standardized screening tools by which to define,
describe, and aid in diagnosing ENS patients. Prior to these two 2017 contributions,
from the Stanford group, description of ENS was inconsistent and dependent upon
past history of turbinate trauma associated with various clinical patient presentations
and physician impressions, the prescription for misdiagnosis, resulting in an incal-
culable number of undiagnosed ENS patients.
Gill et al.33 supported the cautious use of these screening tools emphasizing that
they be used as accessories, adjuncts to making medical decisions. However, they
did think that using the ENS6Q with the cotton test might assist in the identification
of ENS patients who could possibly benefit from turbinate surgical augmentation.33
With the notification by Leong73 of possible marginal surgical results of up to
21% of patients in plain view, any surgical step must be considered cautiously since
the patients’ pain symptoms and feeling of nasal dryness are usually not ameliorated
with any type of surgery, even “successful” surgery. Additionally, abnormalities in
the mucosal neurosensory systems may appear secondary to the surgical therapeutic
turbinate trauma as healing may be incomplete resulting in the atypical sensory feel-
ings that some ENS patients experience.355
Critically, in addition to the screening test questionnaires for anxiety and depres-
sion, a professional psychological evaluation with a competent psychologist or psy-
chiatrist, interested in ENS patients, is mandatory prior to any decision to operate,
given the fact that well over 50% of ENS patients have emotional
comorbidities.18,33,334e349 Anxiety and depression were as high as 66% in one
(2020) study33 and even higher in another (2021) study with depression in 71% of
their ENS patients.336
This emotional suffering is often first experienced years after the initiating ther-
apeutic turbinate trauma that precipitated the launch of ENS in the first place.
Because of the irrefutable evidence of monumental mental health issues in ENS pa-
tients, especially anxiety and depression with suicidal ideation, as high as 43.5%,
psychologic consultation is unequivocally advocated, required, prior to
206 CHAPTER 11 Review, finishing touches, and closure

contemplating any surgical intervention given the potential devastating emotional

impact of an unsuccessful surgery.340
Surgical intercession for these ENS patients, that initial rational is for the “build-
ing or creating” of a “neo-turbinate” or “pseudo-turbinate” structure to provide
increased nasal airway resistance by narrowing the airway with a graft or implant
held securely within a submucosal pocket.58,65
Choice of the “ideal” graft or implant material combines a reduced risk of rejec-
tion and contamination with an adequate restoration and maintenance of bulk vol-
ume to the nasal airway.
These creative turbinate tissue substitutions are with biological grafts or syn-
thetic implants have been the principal strategy for surgical reconstruction of previ-
ously resected tissues. This stratagem is itself unproven as a “cure” for ENS; “tissue
replacement” has nonetheless been used for decades, including conchal cartilage and
rib cartilage grafts placed submucosally along the floor of the nose, on the septum, or
on the lateral wall replacing a partially resected inferior turbinate remnant. These
techniques as “simplified” when residual turbinate tissue remains. Otherwise, the
problem confronting the surgeon is more complex, deciding exactly where to place
the graft or implant in a landmark-less field, a creator’s task.
Currently, the term endonasal microplasty is used interchangeably with inferior
meatus augmentation procedure (IMAP) which is used for describing a reparative
endonasal surgical procedure designed to reduce the volumetric size of the nasal
cavity by submucosal implantation of some graft or implant material to restore
regional inferior turbinate volume.58 The procedure is primarily designed to increase
resistance to nasal airflow, reducing airflow so as to increase warmth and humidity to
the inspired air, and to diverge the inspired airflow from the initial turbinate treat-
ment site toward a healthy or nonoperated area.20 The principle consists in posi-
tioning an implant or graft on the septum, floor, or lateral wall.21,58,67
Surgical therapy for ENS seeks to reestablish turbinate tissue volume (and asso-
ciated nasal aerodynamics and nasal sensation) through the placement of injectable
fillers, allografts, xenografts, cartilage autografts, and/or synthetic materials.
Although the exact pathoetiologic mechanisms for ENS are not well understood,
symptoms of ENS may be improved through the judicious patient workup, coun-
seling, and application of selected medical and surgical treatments.
An assembly of multifarious materials, diverse and varied, including injectable
fillers such as hyaluronic acid gel, carboxymethylcellulose/glycerin gel (Prolaryn),
synthetic implant materials (Plastipore, Medpor, Gore-Tex, Teflon, Silastic sheets,
beta-Tricalcium phosphate, hydroxyapatite and ceramic bioactive glass (Glass-
BONE), allograft materials (Alloderm and Bone Source), and autologous materials
(bone, costal cartilage, platelet-rich fibrin (PRF) with diced conchal cartilage, rib
cartilage, muscle, fat), cadaveric rib cartilage, and even porcine small intestine
submucosa (SIS) xenograft have all been tried and used for surgical reconstruction
of the missing turbinate tissues.19,62,64,72,345,366e373
Although almost all authors claim “good” results meaning reductions of clinical
nasal airway symptoms, without complications, intraoperatively or postoperatively,
 1. Managing the empty nose syndrome patientdsummary 207

along with a reduction of emotional symptoms at or at some time less than one year
after surgery in small published series, but the amount of volume restored by surgery
and their durability and efficacy remain to be determined for the long term, opti-
mally years into the future.19
Regarding pertinent pathophysiology and its relationship to surgery, Hassan
et al.371 suggested that several theories or considerations need inquiry. When turbi-
nate mucosa and submucosa are resected or injured first, there is the loss of sensory,
tactile, and thermal receptors (TRPM8)365 along with a sweeping reduction in the
number of functional neurovascular structures. A recent work, published in Laryn-
goscope, by Wu et al.365 studying the histopathology of 17 ENS patients including
immunohistochemical staining of transient receptor potential melastatin 8 (TRPM8)
with six normal controls. In the ENS patients, they found significant squamous meta-
plasia, increased submucosal fibrosis, fewer submucosal glands, and a “lower
expression level of thermoreceptor-like transient receptor potential channel melasta-
tin 8 (TRPM8).”365
Gill et al. (2020) were aware of these new data suggesting that there is impaired
trigeminal nerve function which may also play a role in the pathophysiology of
ENS.33 As a consequence of all these changes, the reduced number or injured neuro-
vascular structures elicited a decreased humidification, decreased warming, and a
decreased number of trigeminal thermoreceptors (TRPM8), with the ensuing sense
of difficulty breathing, or the inability to experience a normal unobstructed breath-
ing sensation in these ENS patients. Hassan et al.371 let us know that in ENS, the
CNS is being studied which could clarify the patient’s subjective feeling of nasal
airway obstruction as a disturbance of neural mucosal afferent pathways and
impaired intranasal trigeminal function.74,355
Additionally, a reduction (a lessening) of the nasal airway resistance almost al-
ways occurs secondary to gross tissue removal, as anticipated; expected.47 Absent
the head of the inferior turbinate, the nasal resistance is reduced which may be
seen, perceived, by the CNS respiratory center as respiratory distress resulting in
the hyperventilation syndrome in 77% of their studied ENS patients.13,74,358 With
resistance changes, there is an alteration of pulmonary gas exchange as the nasal
resistance plays a vital role in the opening of pulmonary bronchioles and physiolog-
ical alveolar oxygenation as noted by Houser in 2007.19 The next consideration in-
cludes the physical disruption of the nasal airflow, an unbalance between air
distributed (flowing) primarily to the superior nasal cavity in ENS instead of toward
the inferior nasal cavity along the inferior turbinate as submitted by Malik et al.361
Currently, curative and a definitive surgical treatment for ENS is actually
nonexistent.
Despite the current status of surgical results, recently, the Stanford group has
vigorously focused on surgical approaches to relieve these ENS patients of their
onerous symptoms. All these are examples of perturbation theory, a method for
attempting to continuously improve a previously obtained approximate solution to
a given problem.
208 CHAPTER 11 Review, finishing touches, and closure

Thamboo et al. published a 2017 paper establishing the Cotton test as a way of
confirming ENS diagnosis utilizing their validated Empty Nose Syndrome 6-Item
Questionnaire ENS6Q was entitled:
“Defining surgical criteria for empty nose syndrome: validation of the office-
based cotton test and clinical interpretability of the validated empty nose syn-
drome 6-item questionnaire.”32
A few years later, in June 2019 another paper, also from Stanford, by Borchard
et al.366 appeared acknowledging that while augmentation of the inferior meatus has
been previously proposed for ENS patients that efficacy* information with validated
survey forms (questionnaires) was minimal; therefore, they wrote:
“Surgical augmentation of the inferior meatus has been proposed to treat ENS,
although efficacy data with validated, disease-specific questionnaires is limited.
Instead we evaluated submucosal injection of a transient, resorbable filler into
the inferior meatus to favorably alter nasal aerodynamics in ENS patients.”366
*“Efficacy trials use strict inclusion and exclusion criteria to enroll a defined, homogenous
patient population.
Effectiveness studies (also known as pragmatic studies) examine interventions un-
der circumstances that more closely approach real-world practice, with more hetero-
geneous patient populations, less-standardized treatment protocols, and delivery in
routine clinical settings.
From: Singal AG, Higgins PD, Waljee AK. A primer on effectiveness and efficacy
trials. Clin Transl Gastroenterol. 2014 Jan 2; 5(1):e45. https://doi.org/10.1038/ctg.
2013.13. PMID: 24384867.
They anticipated that the submucosal instillation (injection) of carboxymethyl-
cellulose/glycerin gel (Prolaryn) into the inferior meatuses of their 14 patients would
be reabsorbed in a few months. Their results were excellent after three months with
improvements in all their subjective measures including: ENS6Q, 22-item Sino-
Nasal Outcome Test (SNOT-22), Generalized Anxiety Disorder 7-item scale
(GAD-7), and Patient Health Questionnaire-9 (PHQ-9), for depression. They
concluded that:
“Transient, focal airway bulking via submucosal filler injection at sites of infe-
rior turbinate tissue loss markedly benefits ENS patients, suggesting that aber-
rant nasal aerodynamics from inferior turbinate tissue loss contributes to
(potentially reversible) ENS symptoms.”366
In November 2019, Talmadge et al.345 suggested that future office injections of
submucosal absorbable fillers, for “off-label” use, requiring proper informed con-
sent, could possibly be used as a temporary “trial.” Thereby confirming the office
cotton test and determining the patient’s satisfaction with a transient but imperma-
nent improvement (lessening) of their ENS symptoms as the gel filler is resorbed
over a 2e12-month period.345 This would occur prior to installation of any material,
 1. Managing the empty nose syndrome patientdsummary 209

organic or inorganic, graft or implant, as a more “permanent” surgical solution for

ENS sufferers.
Realize that the submucosal injection of “fillers” is not without risk as rare, but
significant problems may occur including thromboembolic complications345 with
tissue necrosis or blindness122 secondary to intravascular injection. In another
2019 offering, this time by Gill et al.76 as an update on ENS disease mechanisms,
diagnostic tools, and treatment tactics they advised:
“Although injectable implants to augment turbinate volume show promise as a
therapeutic surgical technique, there is insufficient data to fully support their
use at this time.”76
Apparently encouraged by the results of the submucosal filler injections with
carboxymethylcellulose/glycerin gel (Prolaryn) at three months, Thamboo, Dhola-
kia, Borchard et al. (2020)367 launched a pilot study in a series of 10 ENS patients
followed for six months with the Empty Nose Syndrome 6-item Questionnaire
(ENS6Q), 22-item Sino-Nasal Outcome Test (SNOT-22), Generalized Anxiety Dis-
order 7-item scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9), for
depression.
They performed 11 procedures on 10 different ENS patients using two different
materials: (1) small intestine submucosa (SIS) grafts for three operations on three
patients and (2) acellular dermal matrix (Alloderm) for eight operations on seven
different ENS patients. They specified that an IMAP has made a considerable differ-
ence for their patients asserting that:
“IMAP can dramatically improve the quality of life of ENS patients regarding
both ENS specific symptoms and psychological wellbeing.”367
With a gathering momentum, one year later, in 2021, Jennifer Malik from Ohio
State University in concert with the Stanford group published a fascinating paper us-
ing CFD with five ENS patients buttressed the idea that an IMAP with costal carti-
lage, for example, is able to stabilize and “normalize nasal air flow patterns” in their
five ENS patients. They stated that an IMAP was able to reduce “ENS symptoms in a
durable manner,” but how these symptomatic improvements occurred was unknown.
After six months of study, they concluded:
“This study supports our prior working hypothesis that disordered vectors of
nasal airflow congregate in the middle meatus contribute to ENS symptoms,
not nasal resistance. Moreover, these data illuminate a paradoxical, but consis-
tent, restoration of nasal airflow to the inferior meatus following the replacement
of turbinate tissue volume in the inferior meatus via IMAP, potentially due to the
Coanda effect.”*368
*The Coanda effect is the action in fluid mechanics whereby a flow along a solid surface tends
to follow the curvature of the surface rather than separating. In other words, it is the tendency
of a fluid jet to stay attached to a convex surface.
210 CHAPTER 11 Review, finishing touches, and closure

They acknowledged their study’s limitations of a small sample size (5 ENS pa-
tients) and its nonexistent control group; however, they intend to continue to inves-
tigate altered airflow distribution and its effect on ENS symptoms.368
In 2021, Sachi Dholakia and colleagues from the Stanford group published a sur-
gical treatment paper using cadaveric rib cartilage performed for 17 ENS patients
followed for 12 months.369
Specifically, the cadaveric rib cartilage was packaged, decellularized, and irradi-
ated which was acquired from Musculoskeletal Tissue Foundation (MTF).369 These
patients were diagnosed as having ENS based on: (1) reported discomfort with nasal
breathing and/or paradoxical nasal obstruction after inferior turbinate reduction, (2)
a positive ENS6Q score of at least 11, and (3) a positive cotton test. The data were
collected preoperatively and at 1, 3, 6, and 12 months postoperatively. They noted
that their prior practice at Stanford included injections of carboxymethylcellulose/
glycerin gel (Prolaryn)366 and other tissues, for the IMAP.367,368 Moreover, with
those procedures, their ENS patients were significantly improved regarding their
anxiety and depression symptoms.366,367 They modified their IMAP methodology
in 2017 for qualms about implant resorption requiring additional surgery with com-
plete conversion from a small intestine submucosa (SIS) graft or acellular dermal
matrix (Alloderm) to cadaveric rib graft, now their preferred treatment technique.
Their assessments included: four validated questionnaires: Empty Nose Syndrome
6-Item Questionnaire (ENS6Q), 22-item Sino-Nasal Outcome Test (SNOT-22),
Generalized Anxiety Disorder 7-Item Scale (GAD-7), and Patient Health
Questionnaire-9 (PHQ-9), for depression. Concluding that:
“IMAP via implant of cadaveric rib cartilage provides significant, long-term
improvements in ENS-specific and general sinonasal symptoms.”369
Some findings of note involved the GAD-7 and PHQ-9 questionnaires as mea-
sures of anxiety and the severity of depression, respectively. Those scores were
reduced but not statistically significant because anxiety and depression were in
the mild ranges for those 17 patients “leaving little room for improvement from a
low starting baseline.” 369 Generally, their patients were clinically improved, and
those results were statistically significant.
Of course, not all symptoms are ameliorated with an IMAP especially since the
TRPM8 receptors, so important for the sense and feeling of normal breathing, are
functionally impaired (or totally removed, excised) in patients with ENS. The evi-
dence for the damaged TRPM8 receptors has been provided by the menthol lateral-
ization test and histopathologic study of the inferior turbinate.360,365,369 Laudably,
their study was the first documented report of symptomatic improvement by means
of validated disease-specific questionnaires in patients suffering with ENS at one
year subsequent to IMAP with cadaver rib implantation.
Understandably, surgery does not restore neurological or mucosal receptor func-
tion, but it was recently shown, (2021), by the combined efforts of the group at Ohio
State University and the Stanford group, that IMAP can improve (normalize) nasal
airflow patterns with CFD modeling.368
 1. Managing the empty nose syndrome patientdsummary 211

Two other new surgical papers (2021) are mentioned for completeness. One by
C.F. Chang 370 using PRF with diced cartilage in two patients with a follow-up at
one year and one by Hassan et al. 371 using Bioglass (GlassBONE), in two patients,
one with AR and one with ENS with limited follow-up of four months. What was
uncommon was the use of a sublabial approach for submucosal placement of the
Bioglass (GlassBONE) implant.
In June 2022, with a marvelous yet brief three page “How I Do It” paper in
Laryngoscope, Michael Chang and colleague372 (from the Stanford group with other
colleagues outside of Stanford) described, in detail with video, the surgical tech-
nique for the IMAP with irradiated cadaveric rib for surgically treating two ENS pa-
tients followed for 12 months. They emphasized that a firm diagnosis of ENS is
required with a minimal ENS6Q score of >11 and positive cotton tests (blinded),
on at least two occasions, where the ENS6Q score increases (improves) by 7 points
on each cotton test study.31,32,372
In another 2022 paper, Hosokawa et al.373 used autologous dermal fat (ADF)
following nine ENS patients for three months. Arguing that using autologous tis-
sues like rib cartilage is an invasive technique with a chest scar; however, by exploit-
ing ADF tissue, which is essentially limitless, a surgeon has as much ADF as desired
for any IMAP chosen. They claimed that their nine ENS patients were significantly
improved as measured by Empty Nose Syndrome 6-Item Questionnaire (ENS6Q);
however, dryness persisted, all this without complications.
Talmadge et al.345 in a November 2019 article in Facial Plastic Surgical Clinics
of North America thought that current data for surgical reconstruction of a new
turbinate (neo-turbinate or pseudo-turbinate) in ENS showed possible favorable
long-term effectiveness.
Despite their optimistic cheerful view, to date, 2022, no long-term results, years
into the future, have appeared in the literature for ENS resembling the published
work of Passali et al. for inferior turbinate treatments for 382 patients which Passali
et al. recounted after four and six years postsurgery.211,216
We think in this current year, 2022, although injectables and various grafts and
implants to augment turbinate volume show promise as a therapeutic surgical tech-
nique, there is still insufficient or long-term data to fully support their use at this
time. What is desirable and needed are well designed, well planned, RCTs, with
objective measures, if possible, and subjective measures of symptomatic improve-
ment, with sufficient numbers, followed years, not merely months, into the future.
All in all, this approach is indispensable and imperative to someday answer the ques-
tions surrounding surgical treatment options and alternatives for our ENS patients.
Nevertheless, a realistic but empathetic approach is required considering that the
current evidence is weak for enduring successful surgical intervention. Realizing
that any given individual clinical response varies between patients, according to
Gill et al., about 20% of patients report only marginal improvement from surgery.33
While these surgical studies and explorations are interesting and encouraging,
they are also difficult to fully assess and implement given their limited numbers
and abbreviated follow-up (often less than a year).19,21,62,64e72,366e373
212 CHAPTER 11 Review, finishing touches, and closure

2. Evidence-based medicinedDavid Sackett, MD

The ideas behind EBM come from David Sackett, MD. EBM is primarily about dis-
covery. Discovery of the best medical evidence, for crafting clinical choices, judg-
ments, and rational therapeutic decisions in the best interest of the patient. The entire
concept of EBM is the distinction between decisions based on hard scientific evi-
dence from well designed and competent RCTs as opposed to decisions based on
expert opinion. RCTs avoid bias and placebo effects and are almost statutory for
intelligently comparing competing medical practices.
Unvalidated care must not be undertaken unless in a structured evidence-based
RCT. The ideal double blind placebo-controlled trial cannot easily be applied to sur-
gical comparisons, but the optimal design of RCTs for surgery must be attempted
nonetheless.274 It is fully understood that without evidence from RCTs, there is
no choice but to rely on your clinical reasoning and experience, yet awareness of
a possible flawed conclusion because of a “placebo effect” must always be kept
in mind.

3. Consolidated standards of reporting trials

The CONSORT statement was developed to promote consistency, clarity, accuracy,
and transparency of reporting of RCTs. In this way, all interested parties, re-
searchers, journal editors, and physicians of the general readership know exactly
how the RCT was performed, with a standardized check list for the authors of trials
to adhere to and for journal editors to demand before the results of RCTs are pub-
lished and disseminated.296,297
More recently, in 2010, the checklist and flow diagram have been updated yet
again and expanded to 25 essential items by the leading authorities Douglas Altman,
David Moher, Kenneth Schulz, and others299,300 with the details located at: www.
consort-statement.org.
Professor Douglas Graham Altman’s quote is so germane to research’s expedi-
tionary quest:
“To maximize the benefit to society, you need to not just do research but do it
well.”
CONSORT requirements are important for clinical investigators to have an accu-
rate repeatable standard guideline to follow for performing valid RCTs of the highest
quality so ultimately practicing physicians and surgeons have proven principles to
follow for effective clinical patient care. Journal editors and peer reviewers should
also demand that those investigators using RCTs follow the CONSORT require-
ments so that the highest quality studies are transparently performed with the
 4. Replacement or reversal of a medical practice 213

most accurate data published for their readership to consider when making clinical
decisions.
Even after a quarter of century of demand for following the CONSORT state-
ment, many do not adhere to those principles in their papers published in our
ENT literature.
Not so long ago, in 2018, the group from McGill University evaluating RCTs in
otolaryngology and adherence to the CONSORT statement concluded that the
reporting of RCTs in top nine ORL-HNS journals and in the top Canadian ORL-
HNS journal is “suboptimal.”301 Recall that PSM can imitate a RCT.303,304

4. Replacement or reversal of a medical practice

Optimally, questionable medical practices are replaced by improvements. Sound im-
provements are based on strong and substantial comparative trials (RCTs) where ad-
vancements overtake dubious previous practices.
Prasad et al. reviewed 2044 original articles and found that 146 (40.2%) of once
verified and validated medical practices were reversed (discontinued), when at first
those practices seemed “rational” when in fact they were ultimately substantiated to
be flawed271
“Reversals included medications, procedures, diagnostic tests, screening tests,
and even monitoring and treatment guiding devices. We were unable to identify
any class of medical practice that did not have some reversal of standard of
care.”271
When medical therapies decline in approval and are no longer practiced, it’s
because they are either replaced or reversed (discontinued).
1. Replacement (superseded) occurs when a practice is exceeded by one that’s
superior (better) in result.
2. Reversal (discontinued) occurs when a practice is stopped because it’s either
unsuccessful or harmful.
The solution to a treatment that was reversed (discontinued) is discovering an
“improvement” by randomized controlled trials (RCTs). Proof requirements remain
compulsory; therefore, the charge of our rhinologic community is to ferret out use-
less or harmful practices, by well-designed RCTs, the soul of EBM, principled “care
research.”
Admonishing the profession, with his dazzlingly provocative paper, John Ioanni-
dis320, from the Departments of Medicine, Health Research and Policy, and Statis-
tics, and Meta-Research Innovation Center at Stanford (METRICS), Stanford
University, asserted that most clinical research is not useful, arguing that clinical
research to be useful must have unbiased pragmatic utility for a patient’s well-
214 CHAPTER 11 Review, finishing touches, and closure

being. After listing a number of “utility features” that must be met for clinical
research to be useful, he concluded that:
“Overall, not only are most research findings false, but, furthermore, most of
the true findings are not useful. Medical interventions should and can result
in huge human benefit. It makes no sense to perform clinical research without
ensuring clinical utility. Reform and improvement are overdue.”320
Accordingly, Ioannidis listed some of the features to consider and questions that
need answering for clinical “care research” to be useful that included the
following:320
Problem base: Is there a health problem that is important enough to fix?
Context: Has prior evidence been systematically assessed to inform the need for
new studies?
Information gain: Is the proposed study large and long enough to be sufficiently
informative?
Pragmatism: Does the research reflect real-life? If it deviates, does it matter?
Patient centeredness: Does the research reflect top patient priorities?
Value: Is the research worth the money?
Feasibility: Can this research be done?
Transparency: Are the methods, data, and analyses verifiable and unbiased?

5. Managing middle turbinate enlargement

For the current moment, in the absence of certainty from RCTs, we champion saving
the middle turbinate for both its physiological function and as a critical anatomical
landmark that is especially helpful for revision surgery in patients with CRS with
polyps. Preservation of the middle turbinate is preferred unless there is a particular
clinical scenario in which it is “sensible” to remove portions of it (“insubstantial-
flimsy” structure, or obstruction to sinus outflow, involved with polys or tumors).
In managing a concha bullosa, we favor instrument collapse minimizing airway
obstruction while maintaining both the medial and lateral mucosal surfaces of the
middle turbinate structure since mucocele is rare. Future well-planned RCTs are
required for answering these questions.
Houser (2006) described a case of ENS after left middle turbinate resection as
part of functional endoscopic sinus surgery (CT scan in evidence) with the right mid-
dle turbinate untouched with both inferior turbinates in situ.20 Houser’s report and
our experiences are identical as we have seen patients with ENS secondary to middle
turbinate resection with both inferior turbinates in situ.18
 6. Managing inferior turbinate enlargement (“hypertrophy”) 215

6. Managing inferior turbinate enlargement (“hypertrophy”)

6.1 Evidence-basedproposals
In the realm of medical management of inferior turbinate enlargement (“hypertro-
phy”), various treatments recommended and applied included: steroids (systemic
and topical), decongestants, (systemic and topical), antihistamines, and immuno-
therapy. Patients who “failed” the obligatory three-month trial of medical manage-
ment are candidates for surgical intervention. Principally, there are two types of
“surgical” procedures for inferior turbinate reduction:
Type 1: Transmucosal (transepithelial) approach with epithelial mucosal
destruction.
Type 2: Submucosal (turbinoplasty, turbinate reduction) approach with epithe-
lial mucosal preservation.
The nasal mucosa (epithelium and submucosa) is composed of two distinctive
strata: Fig. 5.2.
1. Epithelium is actually the outer epithelial layer and is composed of pseudos-
tratified ciliated columnar epithelium.
2. Submucosa is called the lamina propria or deeper stromal layer located beneath
the epithelial layer.
An esteemed judgment regarding inferior turbinate surgery was offered by Hol
and Huizing, with the aim of reducing inferior turbinate enlargement (“hypertro-
phy”) reducing nasal airway obstruction, thereby improving nasal breathing.25
“In our opinion, the purpose of surgically reducing the inferior turbinates should
be to diminish complaints of airway obstruction, to improve breathing, all the
while preserving function.”25
They concluded the obvious, that turbinectomy (total and subtotal), electrocau-
tery, chemocautery, cryosurgery, and laser (surface) surgery are all transmucosal
(epithelial) approaches and should not be used, since they are too destructive.25
Therefore, they favored intraturbinal turbinate reduction (turbinoplasty) as the
method of choice.
Specifically, as previously written, surgery is: the medical practice of managing
diseases, deformities, and injuries by actually “cutting” into a part of the body,
while, on the other hand, electrocautery, chemocautery, lasers, radiofrequency,
coblation, or ultrasound are not surgery in the traditional sense of cold-knife “cut-
ting” but nonetheless they are currently considered “surgery” by some authors,
but we choose to call these practices the n-s TRAPs.
With evidenced-based treatment proposals in mind, Larrabee and Kacker264 reviewed
five studies that they rated as level 1 evidence (prospective and randomized trials). These
include the following notable evidence-based treatment contributions.26,27,211,230,235
216 CHAPTER 11 Review, finishing touches, and closure

1. Passàli et al. wrote “Treatment of inferior turbinate hypertrophy: a randomized

clinical trial” in 2003.211
2. Nease et al. wrote “Radiofrequency treatment of turbinate hypertrophy: a ran-
domized, blinded, placebo-controlled clinical trial” in 2004.26
3. Liu et al. wrote “Microdebrider-assisted versus radiofrequency-assisted inferior
turbinoplasy” in 2009.235
4. Cingi et al. wrote “Microdebrider-assisted versus radiofrequency-assisted infe-
rior turbinoplasty: A prospective study with objective and subjective outcome
measures” in 2010230
5. Gindros et al. wrote “Comparison of ultrasound turbinate reduction, radio-
frequency tissue ablation and submucosal cauterization in inferior turbinate
hypertrophy” in 2010.27
Therefore, to date (2022), the evidence-based treatment proposals for “surgical”
management of the inferior turbinate(s) are based on five RCTs,26,27,211,230,235 but
the one favored by Larrabee and Kacker264 was the admirable approach presented
by Passali et al.211,218 Passali and colleagues (1999, 2003) reported on the random-
ized outcomes for all their adult patients (n ¼ 382) having nasal airway obstruction,
secondary to inferior turbinate enlargement (“hypertrophy”) who were refractory
(“failed”) to medical management. These patients were treated with various “surgi-
cal” procedures with the number of patients for each different procedure placed in
parentheses as follows: electrocautery,62 cryotherapy,58 laser cautery,54 submucosal
resection without lateral displacement-out-fracture,69 submucosal resection with
lateral displacement,94 and turbinectomy.45 They performed objective testing
including rhinomanometry and acoustic rhinometry plus measuring the mucociliary
transport times and measured levels of secretory immunoglobulin A.211,218
And in their words:
“These data indicate that submucosal resection with lateral displacement of the
inferior turbinate results in the greatest increases in airflow and nasal respira-
tory function with the lowest risk of long-term complications.”211(Bold italics
added)
They also said:
“After 6 years, only submucosal resection resulted in optimal long-term
normalization of nasal patency and in restoration of mucociliary clearance
and local secretory IgA production to a physiological level with few postopera-
tive complications (p < .001)”211
After studying and following their 382 patients for four and six years, Passali and
associates recommended, as the first-choice technique for treating nasal obstruction
due to inferior turbinate hypertrophy, inferior turbinate submucosal resection (turbi-
noplasty) combined with out-fracture (lateral displacement).211,216
The older “orthodox” techniques include: turbinectomy or subtotal (partial) tur-
binectomy, electrocautery, laser cautery, cryotherapy, submucosal resection, and
 6. Managing inferior turbinate enlargement (“hypertrophy”) 217

submucosal resection with lateral displacement. The newer “modern” procedures

included radiofrequency-assisted turbinoplasty, coblation-assisted turbinoplasty,
microdebrider-assisted turbinoplasty, and ultrasound turbinate reduction. Individu-
ally both microdebrider-assisted and ultrasound turbinate reduction (turbinoplasty)
are especially effective in reducing inferior turbinate size; however, to date, 2022,
a prospective RCT comparing the microdebrider-assisted turbinoplasty with ultra-
sound turbinoplasty has yet to be performed; accordingly, for now, the
microdebrider-assisted turbinoplasty (turbinate submucosal reduction) technique
is the technique of choice since the microdebrider has well-known fluency (turbinate
reduction).
Surgeons should make every effort to preserve the pseudostratified epithelial
mucociliary transport system, minimize damage to the submucosal (lamina propria,
stroma) neurovascular morphologic structures, thereby avoiding the adverse physi-
ologic consequences and the resultant sequelae all the while improving the nasal
airway breathing (respiratory) function.
Based on physiological thinking, surgeons operating to reduce the inferior turbi-
nate have the responsibility to preserve the pseudostratified epithelial mucociliary
transport system, minimize damage to the submucosal (lamina propria, stroma) neu-
rovascular morphologic structures avoiding adverse physiologic consequences and
the resultant sequelae all the while improving the nasal airway breathing function.
Therefore, as suggested by Neri et al.256 Gindros et al.,257 and Berger et al258,259
with their histologic studies that “cold-knife” techniques appear to have the edge
for now, by avoiding thermal trauma as submucosal vascular choking fibrosis also
deprives the overlying epithelium with the necessary nutrition to maintain a healthy
mucociliary transport system and the secretory deprivation robs the requisite mois-
ture needed to charge the inspired air with heat and moisture allowing optimal ex-
change of O2 and CO2 at the alveolar level256e259 With that said, Gindros et al.257
noted after ultrasound treatment some patients had normally organized ciliated
columnar cells in the epithelium suggesting that anatomical and functional restora-
tion of the nasal physiology is possible.
For the future, well-planned evidence-based RCTs are indispensable and imper-
ative to answer “all” pressing questions. We believe that in well-designed and well-
performed RCTs, blinding is possible for surgical and procedural studies when the
operator remains “silent” as to his/her specific involvement with subjective and
objective outcome studies performed by blinded (coded study) evaluators. But until
then, we think that it is the randomized controlled report of Passali et al., followed
for six years, that is the first-choice technique for treating nasal obstruction due to
inferior turbinate enlargement (“hypertrophy”) which is inferior turbinate submuco-
sal resection, turbinoplasty, either with a “cold knife” or with a microdebrider-
assisted turbinoplasty combined with out-fracture (lateral displacement), the
microdebrider-assisted turbinoplasty that is the technique of choice since the micro-
debrider has well-known fluency.
218 CHAPTER 11 Review, finishing touches, and closure

7. Regarding children
Regarding children, we believe that surgeons operating on the turbinates of children
have an explicit moral and ethical obligation to follow, report, and publish on the
trajectory of these children as they passage into adulthood. After serious study
and rightful reflection regarding turbinate surgery in children, Leong, Kubba, and
White322 concluded:
“There is currently little evidence to support turbinate reduction surgery in
children. The role of surgery, if any, has not been properly examined. Further-
more, the long-term effects on nasal airflow dynamics, nasal physiology and
long-term complications remain to be studied.”322 (Bold italics added)
Until well-executed pediatric RCTs are available, Leong et at.322 cautioned the
profession with instructions:
“Do not remove turbinates in children, since there is little evidence to support
turbinate reduction surgery in childhood.”322 (Bold italics added)
Nine years later in 2019, a group from Boston, Massachusetts, compared
different pediatric surgical methods (turbinectomy, electrocautery, lasers, submu-
cous microdebridement, and radiofrequency) for managing pediatric inferior turbi-
nate hypertrophy in 1012 children.323 After a comprehensive literature review, these
authors acknowledged that surgery in children is an “escalation” in the management
of inferior turbinate “hypertrophy.” On the other hand, being ethically honest, these
authors also acknowledged that:
“Still, no guidelines currently exist to help guide the escalation of management
in children.”323 (Bold italics added)
Total inferior turbinectomy for inferior turbinate enlargement (“hypertrophy”)
has been condemned by a number of surgeons and baptized a nasal crime by two
European academic authors, Huizing and de Groot, from the Netherlands, with
whom we are totally in agreement.3,4
We state unequivocally that total inferior turbinectomy for inferior turbinate
enlargement (“hypertrophy”) is a nasal crime, especially in children without the
benefit of a well-designed RCT or without future follow-up into adult years.
Consider, that the primary purpose for inferior turbinate surgery is to reduce
nasal airway obstruction (improve breathing), while preserving nasal function.
Because guidelines from quality RCTs are presently nonexistent (for children), sub-
mucosal resection (microdebrider-submucosal) inferior turbinoplasty (without bony
resection unless conchal enlargement) with out-fracture (lateralization) makes the
most rational current conservative surgical alternative, after failed medical therapy;
suggested by Argenbright et al.328 for children; reinforced by Passali et al.211 pro-
spective randomized trial in adults with six-year follow-up with objective and sub-
jective evaluations. Performing an adequate inferior turbinate out-fracture
 8. Summary, future directions, and closing thoughts 219

(lateralization), the nasal airway can be effectively enlarged and maintained (dura-
ble) for a “prolonged” period (time).211,244e248,250,252
Once yet again, we emphasize that ideally, all our clinical decisions should be
based on EBM and the RCT. What’s a surgeon to do, when trial data of an RCT
is just not available or limited, incomplete, inconclusive, conflicting, or starkly
nonexistent? We think there is no choice but to rely on your clinical reasoning,
the rationalism of “clinical judgment,” yet always aware of a possible flawed conclu-
sion because of “placebo effects.”180
And to reiterate, to establish concrete pediatric guidelines for inferior turbinate
reduction, the profession needs principled “care research” meaning: well-designed
RCTs; with sufficient numbers, objective and subjective outcome measures, fol-
lowed into adulthood. Someday.

8. Summary, future directions, and closing thoughts

8.1 Summary
8.1.1 Definition
Defined, empty nose syndrome (ENS) is a clinical entity without a mutually agreed
upon definition; however, most consider ENS as a complication of radical inferior
turbinectomy or may also result from “lesser” inferior turbinate procedures although
it has also been seen after middle turbinectomy alone.18,20 The exact incidence is
unknown; yet, Chhabra and Houser estimated a rate of 20% following inferior turbi-
nate resection, which produces an “ordinary” dry nose in many patients.19,21 Moore
et al.2 from the University of Nebraska Medical Center reported an incidence of “.
at least 35% of the original 40 patients who underwent total inferior turbinectomy
would be suffering unacceptable nasal symptoms at this time.” The symptomatic
manifestations of ENS occurred between three and five years after the turbinate exci-
sion surgery in their study.2 It is to be distinguished from primary AR (ozena) dis-
playing similar symptomatology. With our experience of personally caring for more
than 300 ENS patients, we emphasize the need for conservative surgical interven-
tion when treating inferior turbinate enlargement (“hypertrophy”) thus avoiding,
preventing, the suffering of ENS by our patients. Preventing ENS is the most impor-
tant strategy when managing the turbinates.21 Surely include middle turbinate pres-
ervation whenever possible and favor the most conservative techniques for reducing
the inferior turbinates to improve breathing as suggested by Passali et al.211

8.1.2 Symptoms
The most common and characteristic-presenting subjective symptom is a sensation
of nasal airway obstruction difficulty breathing, often associated with dyspnea
(breathlessness), the so-called paradoxical nasal obstruction with a sense of suffoca-
tion despite a “wide open” nasal airway.18,19e21,55,347
220 CHAPTER 11 Review, finishing touches, and closure

Associated symptoms include a feeling of an empty nose or lack of nasal airflow

sensation, nasal and pharyngeal dryness, crusting, epistaxis, difficulty falling asleep,
disturbed ability to concentrate (aprosexia nasalis), hypersensitivity to cold air, hy-
perventilation, nasal pain, headaches, hyposmia, generalized fatigue, restlessness, ir-
ritability, and sweeping sense of a disturbed well-being.21,55,58,64 Symptom intensity
varies but may restrict everyday activity.21 Do not discount the emotional toll and
related symptoms experienced by our ENS patients as the incidence of this affliction
is astonishingly high, over 50% in most studies, with anxiety, depression, and sui-
cidal ideation (about 40% in one study) are the usual; a surprising
comorbidity.18,20,33,62,73,74,76,334e350

8.1.3 Diagnosis and diagnostics

Today, ENS is more easily diagnosed when a high index of suspicion is coupled with
a history of previous inferior turbinate surgery sometimes months to years after that
nasal surgery, although middle turbinate trauma may also be associated with
ENS.18,20 The diagnosis is primarily clinical; based on the patient’s reported subjec-
tive symptoms with a nasal cavity that is usually enlarged, meaning that normal
intranasal structures are absent, or reduced, truncated in most instances.

8.1.4 Physical examination

Examination with or without endoscopy often finds the intranasal cavities enlarged
secondary to the previous surgery, with turbinate structures missing or greatly
reduced in volume (size). The nasal mucosa is generally pale, dry (often crusted),
and is easily confirmed on examination.55

8.1.5 Validated diagnostic instruments

Two validated diagnostic instruments are available, one a questionnaire for ENS, the
Empty Nose Syndrome 6-Item Questionnaire (ENS6Q)31 and the cotton test.19,21,32
With a positive cotton test and an ENS 6Q result over >11, the diagnosis of ENS is
sturdily supported.32 With the cotton test, a piece (plug) of moist cotton is placed
intranasally at the estimated site of the head of inferior turbinate before it was
removed. After an interval of 20e30 min, symptom reduction confirmed by repeat
ENS6Q “confirms” diagnosis and suggests that surgical repair may be beneficial.

8.1.6 Imaging
Imaging, while the diagnosis is fundamentally clinical, but suggestive signs may be
found on imaging. The direct coronal CT findings are variable and can range from an
absence of intranasal structures, the nose is empty, devoid of intranasal structures, to
sinus mucosal thickening and maxillary sinus opacity in about 50% of cases18,24,58
(Fig. 1.2).

8.1.7 Mental health

Evidence of comorbid mental health symptoms are seen on the self-rated question-
naires: Beck anxiety inventory (BAI), Beck depression inventory, updated version,
 8. Summary, future directions, and closing thoughts 221

(BDI-II) with Generalized anxiety disorder (GAD-7), and the Patient health ques-
tionnaire (PHQ-9) of depression which can be helpful diagnostically. Neuropsycho-
logical involvement is suggested by fMRI studies that demonstrated specific
activation patterns in temporal and cerebellar regions and in the amygdala of ENS
patients.74

8.1.8 Other tests

Gill et al. (2020) concluded that CT scans, CFD, and intranasal trigeminal nerve
function testing currently have insufficient evidence to support routine use in the
workup of ENS.33 Rhinomanometry and acoustic rhinometry are definitely not diag-
nostic but generally confirms a wider nose with a reduced nasal airway
resistance.19,335,345,353 We use a modified Sumner olfactory test which is suggestive
but not diagnostic for ENS.147 The menthol detection test lower (reduced) in patients
with ENS.43,335,358,359 Low nNO levels are usually seen in ENS.344

8.1.9 Pathophysiology
Understanding the underlying pathophysiology is elusive, but probably involves a
combination of distorted nasal aerodynamics, determined by CFD and disturbed
(distorted) nasal mucosal sensory function with altered (reduced) trigeminal cool
thermoreceptors, TRPM8 receptor, activation which depends on turbulent airflow
with adequate mucosal cooling that does not materialize in ENS, that failure poten-
tially leads to the complex respiratory symptoms of ENS namely dyspnea and
conceivably suffocation.354,365

8.1.10 Management
Managing the suffering ENS patient is challenging diagnostically, additionally
requiring compassionate empathetic emotional wariness. The first and primary track
of treatment is medical, which involves topical lavage alongside psychological sup-
port, often requiring referral to a psychiatrist or psychologist because of the high
incidence of over 50% (in many studies), of anxiety, depression, and suicidal
ideation.18,21,33,62,334e349

8.2 Medical management

After diagnosis, first implement the full gamut of medical stratagems including:
nasal hygiene by lavage with hypertonic saline and Wilson’s solution (80 mg Gen-
tamycin), for humidification, crust, and odor control with oil of sesame and rose
geranium. Trials menthol inhalers for symptomatic relief can be effective. The in-
duction of rhinitis medicamentosa may be considered, with the topical application
of nasal decongestants. Referrals for pain control overseen by competent specialists
in pain management and professional emotional support by a competent psychiatrist
or psychologist is critical given the enormous incidence (over 50%) of anxiety and
depression, some with suicide ideation.
222 CHAPTER 11 Review, finishing touches, and closure

8.3 Surgical management

Surgery is reserved for the most severe cases; whatever the technique, surgery aims
at partial filling of the nasal airway, IMAPs also called an endonasal microplasty.
Understandably, surgery does not restore neurological or mucosal receptor function
or offer pain relief, but surgery may possibly improve (normalize) nasal airflow pat-
terns as shown with CFD modeling.368
Additionally, as reported above, but repeated for emphasis, a pilot study (2020),
with 10 patients followed six months, ENS patients were surgically treated with an
IMAP using SIS grafts in three patients and acellular dermal matrix (Alloderm) in
seven patients. The authors published in the March edition of Otolaryngology
Head Neck Surgery indicating that:
“IMAP can dramatically improve the quality of life of ENS patients regarding
both ENS specific symptoms and psychological wellbeing.”367
While published surgical studies can be interesting and inspiring, they are diffi-
cult to fully assess and implement given their limited numbers and abbreviated
follow-up (often less than a year).19,21,62,64e72,366e373 Unfortunately, without
compelling extensive data from any controlled trials, currently there are no definitive
curative or restorative surgical therapies for ENS; today, there are only promises,
possibilities for the future.

8.4 Future directions

8.4.1 Surgical trials for ENS
For a respectful historical perspective, homage to those before us, let’s remember
that Professor Maurice H. Cottle, MD (1898e1982) of Chicago used the idea of a
“nasal cavity narrowing,” a “nose reducing,” or “smalling” operation for treating
nasal atrophy, in the mid-20th century.374 Today these “narrowing operations” are
regularly termed an endonasal microplasty or an IMAP.
Cottle credited Lautenschläger’s paper (1917) which recognized the benefits of
narrowing the nose in patients with atrophy.*
*Lautenschläger, A.: Ueber die Technik der operativen Ozaenabenhandlung, Berlin klin.
Wchnschr. 54:687, 1917.
After Lautenschläger, there were numerous modifications published by
numerous surgeons using numerous materials placed primarily in submucosal
pockets on the nasal floor, lateral wall, and nasal septum. Our ancestral surgeons,
went, as they say, “polynomial in materials” ranging from: paraffin, starting the
era of implants, celluloid, gutta percha (coagulated latex obtain from trees resem-
bling rubber), fat, rib, cartilage, fascia, bone, ivory, acrylic resins, placenta, polyeth-
ylene and vinyl alcohol sponge, macerated spongy beef and bovine cartilage, as
preambles.
When Dr. Cottle was confronted with a patient with an extremely pale (compro-
mised blood supply) atrophic mucosal nasal floor, he suggested a staged elevation
with immediate replacement of the mucosal flap without grafting or implanting of
any materials at all. This first stage surgical elevation would theoretically increase
 8. Summary, future directions, and closing thoughts 223

the blood supply, thickening the mucosa, allowing for a second stage submucosal
grafting at some later date, ideally avoiding extrusion due to a healthier “thicker”
more vascularized mucosal covering.374
For him, initial treatment was always medical including lavage, corticosteroids,
dietary control, vitamins, vasodilators, and antibiotics. Cottle used lobular, upper
lateral cartilage, and lateral osteotomies as narrowing procedures along with the sub-
mucosal implantation of various materials including polyethylene pellets, polyvinyl
plastic sponge (which ultimately extruded), cancellous bone (which absorbed),
bovine cartilage, and preserved rib cartilage often using an alar facial incision to ac-
cess the lateral nasal wall for the submucosal implantation.
He suggested that these procedures could be repeated as many times as necessary
as long as they were safe and effective (useful), with patient determined tangible
benefits, and he clearly recognized and cited the emotional benefits from these pro-
cedures. Usually the “redo” operation can be performed within a time frame interval
ranging from 10 to 20 months for five to ten years. Affirming that:
“Clinical, social, and emotional rehabilitation can be accomplished and it is
most gratefully received.”374
Back to the future, in 2022, we presently reason, although injectables and various
grafts and implants to augment turbinate volume show promise as a therapeutic sur-
gical technique, there are still insufficient data to fully support their use at this time.
Nonetheless, as Talmadge et al.345 previously suggested, that future office injections
of submucosal absorbable fillers, “off-label” use requiring proper informed consent,
could possibly be used as a temporary “trial.”
That said, it may be reasonable to practice repeated injections of submucosal
absorbable fillers for “off-label” use as long as they are in a “care research” protocol
and is eventually proven to be both safe and effective in ameliorating the symptoms
of ENS. At that future moment, it may become a “standard of care” treatment for
ENS, namely “repeated intermittent injections” of submucosal absorbable fillers un-
til the arrival of stem cell research. The reprogramming of adult somatic cells to
become inducible pluripotent stem cells (iPS cells), has and continues to create
the ability to produce boundless amounts of any type of human tissue cells that
generate complete organs, such as an entirely normal turbinate. This may occur
by seeding the area of absent or damaged turbinate tissue with iPS cells to enhance
and promote the development of an organoid (the process whereby stem cells can
recapitulate a human organ, such as a turbinate). Presto cure, shazam!
What to do?
Our ethical responsibility, when considering “new” innovative procedures or
“reevaluations” of current procedures is to institute authorized “care research” trials.
The purpose is to potentiate possible benefits while curbing adverse effects by
following all the criteria, for bias elimination (placebo control), after the CONSORT
statement for reporting RCTs, to avoid publishing flawed studies with conclusions
that need future reversal.4,44 The ethics of using placebos must be considered along
with the distinction and differentiation between research and care as in surgical
research trials and surgical clinical care. The updated (2010) CONSORT checklist
is located at: www.consort-statement.org.
224 CHAPTER 11 Review, finishing touches, and closure

For surgery, Agha et al.45 stated that CONSORT requirements are necessary
when reporting RCTs:
“There is a clear need to ensure that medical research, especially relating to clin-
ical interventions, is carried out and reported to the highest possible
standards.”45
Should we practice unproven, unvalidated procedures on unwary patients pre-
sented as appropriate certified clinical care? Never!!!
Future well-planned RCTs are indispensable and imperative to answer the ques-
tions surrounding surgical treatment options and alternatives for our ENS patients.
Nevertheless, a realistic but empathetic approach is required considering that the
current evidence is weak for enduring successful surgical intervention for our
ENS patients. Realizing that a given clinical response varies between patients and
about 20% of patients report only marginal improvement from surgery.33
Darsaut and Raymond (2021) emphasized that our ethical medical care credo is
based on reliable, repeatable interventions with proven outcomes, essentially
EBM.38 With uncertainty, Darsaut and Raymond argue that medical ethics demand
that a clear distinction be made between “research” and “care.” That a “separation”
between the two is intended to protect patients from “research” studies designed pri-
marily for some distant patient in some distant future. Practicing moral medicine
within the context of uncertainty was their main concern; therefore, a distinction
was made between validated care and promising unvalidated care offered within
a clearly announced pragmatic “care research” design anticipated to: “act in the
best medical interest of the patient.”38
To establish concrete guidelines for restorative surgery for our ENS patients, we
argue that the profession needs principled “care research.”
What does principled “care research” mean?
We think for ENS that means patients be informed that this is “care research.”
Research in a well-conceived, well-designed, institutionally (preferably) approved
RCT, with sufficient numbers, which may be difficult given the “rarity” of ENS,
ideally with objective diagnostic and outcome measures, if ever possible, as there
are currently no available agreed upon objective diagnostic methods for ENS, and
subjective outcome measures, which are available with the Empty Nose Syndrome
6 question questionnaire (ENS6Q), Sino-Nasal Outcome Test-20 for the assessment
of Empty Nose Syndrome (SNOT-20), the Generalized Anxiety Disorder
questionnaire-7 (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) for
depression. It is also required that these operated ENS patients be followed and re-
ported to the community in the literature years into the future.
The doctor’s dilemma develops when data from RCTs are unavailable since “the
crucial study” was never performed. Ideally, all clinical decisions should be built on
EBM with RCTs, but when RCT data are incomplete or nonexistent, there is no
choice but to rely on “clinical judgment”; ever mindful that erroneous conclusions
may ensue.180 The argument of empiricism (evidence first) versus rationalism (clin-
ical judgment) takes center stage especially when data from a “definitive” RCT are
 8. Summary, future directions, and closing thoughts 225

“limited, incomplete, inconclusive, conflicting, or starkly nonexistent” as it is for

surgical treatment for ENS. When empirical data are unavailable, then experience
and clinical judgment take over as the indispensable alternative.
Remember that Prasad et al. found that 146 (40.2%) of once verified and “vali-
dated” medical practices were reversed, when at first those practices seemed
“rational” and “logical” when in fact they were ultimately proven to be flawed, use-
less, or harmful.271
All in all, proof requirements remain compulsory, to ferret out useless or harmful
practices, by well-designed RCTs, the soul of EBM.
Altogether, studies need the great equalizer, the final arbitrator, “Father Time,” to
“weigh in” before making a “final” adjudication regarding our interventions. Dura-
tion after treatment matters before a “final” therapeutic result can be determined and
“final” proclamation for therapeutic recommendation. Early favorable results may
be short-lived, short-term, transitory with a number of representative examples
known in our field flashing caution.
For instance, contemplate, as presented by Passali et al., that while coblation and
radiofrequency improved nasal breathing in patients with enlarged (“hypertrophic”)
inferior turbinates “briefly,” the effectiveness decreased at three years.240 In 1985,
years prior to labeling ENS, Moore et al.2 found an overwhelming majority of pa-
tients, 35% of 40 patients, at three to five years following bilateral total inferior tur-
binectomy had symptoms consistent with ENS. In the exact same cohort of 40
patients, seen at the first two years following initial surgery, very few patients had
symptoms suggestive of ENS only to become florid with the passage of time.2 As
previously indicated, these findings led their team to denounce total inferior turbi-
nectomy, warning the profession that symptoms may not become obvious pending
the passage of years following the initial bilateral total inferior turbinectomy.2 His-
torically, with our ENS patients, there are past accounts of graft resorption, infec-
tions with necrosis, implant rejection, extrusion, some small sample-sized studies,
some lacking a control group, the full tour of less than optimal reports drawn
from the literature.
With time interval, length of follow up interval in mind, the 2016 work of Pelen
and associates while praiseworthy comparing the “cold-knife” microdebrider reduc-
tion with radiofrequency ablation concluded that both techniques were minimally
invasive and could reliably provide an improved nasal airway subjectively and
objectively assessed as statistically significant without any disruption of nasal phys-
iology.260 The only issue of concern and disquiet was one of duration. Their post-
treatment follow-up was, in their own words:
“Nasal obstruction, the grade of turbinate hypertrophy and other symptoms were
evaluated with subjective nasal obstruction scale and anterior rhinoscopy before
the operation, and three days, seven days, four weeks, and eight weeks after the
surgical intervention.”260 (Bold italics added)
226 CHAPTER 11 Review, finishing touches, and closure

Certainly, projecting the “long-term” effects of a given procedure based on re-

sults after eight weeks of treatment results is a startling speculative leap of faith,
for “who knows” where that leap will land you?
Passali et al. set the standard by reporting outcomes at four and six years of their
382 randomized patients after treating their inferior turbinate enlargement (“hyper-
trophy”) with various therapeutic methodologies.211,216
Pilot studies may be laudable with a brief follow-up of less than a year but for
convincing “long-term” results we need examination and analysis somewhere be-
tween four to six years al la Passali et al.211,216 Perhaps three to five years also seems
a rational and commonsensical duration of time interval between the surgical inter-
vention and the long-term follow-up period, all though this is perhaps open for future
debate.
Before whole heartily accepting the “new” we need to heed, respect the passage
of time and only then, after a respected reasonable interval, and a positive principled
“care research” result we can enthusiastically and confidently accept the “new” best
“approximate temporary truth.” For the record, in 1799, the “approximate temporary
truth” was bloodletting, blistering, and enemas.*
*On December 14, 1799, 3 prominent physicians-Craik, Brown, and Dick-gathered to
examine America’s first president, George Washington. He was complaining of severe throat
symptoms and was being treated with bloodletting, blistering, and enemas. Dick advised per-
forming an immediate tracheotomy to secure the airway. Both Craik and Brown were not keen
on trying tracheotomy and overruled that proposal. Washington was not involved in making
that decision. He most likely had acute epiglottitis that proved to be fatal at the end. If Dick
had prevailed, a tracheotomy could have saved Washington’s life. Human factors analysis of
these events shows that his physicians were totally fixated on repeating futile treatments and
could not comprehend the need for a radical alternative, like tracheotomy. That was aggra-
vated by an impaired situational awareness and significant resistance to change. Leadership
model was also based on hierarchy instead of competency, which might have also contributed
to Washington’s death. From: Abou-Foul AK. A Lesson on Human Factors in Airway Man-
agement Learnt From the Death of George Washington. Otolaryngol Head Neck Surg. 2020
Nov; 163(5):1000e1002. https://doi.org/10.1177/0194599820932127. Epub 2020 Jun 9.
PMID: 32513057.

8.4.2 Stem cellebased technology for ENS*

Other than preventing ENS by intelligent management of symptomatic inferior
turbinate enlargement (“hypertrophy”), a definitive curative treatment for ENS
does not exist; surgical or otherwise. These facts require the moral and ethical search
for data-driven studies that will guide rhinologists to provide successful care for our
ENS patients.
A potential possibility is stem cellebased technology that will become more
available and optimistically more useful at “some approaching” time in the future.
Using adipocyte-derived stem cells (ADSCs) has provided ENS patients with
renewed hope for the future. Xu et al. (2015) showed that these ADSCs produce
 8. Summary, future directions, and closing thoughts 227

cytokines that support tissue growth while diminishing mucosal injury and
increasing nasal mucociliary activity in their 28 ENS study patients.72 ADSCs
have been used as an implant material as have methylcellulose hydrogels, but these
materials are frequently resorbed after injection some months later requiring
reinjection.375
To date, different types of stem cells have been employed for managing aging,
wound healing, autoimmune diseases along with neurodegenerative, metabolic,
and musculoskeletal disorders. Adult stem cells, derivatives of embryonic and
induced pluripotent stem cells (iPS cells), have all been used clinically and are
currently involved in areas of active research.
For a variety of reasons, multipotent mesenchymal stem cells (MSCs) are the pri-
mary focus of cell-based therapies today and could conceivably be expanded for
ENS patients. Sources for these cell-based therapies include: bone marrow, adipose
tissue, umbilical cord, and placental tissue. Stem cells have a high proliferation po-
tential, in that they can differentiate into multiple cell types and replace damaged
cells, secrete growth factors maintaining local tissue regeneration, and are able to
migrate to damaged tissue sites after systemic injection. Additionally, they are
able to modulate the immune system, reducing inflammation of an affected area.
Neural crest-derived stem cells (NCSCs) have been suggested for therapeutic
ENS tissue engineering strategies, and research is currently underway in that area
too.382
In 2012, Shinya Yamanaka was awarded the Nobel Prize in Physiology or Med-
icine jointly with Sir John B. Gurdon for finding a way to “reprogram” adult cells to
become stem cells; iPS cells, capable of becoming any tissue in the body, except
placenta. For instance, iPS cells derived from skin or blood cells have been reprog-
rammed into an embryonic-like pluripotent state capable of empowering the growth
of boundless amounts of any type of human tissue cell desired or required for replac-
ing any tissue in the body. How about creating a new turbinate please? (Fig. 11.1).

8.5 Closing thoughts

We close with the humble phrase, “and the beat goes on,” a modest metaphor for the
rhythm of life itself, as a sustaining self-assured onward action into an unknown
future, no matter whatever passing medical fads, fashions, and whims come and
go, curiosity matters, integrity matters, knowledge matters based on solid scientific
study (RCTs) with impeccable statistical data.
This book is more than an exploration and conversation concerning the “empty
nose syndrome” with its diagnosis and treatment options. EBM is offered in a his-
torical and pragmatic context with its origins, applications, and limitations espe-
cially as it relates to the direction of future rhinologic investigation and current
clinical practice.
ENS is not to be ignored and discounted, especially as it can severely adversely
affect a person’s physical and emotional lives whose only first presenting complaint
may be difficulty breathing with a sense of suffocation. ENS might be suspected
228 CHAPTER 11 Review, finishing touches, and closure

FIGURE 11.1
In 2012, Shinya Yamanaka was awarded the Nobel Prize in Physiology or Medicine jointly
with Sir John B. Gurdon for finding a way to reprogram adult cells to become stem cells;
induced pluripotent stem cells (iPS cells). Pluripotent, embryonic stem cells originate as
inner mass cells within a blastocyst. These stem cells can become any tissue in the body,
excluding a placenta. Only the morula’s cells are totipotent, able to become all tissues
including a placenta Mike Jones-From English Wikipedia, Original description page/is
here. Comment: The source of pluripotent stem cells from developing embryos. Original
works by Mike Jones for Wikipedia. CC BY-SA 2.5 hide terms File Stem cells diagram.png
Created: May 3, 2006.
From English Wikipedia.

when the difficult breathing and the emotional impact seem disproportionate, exag-
gerated, compared to the clinical observations, yet these symptoms almost always
follow some type of previous turbinate surgery, the historical clue.

8.5.1 Inferior turbinate management

Turbinoplasty, a mucosal-sparing technique, combined with out-fracture
(lateralization)
In conclusion, for now, maximizing preservation of an intact turbinate mucosa is
our standard advice as it is the relatively steadiest surest way to prevent ENS.
Following the lead of Passali et al. for managing inferior turbinate enlargement
 8. Summary, future directions, and closing thoughts 229

(“hypertrophy”) which respects the results in 382 patients, after six years, of Passali
et al. with inferior turbinate submucosal resection (turbinoplasty) combined with
out-fracture (lateral displacement).211,216
In January of this year, 2023, several authors, from academic institutions, inim-
itably and uniquely drew attention to the amount of “airborne particle” aerosol pro-
duction (“surgery smoke plume”) generated by each of the many methods of inferior
turbinate reduction. Their stated goals were to determine the “ideal” method for
reducing an inferior turbinate by evaluating both outcomes and aerosol production
in the current age of:376
“.widespread communicable diseases, including but not limited to COVID-19,
HIV, and hepatitis, additional attention is necessary to balance outcomes with a
degree of generation of airborne particles when selecting a technique.” (Bold
italics added)
“Surgical management of the inferior turbinates includes radiofrequency abla-
tion (RFA), microdebrider-assisted turbinoplasty (MAIT), electrocautery, laser,
and ultrasound. Piezo-assisted turbinoplasty and a turbinate-specific coblation
wand are new additions to the literature.” (Bold italics added)
“MAIT and RFA are comparable, although MAIT demonstrated better long-term
outcomes in some studies and appears to generate fewer airborne particles.”
(Bold italics added)
“Studies evaluating the production of aerosols due to RFA are lacking. Ultra-
sound outcomes are also excellent and generate no aerosols, but the technique
has not been compared against the microdebrider.” (Bold italics added)
“Electrocautery can result in increased pain and crusting for patients and causes
the highest amount of aerosols.” (Bold italics added)
“Deficiencies of current studies, including a lack of comparison of aerosol gen-
eration, duration of follow-up, omission of outfracture, and inadequate random-
ized controlled trials among existing and new techniques, have limited the
identification of the best inferior turbinate reduction method.” (Bold italics
added)
“Given the durability of MAIT* and its minimal aerosol production, it can be
reinforced as the most sensible technique until further evidence is available.”376
(Bold italics and asterisk added) * microdebrider-assisted turbinoplasty (MAIT)
Unfortunately, for any patient, once turbinate tissue is resected beyond some
“critical” point, the exact amount of tissue that must be preserved to conserve
“optimal” function is currently unknown.
An injured or resected “organ of the nose,” the mucosa, with its supporting sub-
mucosa (lamina propria, stroma) may generate persistent pain (neurogenic post-
traumatic), persistent dryness, trigeminal thermoreceptor insufficiency, altered or
absent TRPM8 function, with a persistent sense of dyspnea and suffocation.
230 CHAPTER 11 Review, finishing touches, and closure

Consider that, submucosal healing scar tissue secondary to thermal trauma, or tissue
excision, may also lead to vascular submucosal damage, minimizing, better,
compromising the post-procedure epithelium of a robust blood supply. The adverse
obstructive effects of intervening scar tissue formation. Furthermore, how many of
these patients will require persistent psychological maintenance?

8.5.2 Surgical treatment of ENS

Surgical treatment for ENS is still problematic since many of the various surgical
interventions did not restore or return all mucosal functional integrity to normal
resulting in “long-term” patient benefit. Many of the surgical interventions, although
“promising,” have inadequate numbers and have not been conducted as “care
research” as an RCT and to date, 2022, have not been followed for a long enough
duration (most often in months less than a year) to add the term, “long term” in years
to the result.19,21,62,64e72,366e373

8.5.3 Medical management

As a consequence, the first action is to initiate medical management, recommended
and detailed above, for your ENS patients along with referral for competent profes-
sional psychological support if anxiety and depression are evident and supported by
the Generalized Anxiety Disorder questionnaire 7 (GAD-7) and the Patient Health
Questionnaire-9 (PHQ-9) for depression as you have likely already obtained the
Empty Nose Syndrome 6 question questionnaire (ENS6Q), Sino-Nasal Outcome
Test-20 for the assessment of possible Empty Nose Syndrome (SNOT-20). Suicidal
ideation may be lurking, perhaps prowling, just beneath a seemingly normal
personality.

8.5.4 Well-planned randomized controlled trials, “care research”

Well-planned RCTs, “care research,” are indispensable and imperative to answer the
questions surrounding surgical treatment alternatives for our ENS patients. Short-
term benefits may be reasonably tolerated if the initial surgical repair and “redo”
procedures are reasonably safe and significantly helpful in inducing, enjoining,
symptomatic relief. Doubtless, these decisions are for patient and surgeon to discuss
and resolve. In that spirit, hopefully, future positive results from successful “care
research” will provide a firm footed ethically directed successful scientific approach
with either a new “long-term” (measured in years) surgical solution or the “short-
term” application of repeated intermittent injections of a suitable submucosal
absorbable filler or effectively using stem cellebased technology for creating a func-
tioning “neoturbinate” to benefit our stressed and suffering ENS patients.

8.5.5 Finally
Eternally and evermore, be the questioning inquisitive skeptic, as science marches
on, two steps forward one step back, buttress your thinking on the vertebral column
of the next best “approximate temporary truth” from the next best RCT and apply
those trial truths to that one specific, unique, and particular patient in your compas-
sionate care.
 8. Summary, future directions, and closing thoughts 231

Grapple with ethical issues related to advances in medicine especially concern-

ing introducing “new” and “novel” surgical procedures. Our ethical responsibility,
when considering “new” innovative procedures or “reevaluations” of current pro-
cedures is to institute authorized “care research” trials to potentiate possible benefits
while curbing adverse effects by following all the criteria, for bias elimination (pla-
cebo control), after the CONSORT statement for reporting RCTs, to avoid publish-
ing flawed studies with conclusions that demand future reversal.213,266,299
Agha et al.269 stated that CONSORT requirements are necessary when reporting
RCTs in surgery:
“There is a clear need to ensure that medical research, especially relating to
clinical interventions, is carried out and reported to the highest possible stand-
ards.”266(Bold italics added)
The diagnosis of ENS is in the process of being codified, fully solidified, while
surgical treatment of ENS remains “a work in progress.” When dealing with turbi-
nate surgery, prefer the least invasive turbinate procedure possible to deal with a
nasal obstruction, ENS prevention.
Prasad’s work271 clarifies the fact that medicine aspires to apply the finest, most
accurate, information obtainable at the time, which allows for “knowledgeable
guesses,” which of course, is subject to change.
“We physicians and surgeons should tolerate ‘uncertainty’ acknowledging the
reality that medical theories and practices are subject to dislocation, disruption,
continuous change and improvements since that’s the nature of medical prog-
ress.”271 (Bold italics added)
Realize that there is a temporal quality to truth as described by Sir Karl R.
Popper, who introduced the concept of an “approximate temporary truth.”
Always buttress your thinking on the vertebral column of the best “approximate
temporary truth” from the best RCT, applying those truths to your patients.
Holmes (1900) writing in The New York Medical Journal recognized the nose as
a significant organ system and that minimal resection of the inferior turbinate was
superior to “extensive destruction.”80
In closing his September 1914 paper entitled, “A plea for the conservation of the
inferior turbinate,” published in the Atlanta Journal-record of Medicine, Dr. Albert
Mason beseeching readers wrote:
“In conclusion, I plead with you, both rhinologist and general practitioner, to
respect the function of the inferior turbinate and to save it when possible to do
so.”82 (Bold italics added)
After more than 100 years, this erudite opinion is still one with which many of us
adamantly agree and unwaveringly practice. Lastly, ever since Hippocrates, the
gravitational principled core of medicine has been and still is the dominating moral
authority of: the interest of the patient is the only interest of concern.
Appendix

This appendix contains seven items:

1. A brief history of Professor Maurice H. Cottle, MD
2. The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q)
3. The Sino-Nasal Outcome Test 20e25 (SNOT20-25) for ENS (questionnaire)
4. Nasal Obstruction Symptom Evaluation (NOSE) Instrument (questionnaire)
5. The cotton test, and how to perform it
6. The questionnaire for Generalized Anxiety Disorder (GAD-7)
7. The Patient Health Questionnaire-9 (PHQ-9) for depression

1. A brief history of Professor Maurice H. Cottle, MD

(1898e1981), and his “smalling” operations for nasal
atrophy from his 1958 paper374
Professor Maurice H. Cottle, MD, of Chicago used the idea of a “nasal cavity nar-
rowing,” a “nose reducing” or “smalling” operation for treating nasal atrophy, in the
mid-20th century.374 Today, these “narrowing operations” are regularly termed an
endonasal microplasty or an inferior meatus augmentation procedure (IMAP).
Dr. Cottle, born in London England, the eldest of seven children, was the founder
and first president of the American Rhinologic Society (1954) and cofounder of the
International Rhinologic Society with Professor HAE van Dishoeck (1963) of the
Netherlands. Cottle was an untiring educator, organizing and teaching nasal surgical
dissection courses worldwide (“The Cottle Courses”),a incorporating live surgical
demonstrations. He held the mantle as a major contributor to rhinologic thinking
in the mid-20th century, urging and practicing nasal functional testing, rhinomanom-
etry, commitment to conservative septo-rhinoplastic surgery, with the “push-down”
of the nasal dorsum in rhinoplasty, now called “dorsal preservation” and turbinate
conservation, whenever possible. Furthermore, as a physician and surgeon, the
consummate, and most eminent rhinologist of his time, he was also a medical author,
investigator as nasal physiologist, amateur musician as violinist playing in string
quartets, hosting at his home musical luminaries of the day including Sergei Rach-
maninov, Sergei Prokofiev, Vladimir Horowitz, Nathan Milstein, and singer Marian

a
One of us (EBK) first attended the Chicago “Cottle Course” in 1967 as a student and later as a
teacher for a number of years (18) until the founder’s death in Chicago in May 1981.
233
234 Appendix

Anderson among other personalities. He married the acclaimed Steinway artist Gitta
Gradova, a Chicago born pianist, who made her debut at the age of 19 in a recital at
Town Hall in New York City playing the “Dante” sonata of Liszt, Handel, Brahms,
Scriabin, and Chopin Waltz (Sostenuto) in E-flat major. Together they raised two
children, a son Tom, a practicing psychologist, and a daughter Judy, a noted cabaret
artist. He was major collector of both Chinese ceramics, Eskenazi Ltd. (book), and
Japanese woodblock prints, exhibited at several museums, among other artistic pur-
suits. Truly, a man for all seasons.

2. The Empty Nose Syndrome 6-Item Questionnaire strongly

suggests (confirms) ENS if the score is greater than >11
The Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) was validated using the
Sino-Nasal Outcome test (SNOT-22), but in addition, the ENS6Q presents 6 simple
questions (with a score of 1e5 points each) that can be a helpful in screening/con-
firming the diagnosis of ENS. A score 11 (but especially >15) out of a maximum
score of 30 strongly suggests the presence of ENS in the appropriate clinical
scenario.31

No
problem/
not Very Extremely
Symptom applicable mild Mild Moderate Severe severe
Dryness 0 1 2 3 4 5
Sense of 0 1 2 3 4 5
diminished nasal
airflow (cannot feel
air flowing through
your nose)
Suffocation 0 1 2 3 4 5
Nose feels too open 0 1 2 3 4 5
Nasal crusting 0 1 2 3 4 5
Nasal burning 0 1 2 3 4 5
ENS6Q, Empty Nose Syndrome 6-Item Questionnaire.

3. Sino-Nasal Outcome Test 20e25 (SNOT20-25) for ENS

This outcome test is from (Table 1):
Huang CC, Wu PW, Lee CC, Huang CC, Fu CH, Chang PH, Lee TJ. Comparison
of SNOT-25 and ENS6Q in evaluating patients with empty nose syndrome.
 Appendix 235

Table 1 The Sino-Nasal Outcome Test-25 for the assessment of empty nose
syndrome.343,348

1 Need to blow nose

2 Sneezing
3 Runny nose
4 Cough
5 Postnasal discharge
6 Thick nasal discharge
7 Ear fullness
8 Dizziness
9 Ear pain
10 Facial pain/pressure
11 Difficulty falling asleep
12 Waking up at night
13 Lack of good night’s sleep
14 Waking up tired
15 Fatigue
16 Reduced productivity
17 Reduced concentration
18 Frustration/restlessness/irritability
19 Sadness
20 Embarrassment
ENS-specific symptoms
21 Dryness
22 Difficulty with nasal breathing
23 Suffocation
24 Nose is too open
25 Nasal crusting
Each question is evaluated on a Likert scale of 0e5, with 5 being most severe.ENS, empty nose
syndrome.

Laryngoscope Investig Otolaryngol. February 28, 2022;7(2):342e348. https://doi.

org/10.1002/lio2.767. PMID: 35434317; PMCID: PMC9008176.

4. Nasal Obstruction Symptom Evaluation Instrument

Details are found in the original source
Stewart MG, Witsell DL, Smith TL, Weaver EM, Yueh B, Hannley MT. Develop-
ment and validation of the Nasal Obstruction Symptom Evaluation (NOSE) scale.
Otolaryngol Head Neck Surg. 2004;130:157e163.
236 Appendix

“Conclusions and relevance: The NOSE scale is an important tool for gauging
symptoms in patients with nasal obstruction.” From Lipan, MJ, Most, SP. Develop-
ment of a severity classification system for subjective nasal obstruction. Facial Plast
Surg. 2013;15(5). 358e361. https://doi.org/10.1001/jamafacial.2013.344.
The Nasal Obstruction Symptom Evaluation (NOSE) Instrument is a patient
questionnaire that asks five questions.
1. Nasal congestion or stuffiness
2. Nasal blockage or obstruction
3. Trouble breathing through my nose
4. Trouble sleeping
5. Unable to get enough air through my nose is during exercise or insertion
The patient is asked to grade the condition as it affected them over the past
month.
The responses may range from not a problem, scored zero (0), very mild prob-
lem, scored 1, moderate problem, scored 2, fairly bad problem, scored 3, severe
problem, scored 4.
The nose score scale is calculated by the sum of the score multiplied by 5 with a
possible score of 100 for an estimate of nasal obstruction as follows: Mild (range
5e25), Moderate (range 30e50), Severe (range 55e75), Extreme (range 80e100).

5. The cotton test, and how to perform it

Thamboo et al.32 used the ENS6Q to validate an office-based physical examination
maneuver, referred to as the cotton test, as another provocative adjunct valuable in
confirming the diagnosis of ENS. For the cotton test, patients are to complete
ENS6Q testing in three conditions:
1. Precotton placement, ENS6Q testing
2. With cotton in place (in situ) after 20e30 min, ENS6Q testing
3. Postcotton (after cotton removal), ENS6Q testing
The cotton test:
First complete the ENS6Q test prior to starting the cotton test. In an unmedicated
nose, i.e., in the absence of any topical intranasal sprays, place a dry cotton (plug),
usually in the region of previously resected head(s) of the inferior turbinate(s) in
the patent inferior meatal space, unilaterally or bilaterally, that was partially
or completely devoid of inferior turbinate tissue. The cotton remains in place
for 20e30 min and with the cotton in place repeat ENS6Q testing. The cotton
test is “positive” if the patient reports a reduction of their nasal symptom severity
score on ENS6Q testing with the cotton in place compared to pretest the ENS6Q
score.32
 Appendix 237

Subsequently, if patients have improvement in symptoms with the cotton test,

they might benefit from potential inferior turbinate augmentation procedures
(IMAPs).

6. Generalized Anxiety Disorder (GAD-7) test

Details are found in the original source
“Results: A 7-item anxiety scale (GAD-7) had good reliability, as well as crite-
rion, construct, factorial, and procedural validity.” From the original source: Spit-
zer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing
generalized anxiety disorder: the GAD-7. Arch Intern Med. May 22, 2006;
166(10):1092e1097.
The result provided by the GAD-7 is aimed at revealing whether an anxiety dis-
order is present and to what degree.
The original study involved a cohort of 2740 adult patients belonging to 15 pri-
mary care clinics in the United States. Following the application of the questionnaire
(within a week), 965 of these patients have been referred for an interview (tele-
phone) with a mental health professional.
Recommended usage
The GAD-7 should be used in association with other anxiety scales, such as the
Hamilton scale, especially when there are concerns about the mental health status of
the patient. The application of the questionnaire should be followed by other ques-
tions, related to other experiences and symptoms of the patient.

7. Patient Health Questionnaire-9 test for depression

Details are found in the original source
“Conclusion: In addition to making criteria-based diagnoses of depressive dis-
orders, the PHQ-9 is also a reliable and valid measure of depression severity. These
characteristics plus its brevity make the PHQ-9 a useful clinical and research tool.”
From the original source: Kroenke K, Spitzer RL, Williams JB. The PHQ-9:
validity of a brief depression severity measure. J Gen Intern Med. 2001;16:
606e613.
“The PHQ-9 is the 9-item depression module from the full PHQ. Major depres-
sion is diagnosed if five or more of the nine depressive symptom criteria have been
present at least “more than half the days” in the past 2 weeks, and 1 of the symptoms
is depressed mood or anhedonia.”
“One of the nine symptom criteria (“thoughts that you would be better off dead
or of hurting yourself in some way”) counts if present at all, regardless of duration.
238 Appendix

As with the original PRIME-MD, before making a final diagnosis, the clinician is
expected to rule out physical causes of depression, normal bereavement, and history
of a manic episode.”
“For most analyses, the interpretation of the PHQ-9 score was divided into the
following categories of increasing severity: 0e4, 5e9, 10e14, 15e19, and 20 or
greater.”
“As a severity measure, the PHQ-9 score can range from 0 to 27, since each of the
9 items can be scored from 0 (not at all) to 3 (nearly every day). An item was also
added to the end of the diagnostic portion of the PHQ-9 asking patients who checked
off any problems on the questionnaire: “How difficult have these problems made it
for you to do your work, take care of things at home, or get along with other people?”
Above quotations from the original source: Kroenke K, Spitzer RL, Wil-
liams JB. The PHQ-9: validity of a brief depression severity measure. J Gen
Intern Med. 2001;16:606e613.
Index
‘Note: Page numbers followed by “f” indicate figures and “t” indicate tables.’

A C
Adenoidectomy, 169 The Canadian Medical Association Journal,
Adenotonsillectomy, 169 97e98
Adipocyte-derived stem cells (ADSCs), 66, Canadian Task Force on the Periodic Health Ex-
226e227 amination, 98, 98t
Aggravated anxiety, 67 Carbon dioxide exchange, 25
Aggressive surgery, 3 Celebrex, 179
Aging, 53 Centers for Disease Control and Prevention, 180
Airflow analysis, 195 CFD. See Computational fluid dynamics (CFD)
Allografts, 66 Chronic rhinosinusitis (CRS), 112, 195
Alveolar ventilation, 25 Churg-Strauss syndrome, 50e51
American Academy of Pediatrics, 180 Clinical judgment, 144
American Journal of Rhinology, 173 Clinical practice guidelines (CPGs), 4, 158e165,
American Medical Association (AMA), 183
147 abstract, 161e165
American Rhinologic Society, 1, 20, 185 defined, 160
Antimicrobial proteins, 25e28, 186 key points, 161
Approximate temporary truth, 2, 7, 116, nonobedience, 160
167 Clinical reasoning, 104
Atrophic rhinitis, 40e54, 71, 181 Clinical surgical care, 147
primary, 47e49 Clustered regularly interspaced short palindromic
secondary, 49 repeats (CRISPR), 7
Autism, 180 Coblation-assisted turbinoplasty (CAT), 125e126
Autoimmune diseases, 50e51 Cochrane Methodology Register, 176e177
Autologous dermal fat (ADF), 211 Cognitive function, 195
Autologous stromal vascular fraction (SVF), Cold-knife techniques, 200
65 Computational fluid dynamics (CFD), 25, 190,
Autonomic nervous system, 28 192
Computational models, 59
B Computerized tomography (CT), 8, 8f, 10f,
Beck Anxiety Inventory (BAI), 187, 190 188e189, 192
Beck Depression Inventory, updated version, cavernous expansion, of intranasal airway, 33, 34f
(BDI-II), 187 inferior turbinates, 33, 34fe35f, 40fe41f
Belmont report, 138e139 reduction of, 38f
Beta-tricalcium phosphate, 66 maxillary sinus, 33, 39f
Bextra, 179 middle turbinates, 33, 35fe38f, 40fe41f,
Bias, 4, 177 107e108, 108fe109f
Bilateral concha bullosa, 113, after septectomy and subtotal resection, 110f
113f atrophic change of, 38f
Biopsy, 80t, 95e96 bilateral concha bullosa, 113, 113f, 116f
B lymphocytes, 28 frontal sinusitis, 111f
Breathing (respiration), 185 nasal septal deformity, 33, 37f
tests, 189 rhinoplasty, 33, 42fe44f
Breathlessness, 33 turbinate tissue, 58
British Medical Association, 69e70 Concha bullosa, 87
British Medical Journal, 97, 155 Conflict of interest (COI), 4, 162, 183
Bronchospasm, 59 Confounding variable, 158

263
264 Index

Conservative turbinoplasty, 6 incidence of, 1

Consolidated Standards of Reporting Trials management, 221
(CONSORT) statement, 4, 6, 155e157, medical treatments, 63e65, 200e204, 221, 230
183, 212e213, 223 D-panthenol, 203e204
Copernicus, 179 emotional support, 203
Cotton test, 55, 189, 236e237 hypertonic saline, 201e202
CPGs. See Clinical practice guidelines (CPGs) nasal irrigations, 64
Crime and Punishment, 7 nasal mucosal moistening agents, 64, 64t
Cryosurgery, 86 pain management, 201
Cryotherapy, 123 premarin nasal sprays, 204
Cyclooxygenase-2 (COX-2), 179 rhinitis medicamentosa, 202e203
Cytokines, 28, 66, 186 saline irrigations, 64
Wilson’s solution, 202
D mental health, 220e221
David Kennedy, MD, 173 mucopurulent postnasal discharge, 39, 47f
David Sackett, M.D (“father” of evidence-based nasal endoscopy, 189
medicine, EBM), 3, 97e106, 212 pathophysiology of, 57e58, 194e199, 221
Declaration of Helsinki, 138, 147e148 airflow analysis, 195
Defensins, 25e28, 185 anatomic features, 195
Depression, 237e238 cognitive function, 195
Desiderio Passali, MD, 6, 121e122, 128e129, computational models, 59
131, 135, 137, 140, 183, 199e200, 203, computerized tomography (CT), 58
211, 216e219, 225e226, 228e229 demographics, 195
Diffusor function, 76, 185 diagnostic testing, 195
Disease tolerance, 61 mental health, 195
Dorsal preservation, 233e234 mucociliary apparatus, 61
D-panthenol, 203e204 mucosal physiology/innate immunity,
Duncavage technique, 112 196
Dyspnea (breathlessness), 181 nerve growth factor (NGF), 198
olfactory function, 195
E phantom limb pain, 58
physiologic and pathologic conditions,
EBM. See Evidence-based medicine (EBM)
59
Editors, 175
suffocation, 59
Efficacy trials, 208
symptomatology, 195
Egbert Huizing, MD, 7, 29, 49, 75e77, 118, 128,
wide open airway, 196e197
130, 138, 215, 218
pertinent nasal physiology, 185e186
Electrocautery, 86, 122, 127
phantom limb pain, 58
Empiricism, 140e142, 224e225
physical examination, 220
Empty nose syndrome (ENS), 8f, 40e54, 181,
physiopathology of, 192
227e231
preliminary treatment, 182
computerized tomography (CT), 8, 8f
prevention, 3, 67e68, 199e200
definition of, 33, 219
inferior turbinate(s), 200
diagnosis/diagnostics of, 39, 54e56,
middle turbinate(s), 200
220
PubMed database, 9, 11te19t
emotional torment, 181
regarding children, 218e219
etiology of, 193e194
replacement, of medical practice, 213e214
exists, 185
reversal, of medical practice, 213e214
features of, 1
Sino-Nasal Outcome Test 20-25 (SNOT20-25)
free online encyclopedia, 9, 9f
for, 234e235, 235t
iatrogenic condition, 33
stem cell-based technology, 226e227
imaging, 189, 220
 Index 265

surgical treatment, 65e67, 204e211, 222, 230 randomized controlled trials (RCTs), 98
surgical trials for, 222e226 rationalism, 141
symptoms of, 39, 45t, 55, 186e188, 219e220 scientific evidence, 97
diagnostic investigations for, 187 External validity, 152
history and, 188
indicators, 186 F
suicidal ideation (thoughts), 187 Facebook, 9
testing in, 189e193 Ferris Smith forceps, 113, 115f
breathing tests, 189 Food and Drug Administration (FDA), 153
computational fluid dynamics (CFD), 190 Functional magnetic resonance imaging (fMRI),
cotton test, 189 195
menthol test, 189 Functional residual capacity of the nose (FRCn),
nasal nitric oxide test levels, 189 85e86, 193
olfactory test, 189
psychological testing, 190
tissue biopsy, 190e193
G
Generalized Anxiety Disorder (GAD 7), 187, 190,
validated diagnostic instruments, 220
204
Empty Nose Syndrome 6 Questionnaire (ENS6Q)
Genetic engineering, 7
questionnaire, 55, 188, 191, 200
Gentamycin, 201
ENS. See Empty nose syndrome (ENS)
Geriatric rhinitis, 53
ENS web sites (multiple languages), 1, 20
Granulomatosis with polyangiitis (formerly
Environmental irritants, 93
Wegener’s granulomatosis), 50e51, 52t
Eosinophilic granulomatosis with polyangiitis
Granulomatous disorders, 49e50
(formerly Churg- Strauss syndrome),
Guideline development groups (GDGs), 160e161
50e51, 52t

H
Epithelial mucosal destruction, 118
cryotherapy, 123
Hamilton Anxiety Scale, 190
electrocautery, 122
Hamilton Depression Scale, 190
lasers, 122
Heinz Stammberger, MD, 107
treatment groups, 121
High sensitivity C-reactive protein (hsCRP),
Epithelial mucosal preservation, 118, 123e127
11te19t
coblation, 125e126
Human beta-defensin 1 (hBD-1), 186
conchal bone reduction only, 124
Hyaluronic acid (HA), 65
electrocautery, 127
Hydroxyapatite, 66
microdebrider, 124e125
Hyperplasia (increase in cell number), 94e95
radiofrequency turbinoplasty, 125
Hypertonic saline irrigations (home recipes), 64,
soft tissue and conchal bone reduction, 124
201e202, 221
submucosal soft tissue reduction only, 123e124
Hypertrophy (increase in cell size), 3, 49, 69e70,
ultrasound, 126e127
94e95, 117, 138e139
Ethmoid sinus, 33, 37f
Evidence-based medicine (EBM), 97, 117e118,
135e136, 182e183, 212 I
clinical reasoning, 104 Iatrogenic wonderland, 56
Cochrane Collaboration, 103 Idiopathic midline granuloma, 49e50
criticism, 104 Immunoglobulins (IgA), 186
defined, 97 Immunoglobulins (IgG), 186
empiricism, 141 Induced pluripotent stem cells (iPS cells), 227,
expert opinion, 97 228f
grading system, 100, 101t Inferior meatus augmentation procedure (IMAP),
levels of evidence (LOEs), 98, 98te99t 206
for prognostic studies, 99t Inferior turbinates, 33, 34fe35f, 40fe41f, 200
for therapeutic studies, 100t anatomy of, 88e92
anterior mask rhinomanometry, 93fe94f
266 Index

Inferior turbinates (Continued) submucosa, 119

in females, 88 surgical and nonsurgical procedures, 117e134,
intranasal mucosal biopsy, 88, 88f 119t
in males, 88 treatment, 118
nasal cycle, 89, 91fe92f turbinoplasty, 120
nasal mucus membrane, 89f Inflammatory response, 25e28
nasal respiratory cilia, 90f Institute of Medicine (IOM), 160
nasal venous sinuses, 91 Interleukins (Ils), 28
subepithelial layer, 89 Internally validity, 152
venous capacitance vessels, 90 Internal nasal valve, 21e29, 22f, 24f
enlargement, 117, 215e217 International Journal of Pediatric Otorhinolar-
clinical practice guidelines (CPGs), 158e165 yngology, 169
CONSORT requirements, 155e157 International Peer Review Congress, 5e6
empiricism vs. rationalism, 140e142 Intranasal atrophy, 39, 45f, 48f
evidence-based proposals, 215e217 diagnostic workup for, 51
obligations and accountability, 154 Intranasal biopsy, 60
placebo effects, 145e146 Intranasal crusting, 39, 46f
practice replacement, 165e168 Intranasal trigeminal functional testing, 192
propensity score matching (PSM), 157e158 Intraturbinal turbinoplasty, 76
randomized controlled trials (RCTs), 136e137
reversal, 165e168 J
“sham” surgery, 149e151 The Journal of General Internal Medicine, 159
surgical innovations, 154 Journal of Medical Ethics, 143e144
epithelial mucosal destruction, 118 Journals, 175. See also Medical journals
cryotherapy, 123
electrocautery, 122
lasers, 122
K
Klebsiella pneumoniae ozaenae, 25e28, 43,
treatment groups, 121
47e49, 181
epithelial mucosal preservation, 118, 123e127
Klebsiella pneumoniae rhinoscleromatis, 43
coblation, 125e126
conchal bone reduction only, 124
electrocautery, 127
L
Lactoferrin (Lf), 186
microdebrider, 124e125
The Lancet, 25, 69e70
radiofrequency turbinoplasty, 125
The Laryngoscope, 7
soft tissue and conchal bone reduction, 124
Laser surgery, 86
submucosal soft tissue reduction only,
Legal Aid Board, 180
123e124
Leprosy, 49e50
ultrasound, 126e127
Lethal midline granuloma, 49e50
epithelium, 119
Levels of evidence (LOEs), 98, 98te99t
external surgical resection, 120
clinical question, 102e103
histopathology, 131e134
for prognostic studies, 99t
management, 228e230
for therapeutic studies, 100t
out-fracture (lateralization) techniques, 127e131
The Logic of Scientific Discovery, 2,
reduction, 38f, 117e134, 119t, 169
167
adults, 169
Lung hyperventilation, 25
children, 169
Lymphoma, 49e50
conservative inferior turbinoplasty approach,
Lysozyme (Ly), 186
170e172
outcomes for, 172t
radiofrequency volumetric tissue reduction M
(RVTR), 170 Malodor control agents, 63
study characteristics, 171t Maurice Cottle, MD (“father” of modern
symptom grading tools, 170e172 rhinology), 85, 187, 222e223
 Index 267

Maxillary sinus, 33, 37f, 39f Mucosal physiology/innate immunity, 196

Mayo Clinic, 1, 8f, 10f, 21e24, 33, 34fe41f, Mycobacterial tuberculosis, 49e50
44fe46f, 48f, 53e54, 108fe111f, 110,
128, 201e202 N
Measles, mumps, and rubella (MMR) vaccine, 180 Nasal aerodynamics, 59
Medical journals, 5 Nasal airway obstruction, 39
editors, 175 Nasal airway resistance, 25
funding mechanisms, 175 Nasal anatomy, 185
peer review, 176e177 Nasal atrophy, differential diagnosis of, 49e54, 52t
piercing perspicacious questions, 176 Nasal breathing, 2e3, 24
problems in, 177 Nasal crime, 3, 7, 29, 218
responsibilities, 176 Nasal cripple, 1, 20
tools, 177 Nasal cycle, 89, 91fe92f, 93
Medical treatments, 63e65 Nasal dryness, 53, 53t
nasal irrigations, 64 symptoms of, 58
nasal mucosal moistening agents, 64, 64t Nasal endoscopy, 189
saline irrigations, 64 Nasal epithelium, 132
Medpor, 66 Nasal irrigations, 64
Mental health, 195, 220e221 Nasal mucosa, 2, 25e28, 60f, 132, 186
Menthol test, 189 Nasal mucosal moistening agents, 64, 64t
Mesenchymal stem cells (MSCs), 227 Nasal nitric oxide test levels, 189
Metaplasia, 94e95 Nasal obstruction, 66
Microdebrider-assisted turbinoplasty (MAT), Nasal Obstruction Symptom Evaluation (NOSE),
124e125 235e236
Middle turbinates, 33, 35fe38f, 40fe41f, 200 Nasal physiology, 21e29
anatomy of, 87e88 Nasal resistance, 25, 193
classification, 88 Nasal respiratory cilia, 90f
concha bullosa, 87 Nasal septal deformity, 33, 37f
osseous skeleton, 87 Nasopulmonary reflex, 59
atrophic change of, 38f National Institute of Health (NIH), 183e184
enlargement, 214 Nebulizer (spray) method, 64
management of, 107e116, 114f Neglect external validity, 152
airway obstruction, 113 Neil Med sinus rinse, 202
bone scissor cut, 114f Nerve growth factor (NGF), 58e59, 198
chronic rhinosinusitis (CRS), 112 Neural-crest derived stem cells (NCSCs), 227
collapse of, 115f Non-surgical turbinate reduction adjunctive pro-
computerized tomography (CT), 107e108, cedures (n-sTRAPs), 2, 33, 40e43,
108fe109f 53e54, 189, 194
Duncavage technique, 112
Ferris Smith forceps, 113, 115f
inflammatory process, 112
O
Olfaction, 21e29, 185
olfactory cribriform region, 107
function, 195
outcomes, 110
test, 189
preservation, 107
Open Payments Database (OPD), 164
retrospective analysis, 112
Osseous skeleton, 87
secondary frontal sinusitis, 110, 111f
Out-fracture (lateralization) techniques, 127e131
Minnesota Multiphasic Personality Inventory
combined with other procedures, 128e131
(MMPI), 53e54, 190, 201
solitary-isolated and sole intervention, 128
Moisturizing agents, 63
Oxford Centre for Evidence-Based Medicine, 103
Monika Stenkvist, MD, 33
Oxygen exchange, 25
Mucociliary apparatus, 61
Ozena, 47e49, 81. See also Primary atrophic
Mucopurulent postnasal discharge, 39, 47f
rhinitis
268 Index

P “care research” trial, 145

Pain management, 179 clinical judgment, 144
Paradoxical nasal obstruction, 25, 181, 219 CONSORT, 156
Paradoxical obstruction, 33 empiricism, 141
Partial turbinectomy, 86e87 evidence-based medicine (EBM), 98
Patient Health Questionnaire (PHQ-9), 187, 190, evidence first, 144e145
204 levels of evidence (LOEs), 100
depression, 237e238 limitations, 151e153
Pediatric surgery, 6 external validity, 152
Peer Review Congress, 5e6, 177 generalizability, 152
Peer reviewers, 5, 175e176 internally validity, 152
comprehension, 177 neglect external validity, 152
tools, 176e177 not needed, 139e140
Peptides, 25e28 peer review process, 177
Pertinent nasal physiology, 185e186 placebo control, 6
Phantom limb pain, 58 propensity score matching (PSM), 158
Physiologic disease entity, 55 randomization in surgical practice, 142
Placebo effects rationalism, 141
ethics of using relative criteria, 143
medicine, 147 reversal, 4e5
surgery, 147e148 surgical and invasive procedures, 153e154
in research and practice outcomes, Rationalism, 140e142, 224e225
145e146 RCTs. See Randomized controlled trials (RCTs)
Plagiarism, 6, 175e180 Realistic management, 63
Plastipore, 66 Replacement/reversal, of medical practice,
Polymorphic reticulosis, 49e50 213e214
Postnasal surgery dysfunction community, 1 Research surgical trials, 147
Primary atrophic rhinitis, 43, 47e49, “sham” surgery, 149e151
81 Resistor function, 76, 185
incidence, 47e49 Respiration, 25
symptoms, 47e49 Rhinitis medicamentosa, 93
Propensity score matching (PSM), 4, 157e158, Rhinoplasty, 233e234
183 Rhinoscleroma, 43
Pseudodoxia Epidemica, 104e105 Rhinotillexomania, 194
PSM. See Propensity score matching (PSM) Risk of Bias tool, 177
Psychological testing, 190
Psychosocial distress, 61 S
Ptolemy’s work, 179 Saline irrigations, 64
PubMed database, 1, 11te19t, 185, Sarcoidosis, 49e50
205 Secondary atrophic rhinitis, 2, 40e43, 49, 71,
Pulmonary function, 193 80e81
aging, 53
R nonsurgical turbinate reduction procedures, 50t
Radical inferior turbinectomy, 219 surgical turbinate reduction procedures, 50t
Radical turbinate resection, 193e194 treatment modalities, 49, 51t
Radiofrequency turbinoplasty, 125 Secondary frontal sinusitis, 110, 111f
Radiofrequency volumetric tissue reduction Secretory IgA, 121e122, 139, 216
(RVTR), 170 Secretory phospholipase A2, 25e28
Randomized controlled trials (RCTs), 2, 4, Self-rated questionnaires, 190
136e137, 182e184, 213, 230 Senile rhinitis, 53
absolute criteria, 143 “Sham” surgery, 149e151
bias elimination, 6 clinical research, 150
 Index 269

medical care, 150 reduction, 117e134

proved, 149 injections, 86
Silent sinus syndrome, 130e131 middle turbinate, 107e116, 114f
Sino-Nasal Outcome Test-22 (SNOT-22), 195, airway obstruction, 113
198 bone scissor cut, 114f
Sino-Nasal Outcome Test 20-25 (SNOT20-25), chronic rhinosinusitis (CRS), 112
234e235 collapse of, 115f
Sir Karl Raimund Popper, 2, 7, 167, 184, computerized tomography (CT), 107e108,
231 108fe109f
Sjogren’s syndrome, 50e51 Duncavage technique, 112
Somatic symptom disorder (SSD), 201 Ferris Smith forceps, 113, 115f
Squamous metaplasia, 47e49, 94e95 inflammatory process, 112
mucociliary apparatus, 61 olfactory cribriform region, 107
Statherin, 25e28 outcomes, 110
Stem cell-based technology, 226e227 preservation, 107
Steven Houser, MD, 43, 66, 121e122, 193, retrospective analysis, 112
196e197, 207, 214, 219 secondary frontal sinusitis, 110, 111f
Submucosal (lamina propria, stroma) tissue, out-fracture (lateralization), 86
25e28, 33, 47e49, 54e55, 87, 88fe89f, physical examination, 93e95
90, 118e120, 133, 181, 186, 199, 217, resistor function, 76
229e230 Turbinate swelling, 93
Submucosal turbinoplasty, 189 Turbinate trauma, 20e21
Suffocation, 59 Turbinectomy, 136, 193
Suicide, 1, 187 defined, 121
Surgical clinical care, 183e184 Turbinoplasty, 86e87, 120
Surgical research trials, 183e184 coblation-assisted turbinoplasty (CAT), 125e126
Surgical treatments, 65e67 microdebrider-assisted turbinoplasty (MAT),
Syphilis, 49e50 124e125
radiofrequency, 125
T Turbulent air flow, 25
Therapeutic turbinate trauma (TTT), 181e182,
194, 204e206 U
The Three Musketeers, 178 Ultrasound, 126e127
Tissue biopsy, 190e193 turbinoplasty, 120, 216e217
T lymphocytes, 28 Upper lateral cartilage (ULC), 24f
Tonsillectomy, 169
Total inferior turbinectomy, 3, 7, 39, 46f, 69e70, V
80, 86e87 Vagus nerve, 59
Transient receptor potentials melastatin 8 Vioxx, 179
(TRPM8), 186, 191, 196e197, 207 Visual analog scale (VAS), 86, 122e123, 127, 129,
Treponema pallidum, 49e50 139
Turbinates
anatomy, 87e92
W
inferior turbinate, 88e92
Walter Messerklinger, MD, 107
middle turbinate, 87e88
Wikipedia, 9, 9f, 176
biopsy, 80t, 95e96
William M. Jarvis, MD, 69
diagnostic assessment tests, 80t, 95e96

Y
diffusor function, 76
enlargement, 70
YouTube, 9
inferior turbinate, 117e134
classification, 117
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