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Obesity and Lung Disease A Guide to Pathophysiology
Evaluation and Management 2nd Edition Anne E. Dixon
Digital Instant Download
Author(s): Anne E. Dixon, Erick Forno
ISBN(s): 9783031526954, 3031526953
Edition: 2nd
File Details: PDF, 13.76 MB
Year: 2024
Language: english
Respiratory Medicine
Series Editors: Sharon I. S. Rounds · Anne E. Dixon · Lynn M. Schnapp

Anne E. Dixon
Erick Forno Editors

Obesity
and Lung
Disease
A Guide to Pathophysiology, Evaluation,
and Management
Second Edition
Respiratory Medicine

Series Editors
Sharon I. S. Rounds, Brown University, Providence, RI, USA
Anne E. Dixon, University of Vermont, Larner College of Medicine
Burlington, VT, USA
Lynn M. Schnapp, University of Wisconsin - Madison, Madison, WI, USA
Respiratory Medicine offers clinical and research-oriented resources for
pulmonologists and other practitioners and researchers interested in respiratory
care. Spanning a broad range of clinical and research issues in respiratory medicine,
the series covers such topics as COPD, asthma and allergy, pulmonary problems in
pregnancy, molecular basis of lung disease, sleep disordered breathing, and others.
The series editors are Sharon Rounds, MD, Professor of Medicine and of
Pathology and Laboratory Medicine at the Alpert Medical School at Brown
University, Anne Dixon, MD, Professor of Medicine and Director of the Division of
Pulmonary and Critical Care at Robert Larner, MD College of Medicine at the
University of Vermont, and Lynn M. Schnapp, MD, George R. And Elaine Love
Professor and Chair of Medicine at the University of Wisconsin-Madison School of
Medicine and Public Health.
Anne E. Dixon • Erick Forno
Editors

Obesity and Lung Disease

A Guide to Pathophysiology, Evaluation,
and Management

Second Edition
Editors
Anne E. Dixon Erick Forno
Department of Medicine Pulmonary, Allergy, and Sleep Medicine
University of Vermont Larner Department of Pediatrics
College of Medicine Indiana University School of Medicine
Burlington, VT, USA Indianapolis, IN, USA

ISSN 2197-7372     ISSN 2197-7380 (electronic)

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Contents

1 
Effects of Obesity on Lung Function��������������������������������������������������������   1
Gregory G. King
2 Obesity-Mediated Alterations in Immune Function,
Host Defense, and Lung Disease �������������������������������������������������������������� 21
Anna Reichenbach, Silvia Cabrera Guerrero, and Deepa Rastogi
3 
Obesity, the Microbiome, and Lung Disease ������������������������������������������ 43
Jennifer L. Ingram and Yvonne J. Huang
4 
Genetics and Genomics of Obesity and Lung Diseases�������������������������� 73
Erick Forno
5 
The Western Dietary Pattern and Respiratory Health�������������������������� 83
Bronwyn S. Berthon, Lily M. Williams, Hayley A. Scott,
Evan J. Williams, and Lisa G. Wood
6 
Pathogenesis of Obstructive Sleep Apnea in Obesity������������������������������ 125
Susheel P. Patil and Jason Paul Kirkness
7 Obesity Hypoventilation Syndrome �������������������������������������������������������� 151
Alejandra C. Lastra, Nancy Stewart, and Babak Mokhlesi
8 
Obesity and Asthma: Epidemiology and Clinical Presentation������������ 181
Jessica Reyes-Angel and Erick Forno
9 
Obesity and Asthma: Metabolic Dysregulation�������������������������������������� 201
Fernando Holguin
10 
Obesity and Asthma: Endotypes and Mechanisms�������������������������������� 211
Arjun Mohan, Muhammad Adrish, and Njira L. Lugogo
11 
Asthma Management in Obesity�������������������������������������������������������������� 229
Anne E. Dixon and Sharmilee M. Nyenhuis
12 Obesity and Chronic Obstructive Pulmonary
Disease (COPD)������������������������������������������������������������������������������������������ 249
Frits M. E. Franssen

v
vi Contents

13 
Obesity, Metabolic Syndrome, and Pulmonary Hypertension�������������� 267
Jessica B. Badlam
14 
Association of Obesity and Thromboembolic Disease���������������������������� 289
Margarita Kushnir and Henny Billett
15 
Obesity and Respiratory Infections Including COVID-19�������������������� 301
Peter Mancuso
16 
Obesity and Lung Health in Children������������������������������������������������������ 321
Jason E. Lang and Dharini Bhammar
17 
Obesity and Acute Respiratory Distress Syndrome�������������������������������� 347
William G. Tharp and Renee D. Stapleton
18 Obesity and Mechanical Ventilation�������������������������������������������������������� 365
Lorenzo Berra and Luigi G. Grassi
19 
Obesity and COVID-19 in the Intensive Care Unit�������������������������������� 387
MaryEllen Antkowiak

Index������������������������������������������������������������������������������������������������������������������ 403
Contributors

Muhammad Adrish Section of Pulmonary, Critical Care and Sleep Medicine,

Baylor College of Medicine, Houston, TX, USA
MaryEllen Antkowiak Department of Medicine, Larner College of Medicine,
University of Vermont, Burlington, VT, USA
Jessica B. Badlam Division of Pulmonary Disease and Critical Care Medicine,
University of Vermont Medical Center, Burlington, VT, USA
Lorenzo Berra Massachusetts General Hospital, Boston, MA, USA
Harvard Medical School, Boston, MA, USA
Bronwyn S. Berthon Immune Health Research Program, Hunter Medical Research
Institute, The University of Newcastle, Newcastle, NSW, Australia
Dharini Bhammar Department of Internal Medicine, The Ohio State University,
Columbus, OH, USA
Henny Billett Division of Hematology, Department of Oncology, Montefiore
Medical Center and the Albert Einstein College of Medicine, Bronx, NY, USA
Anne E. Dixon Department of Medicine, Larner College of Medicine, University
of Vermont, Burlington, VT, USA
Erick Forno Department of Pediatrics, Indiana University School of Medicine,
Indianapolis, IN, USA
Pulmonary, Allergy, and Sleep Medicine, Riley Children’s Hospital,
Indianapolis, IN, USA
Frits M. E. Franssen Department of Research and Education, CIRO, Horn, The
Netherlands
Department of Respiratory Medicine, Maastricht University Medical Center,
Maastricht, The Netherlands
Luigi G. Grassi Ca Granda Maggiore Hospital, Milan, Italy

vii
viii Contributors

Silvia Cabrera Guerrero Children’s National Hospital, Washington, DC, USA

George Washington University School of Medicine and Health Sciences,
Washington, DC, USA
Fernando Holguin Division of Pulmonary and Critical Care Medicine, Department
of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
Yvonne J. Huang Division of Pulmonary/Critical Care Medicine, Department of
Internal Medicine, University of Michigan, Ann Arbor, MI, USA
Department of Microbiology and Immunology, University of Michigan, Ann
Arbor, MI, USA
Jennifer L. Ingram Division of Pulmonary, Allergy and Critical Care Medicine,
Department of Medicine, Duke University, Durham, NC, USA
Department of Pathology, Duke University, Durham, NC, USA
Department of Surgery, Duke University, Durham, NC, USA
Gregory G. King Department of Respiratory and Sleep Medicine, Royal North,
Shore Hospital, St Leonards, NSW, Australia
The Woolcock Institute of Medical Research and Northern Clinical School,
University of Sydney, Sydney, NSW, Australia
Jason Paul Kirkness Division of Pulmonary, Critical Care and Sleep Medicine,
University of Miami Miller School of Medicine, Miami, FL, USA
Margarita Kushnir Division of Hematology, Banner MD Anderson Cancer
Center, Phoenix, AZ, USA
Jason E. Lang Division of Pulmonary & Sleep Medicine, Department of Pediatrics,
Duke Clinical Research Institute, Duke University School of Medicine,
Durham, NC, USA
Alejandra C. Lastra Section of Pulmonary and Critical Care, The University of
Chicago, Chicago, IL, USA
Njira L. Lugogo Division of Pulmonary and Critical Care Medicine, University of
Michigan, Ann Arbor, MI, USA
Peter Mancuso Department of Nutritional Sciences, Graduate Program in
Immunology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Arjun Mohan Division of Pulmonary and Critical Care Medicine, University of
Michigan, Ann Arbor, MI, USA
Babak Mokhlesi Division of Pulmonary, Critical Care and Sleep Medicine, Rush
Lung Center, Rush University Medical Center, Chicago, IL, USA
Sharmilee M. Nyenhuis Department of Pediatrics, University of Chicago,
Chicago, IL, USA
Contributors ix

Susheel P. Patil Division of Pulmonary, Critical Care, and Sleep Medicine,

University Hospitals, Cleveland, OH, USA
Deepa Rastogi Children’s National Hospital, Washington, DC, USA
George Washington University School of Medicine and Health Sciences,
Washington, DC, USA
Anna Reichenbach Children’s National Hospital, Washington, DC, USA
Jessica Reyes-Angel Division of Pediatric Pulmonary Medicine, UPMC Children’s
Hospital of Pittsburgh, Pittsburgh, PA, USA
Department of Pediatrics, University of Pittsburgh School of Medicine,
Pittsburgh, PA, USA
Hayley A. Scott Immune Health Research Program, Hunter Medical Research
Institute, The University of Newcastle, Newcastle, NSW, Australia
Renee D. Stapleton Division of Pulmonary and Critical Care Medicine, Department
of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA
Nancy Stewart Division of Pulmonary, Critical Care and Sleep Medicine, The
University of Kansas, Lawrence, KS, USA
William G. Tharp Department of Anesthesiology, University of Vermont Larner
College of Medicine, Burlington, VT, USA
Evan J. Williams Immune Health Research Program, Hunter Medical Research
Institute, The University of Newcastle, Newcastle, NSW, Australia
Lily M. Williams Immune Health Research Program, Hunter Medical Research
Institute, The University of Newcastle, Newcastle, NSW, Australia
Lisa G. Wood Immune Health Research Program, Hunter Medical Research
Institute, The University of Newcastle, Newcastle, NSW, Australia
Effects of Obesity on Lung Function
1
Gregory G. King

Contents
Introduction 2
 dipose Tissue and Respiratory Mechanics
A 3
Intra-abdominal and Intrathoracic Pressures 3
Respiratory System Compliance 4
Lung Volumes 6
Spirometry 8
Breathing Pattern 9
Peripheral Airway Function: Oscillometric Impedance and Nitrogen Washout 9
Expiratory Flow Limitation During Tidal Breathing 11
Intrinsic PEEP and Dynamic Hyperinflation 12
Breathless During Exercise 12
Ventilation Distribution 13
Gas Exchange 13
Effects of Obesity on Respiratory Function in Disease 13
Interpretation of Lung Function 14
References 15

G. G. King (*)
Department of Respiratory and Sleep Medicine, Royal North Shore Hospital,
St Leonards, NSW, Australia
The Woolcock Institute of Medical Research and Northern Clinical School, University of
Sydney, Sydney, NSW, Australia
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature 1

Switzerland AG 2024
A. E. Dixon, E. Forno (eds.), Obesity and Lung Disease, Respiratory Medicine,
https://doi.org/10.1007/978-3-031-52696-1_1
2 G. G. King

Introduction

The accumulation of adipose tissue, leading to the development of obesity, has a

profound effect on human physiology, including significant effects on respiratory
function due to the mechanical effects of excess adipose tissue on the balance of
forces that normally act on the lung. In addition, adipose tissue produces hormones
and other mediators, collectively termed adipokines, which are associated with low-­
grade systemic inflammation that can act indirectly on the respiratory system.
However, at present, it is unclear whether this causes any measurable impairment in
respiratory function. The changes in lung function associated with obesity can lead
to respiratory symptoms in otherwise healthy people, which are accentuated in
those with respiratory disease, as a result of interaction between disease pathophysi-
ology and the direct and indirect effects of obesity. The outcomes of this interaction
are complex and differ according to the disease and the outcome of interest. The
major effects of obesity on lung function are summarized in Fig. 1.1 and suggest
that, at least in adults and older adolescents, many of the changes in lung function
result from changes in respiratory system mechanics and reduction in operating
lung volume, whereas others may be due to other non-volume-related factors. In
this chapter, the effects of obesity on lung function and the relationships

Fig. 1.1 The effects of obesity on lung function, illustrating likely mechanisms. See text for more
detailed discussion
1 Effects of Obesity on Lung Function 3

summarized in Fig. 1.1 will be reviewed along with the effects of these impairments
on respiratory symptoms. Some of the changes in lung function seen with obesity in
the paediatric population will be covered in Chap. 16 later in this book.

Adipose Tissue and Respiratory Mechanics

In adults over age 20, obesity is defined as a body mass index (BMI) >30 kg/m2.
However, BMI is a non-specific measure of body mass that includes both fat and
lean mass, without any account of differences in fat distribution. Central obesity is
associated with increased adipose tissue in the anterior chest and abdominal walls
and visceral organs, whereas peripheral obesity reflects adiposity located peripher-
ally on limbs, or in subcutaneous tissue. The effect of obesity on respiratory func-
tion is likely to be determined by the distribution of fat mass. Therefore, the increase
in abdominal and chest wall fat in central obesity is more likely to push the chest
wall inwards and push the diaphragm in a cranial direction, thus reducing thoracic
volume at functional residual capacity (FRC) and expiratory reserve volume (ERV).
A reduction in FRC is the most recognized abnormality in lung function due to
obesity, but it varies greatly between individuals—there being only a moderate rela-
tionship with BMI [1]. The heterogeneity in lung volume response is likely due to
variations in total fat mass, distribution of that fat, effects of ageing on the mechani-
cal properties of the lung, airways and chest wall, and variations in chest and lung
compliances. In addition, visceral fat is more metabolically active than subcutane-
ous fat, and its increase or dysfunction may therefore make a greater contribution to
low-grade systemic inflammation in obesity. Adipose tissue is also found inside the
thoracic cavity, predominantly as pericardial fat, which, when combined with
obesity-­associated increase in the volume of the heart and major blood vessels, can
reduce the volume of the thoracic cavity [2].

Intra-abdominal and Intrathoracic Pressures

Obesity is associated with chronic increases in intra-abdominal pressure that may

affect the pleural space by altering pressure across the diaphragm. Intra-abdominal
pressure is increased in obese subjects compared to non-obese [3, 4] and is greater
in men than women [4], likely due to the greater prevalence of central obesity in
men. Indeed, intra-abdominal pressure correlates with markers of central obesity,
such as the sagittal abdominal diameter [3, 4]. In addition, in contrast to intra-­
abdominal pressure, studies in supine anaesthetized subjects [3, 4] have shown that
abdominal obesity, measured by waist circumferences and by sagittal abdominal
diameter, is not correlated with pleural pressures. Since the relationship between
abdominal pressure and pleural pressure is mediated by the diaphragm, the lack of
correlation between the two may be due to compensatory increase in passive tension
in the diaphragm in response to increased intra-abdominal pressure in the obese.
Alternatively, factors other than increased abdominal pressures, such as changes in
4 G. G. King

a b c

Fig. 1.2 Compliance curves for the chest wall (CCW), lung (CL) and respiratory system (Crs) in
normal-weight (a) and obese individuals (b, c). Functional residual capacity (FRC) as indicated by
the solid line, where Crs is zero, is reduced in the obese individual. Crs, which is represented by the
slope of the linear portion, of the solid line above FRC, is reduced

the mechanical properties of the chest wall, may also contribute to the altered lung
volumes in obesity. Imaging studies of abdominal and thoracic fat have shown that
both regions make a significant contribution to impairments of lung function in the
obese [5].
Pleural pressures are also increased (i.e. less negative) in obese compared to non-­
obese adults at FRC. This is likely due to a rightward shift of the pressure-volume
curve of the chest wall due to mass loading (i.e. compliance is unchanged; see
below and Fig. 1.2) such that the outward recoil pressure from the chest wall is
reduced at any given volume, which lowers FRC, thus raising pleural pressure by
being on the lower part of the lung’s pressure-volume curve. However, pleural pres-
sure at FRC may even exceed atmospheric pressure in the dependent parts of the
lungs [3, 4], which would occur with greater mass loading of the chest wall and with
reduced lung elastic recoil (which would occur with age). The functional conse-
quence is closure of small airways with potential effects on gas exchange and inspi-
ratory threshold loading (increased inspiratory effort required to overcome the
positive pressure for lung inflation to occur).

Respiratory System Compliance

One might expect that the stiffness (or its inverse being compliance) of the respira-
tory system, which comprises the lungs and chest wall, may be increased in obesity,
due to structural alterations associated with obesity. There are, however, only a few
studies that examine this, which are old and involve few subjects, with varying
methodologies. Measurements of chest wall compliance require an absence of
respiratory muscle activity since muscle activity stiffens the chest wall, which is
difficult to achieve in non-paralysed subjects. Furthermore, supine oesophageal
measurements in obesity pose problems of measurement noise and interpretation.
1 Effects of Obesity on Lung Function 5

This probably explains the conflicting findings from those few studies. Taken
together, data suggest that both chest wall and lung stiffness may be increased in
some obese subjects, with considerable heterogeneity between individuals which
has not been explored. What is important however, from a clinical standpoint, is not
whether chest wall or lung mechanics are altered, but that there is considerable
variation in mechanical alterations due to obesity, which will have variable effects
on symptoms and underlying disease.
There are two seminal studies looking at respiratory system compliances in
awake obese individuals; both are from the 1960s and performed in adults [6, 7].
With small numbers of n = 12 obese subjects in upright and supine positions [6] and
n = 15 obese subjects in supine posture [7], oesophageal pressures were measured
over a range of lung volumes, which were induced by either sucking or blowing air
into a ‘tank respiratory’ (or ‘iron lung’) [7] or a body plethysmograph [6] to achieve
passive inflation or deflation. This allowed subjects to remain in the ‘relaxed’ state
where respiratory muscles were not activated. In both studies, chest wall compli-
ance was decreased, particularly in those with obesity-hypoventilation syndrome
[6]. In a more recent study of 14 obese, seated males, using a different methodology,
chest wall compliance was not affected by obesity [8]. There are three studies of
obese subjects under anaesthesia and paralysis, which removed respiratory muscle
contribution to chest wall compliance [9–11]. Chest wall compliance was reduced
in two studies by the same group [10, 11], but was normal in the other [9].
The results of studies looking at lung compliance are also conflicting. Lung com-
pliance was normal in the two studies from the 1960s [6, 7], as well as in a subse-
quent study of nine subjects [12]. The studies of anaesthetized and paralysed
individuals, however, revealed reduced lung compliances [9–11]. Again, these con-
flicting results need to be interpretated in light of the methodological challenges.
Static lung compliance is measured as the slope of volume versus pressure, over an
arbitrary volume starting at end-expiratory lung volume where the relationship
should be linear. However, airway closure makes the curve ‘S’ shaped, becoming
flatter (lower compliance) at lower lung volumes (which is what typically happens
to FRC in obesity), and so compliance measurements are affected by the volumes
over which they are calculated [12]. Increased pulmonary blood volume [13] and
increased alveolar surface tension due to a reduction in FRC may also potentially
contribute. Differences in methodology between studies including differences in
posture, effects of anaesthesia and mechanical ventilation and patient selection
mean that no strong conclusions can be made about whether obesity has any effect
on lung compliance.
Aside from uncertainties of whether chest and lung compliances are reduced in
obesity, the effects of mass loading seem much clearer. This is purely the effect of
greater weight on the chest wall and abdomen, which compresses the respiratory
system (reducing FRC) and increases the work of breathing, independently of any
change in compliance. Mass loading experiments suggest that loading the chest wall
produces a rightward shift of the chest wall’s pressure-volume curve (see Fig. 1.2b)
without a change in shape (compliance) [14]. FRC is decreased, and the respiratory
system compliance curve, which is the summation of the chest wall and lung curves,
6 G. G. King

is also right-shifted and the slope (compliance) may or may not be affected. Mass
loading of the abdomen, however, does reduce the compliance of the chest wall
(Fig. 1.2c) [14], which would then alter total respiratory system compliance. Thus,
during inspiration, the pressure required for any given tidal inspiration is greater,
due to the summation of mass loading effects on the chest wall and abdomen. The
differential effects of obesity on the chest wall versus abdomen may also partly
explain the conflicting results in the literature.

Lung Volumes

Relaxation Volume: FRC

Obesity has a major effect on resting lung volume, causing a reduction in lung vol-
ume at relaxation, when the recoil pressures of the lung and chest wall are equal and
opposite (Fig. 1.2). The relaxation volume of the lung usually equates to the func-
tional residual capacity (FRC), which is very commonly reduced in obesity [1, 10].
FRC is exponentially related to BMI [1, 10], with reduction in FRC being detected
even in overweight individuals [1]. This is illustrated in Fig. 1.3, which shows the
relationship between BMI and FRC in a study of young adults, aged 28–30 years
[15]. The reduction in FRC is also manifested by an increase in inspiratory capacity
(IC). With increasing severity of obesity, the reduction in FRC may become so
marked that the FRC approaches residual volume (RV), leaving the individual with
a negligible expiratory reserve volume (ERV) [1]. In fact, in many studies, the
reduction in ERV is one of the earliest and most marked changes in lung function
that occurs with increasing weight [16].
The relationship between BMI and FRC, shown in Fig. 1.3, is steeper in men
than in women. This difference in slope is likely to result from differences in the
prevalence of central obesity between men and women. Central obesity, associated

Fig. 1.3 Relationship

between BMI and FRC in
young men (open squares,
solid line) and women
(solid triangles, dashed
line)
1 Effects of Obesity on Lung Function 7

with greater fat deposition on the trunk and abdomen, is likely to have a greater
effect on respiratory system compliance than peripheral fat distribution. Reductions
in lung volumes are associated with both abdominal fat, measured by waist circum-
ference [17], waist-to-hip ratio [18] or abdominal height [19], and thoracic or upper
body fat, measured by sub-scapular skinfold thickness [20] or biceps skinfold thick-
ness [16]. Sutherland et al. [5] used a wide range of body fat variables to determine
the effect of fat distribution on lung volumes in healthy adults. Lung volumes were
only loosely associated with BMI; however, both dual-energy X-ray absorptiometry
(DEXA) and non-DEXA-derived measures of upper body fat showed highly signifi-
cant negative correlations with FRC and ERV in both men and women. Both
abdominal obesity and thoracic fat mass were similarly correlated with lung vol-
umes. Improvements in lung volumes such as FVC, FRC and ERV, following mod-
erate weight loss, were related to the cumulative loss of fat from the chest and
subcutaneous abdominal and visceral fat, all of which may affect the mechanical
function of the respiratory system [21].

Total Lung Capacity

In contrast, the effects of obesity on the upper and lower limits of lung volumes,
total lung capacity (TLC) and RV are modest. Increasing body weight is associated
with only small decrease in TLC [1, 22, 23], and RV is usually well preserved but
may even be reduced in severe obesity [2, 22, 24–26]. As a result, the RV/TLC ratio
remains normal or slightly increased in obese individuals [1, 25].
The magnitude of the reduction in TLC with increasing weight is proportionally
smaller than the effect on FRC, at least until BMI exceeds 35 kg/m2 [1]. Lung
restriction of the magnitude associated with restrictive lung disease, defined as TLC
below the lower limit of normal, is not commonly associated with obesity in the
absence of other diseases. Prospective studies show that TLC increases with weight
loss in both mild [27] and morbidly obese [28] subjects.
The reduction in TLC in the obese is likely at least partly due to impaired down-
ward movement of the diaphragm, due to increased abdominal mass and/or compli-
ance, which limits the room for lung expansion on inflation. In addition, deposition
of fat in sub-pleural spaces [29] or elsewhere in the intrathoracic cavity might
directly reduce lung volume by reducing the volume of the chest cavity. An explor-
atory study to investigate the mechanism for reduced TLC in obesity used MRI to
measure intrathoracic volumes in obese and non-obese men and found increased
mediastinal volume in the obese due to an increase in the volume of intrathoracic
fat, the heart and major blood vessels [2]. At full inflation, the proportion of the
intrathoracic volume occupied by inflated lungs was only 78% of the total in the
obese compared with 88% in the controls, suggesting that the increased mediastinal
volume may prevent full lung expansion in the obese and may therefore explain the
slight loss of TLC with increasing BMI. However, the marked loss of TLC in obese
subjects with lung restriction (TLC <80% predicted) was not explained by increased
mediastinal volume, suggesting that other factors, such as reduced expansion of the
8 G. G. King

thoracic cage and reduced diaphragmatic excursion, may also be important in this
subgroup [2]. Since respiratory muscle strength and maximum inspiratory and expi-
ratory pressures have been shown to be intact in obesity [24, 30, 31], it is unlikely
that these would be an important determinant of obesity-related reduction in TLC.

Spirometry

Vital capacity (VC) is reduced due to a small reduction in TLC, but relative preserva-
tion of RV. There is a progressive linear decrease in VC with increasing BMI that
parallels the decrease in TLC [1]. Similarly, increasing BMI is also associated with a
decrease in both FEV1 and FVC [26, 32, 33]. However, this effect is small, and both
FEV1 and FVC are usually within the normal range in healthy obese adults [32, 33]
and children [34]. As a result, the FEV1/FVC ratio, which is a marker of airway
obstruction, is usually well preserved or increased [20, 26, 33–35], even in morbid
obesity [25]. Figure 1.4 shows data from a population of 1971 adults aged between
17 and 73 years [32] based on the per cent of predicted values. Although FVC is
affected to a greater extent than FEV1 as BMI increases, FEV1/FVC ratio remains
normal across the weight groups, even in the severely obese group. Studies looking
at the effect of body fat distribution on spirometry have shown that abdominal obe-
sity is a stronger predictor than either weight or BMI of reductions in FEV1 and FVC
[19, 36], with one very large study of over 130,000 people suggesting that abdominal
obesity may also be a risk for reduced FEV1/FVC ratio [36]. Moreover, weight gain
following smoking cessation [37] or with increasing age [38] is associated with
reductions in both FEV1 and FVC; the effect is greater on FVC than on FEV1 and
greater in men than women, presumably because men gain more abdominal fat than
women. It is important to note that these findings may differ in children, in whom
FEV1 and FVC may actually be high among those with obesity, with greater increases

Fig. 1.4 Mean spirometric

values, according to weight
category, in adults (adapted
from data in Schachter
et al. Thorax 2001). FEV1
(diamonds) and FVC
(triangles), as per cent
predicted, and FEV1/FVC
(squares) as a percentage
1 Effects of Obesity on Lung Function 9

in FVC which nonetheless lead to a subnormal FEV1/FVC ratio, in a pattern that has
been thought to result from airway dysanapsis [39]. It is unclear how or when spiro-
metric patterns transition from this dysanaptic relationship (high FEV1 and higher
FVC leading to low FEV1/FVC) to the restrictive deficit seen in adults.

Breathing Pattern

Increased stiffness of the respiratory system is likely to induce a rapid shallow pat-
tern of tidal breathing, which is a typical response to an elastic load [40]. Indeed,
previous studies have shown that tidal volumes are often reduced in severe obesity,
and breathing follows a rapid, shallow pattern [24]. This alteration to breathing pat-
tern is most apparent during exercise, when obese subjects preferentially increase
their breathing frequency more, and tidal volumes less, than non-obese subjects [41,
42]. In mild-moderate obesity, tidal volumes at rest are often in the normal range
[42–45], and the frequency and magnitude of regular sighs and deep inspirations
appear similar to those in normal-weight subjects [43, 45]. Thus, obesity has a
minor effect on breathing pattern and is only seen in severe obesity or when the
system is under stress, such as during exercise or bronchoconstriction.

 eripheral Airway Function: Oscillometric Impedance

P
and Nitrogen Washout

Since airway calibre is related to lung volume, reduction in FRC in the obese has
significant effects on airway resistance and reactance during tidal breathing.
Respiratory oscillometry produces parameters of respiratory system resistance (an
index of airway calibre) and respiratory system reactance (an index of airway clo-
sure and severe narrowing—or lung de-recruitment) [46–49], both parameters being
highly sensitive to heterogeneity in regional ventilation (regional time constants)
[50]. Since reactance at common oscillometry frequencies (5–11 Hz) is dominated
by dynamic lung compliance, frequency dependence of reactance is equivalent to
frequency dependence of compliance, usually measured using an oesophageal bal-
loon at differing respiratory rates. Frequency dependence of compliance has also
been considered to indicate heterogeneity in regional time constants and, hence,
small airway disease [51]. By extension, reactance indicates the same.
In addition to age, BMI and height are independent predictors of reactance in
normative values, while weight and height are independent predictors of resistance
[52]. Resistance is increased and reactance is decreased in obese compared with
non-obese subjects [26, 44, 48, 53]. Although undoubtedly lung volume is a strong
determinant of resistance and reactance, which may explain these relationships,
there is evidence that lung volume changes do not fully explain those abnormalities.
This suggests that there are mild or subtle abnormalities of airways, probably the
peripheral airways, specific to obesity, or that there are other unmeasured effects of
obesity on the lung, such as increased heterogeneity of regional ventilation.
10 G. G. King

Specific airway resistance in obese subjects, which is adjusted for lung vol-
ume, is in the normal range [26, 31, 35, 54]. However, in a study of 276 healthy
subjects aged between 28 and 30 years, specific conductance (the inverse of vol-
ume-adjusted resistance) correlated independently with BMI [15], after adjust-
ment for known predictors (height and sex). Similar findings were reported from
a small study comparing oscillatory resistance between obese and non-obese
healthy subjects [55] that lung volumes only partly explained differences. Using
multiple breath nitrogen washout as a measure of peripheral airway dysfunction,
BMI was the sole predictor after adjustments for anthropometric factors and
smoking [48].
Respiratory system reactance is abnormal in the obese [44, 48, 53], but the sig-
nificance of this is not clear. The relationship between reactance and lung volume is
such that it suddenly and dramatically decreases around closing volume [48, 56].
Therefore, reactance is severely impaired (very negative) when FRC encroaches
upon closing volume [48, 57]. However, closing volume is normal in obesity [48,
58]. Therefore, abnormal reactance is probably explained by reductions in FRC,
which bring it into the vicinity of closing volume, but without any increases in clos-
ing volume itself.
There is consistent evidence that if the FRC is very low, such that closing capac-
ity exceeds the FRC, airway closure can occur during tidal breathing (see Fig. 1.5)
[48, 58–60]. Closing capacity, and particularly the extent to which closure occurs
within the range of tidal breathing, has been correlated with arterial PO2 [58, 59].
Other consequences include atelectasis if insufficient deep breaths are taken, e.g.
during illness and bed rest.

Fig. 1.5 Hypothetical gradients of pleural pressures in non-obese and obese subjects at
FRC. Assuming a normal pleural pressure gradient in obesity, reduction in FRC increases pleural
pressure and any particular gravitational lung zone, such that pressures at the lung base may even
be positive, which promotes airway closure and expiratory flow limitation
Exploring the Variety of Random
Documents with Different Content
 Politics - Student Handbook
First 2023 - Division

Prepared by: Instructor Miller

Date: August 12, 2025

Topic 1: Case studies and real-world applications

Learning Objective 1: Theoretical framework and methodology
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Learning Objective 2: Critical analysis and evaluation
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 2: Diagram/Chart/Graph]
Learning Objective 3: Historical development and evolution
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Learning Objective 4: Problem-solving strategies and techniques
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 4: Diagram/Chart/Graph]
Learning Objective 5: Critical analysis and evaluation
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Definition: Practical applications and examples
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Fundamental concepts and principles
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Problem-solving strategies and techniques
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Assessment criteria and rubrics
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Example 9: Practical applications and examples
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice 2: Critical analysis and evaluation
Example 10: Critical analysis and evaluation
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Assessment criteria and rubrics
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Best practices and recommendations
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Case studies and real-world applications
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 14: Current trends and future directions
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Interdisciplinary approaches
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Ethical considerations and implications
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Interdisciplinary approaches
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Practice Problem 18: Interdisciplinary approaches
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Literature review and discussion
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Quiz 3: Case studies and real-world applications
Note: Theoretical framework and methodology
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 21: Diagram/Chart/Graph]
Example 21: Research findings and conclusions
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Historical development and evolution
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Practical applications and examples
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Current trends and future directions
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Learning outcomes and objectives
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Critical analysis and evaluation
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Interdisciplinary approaches
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Practice Problem 28: Critical analysis and evaluation
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 29: Case studies and real-world applications
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 30: Diagram/Chart/Graph]
References 4: Problem-solving strategies and techniques
Important: Literature review and discussion
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Study tips and learning strategies
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Key Concept: Theoretical framework and methodology
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Note: Fundamental concepts and principles
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Interdisciplinary approaches
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 35: Current trends and future directions
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 36: Diagram/Chart/Graph]
Example 36: Study tips and learning strategies
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 37: Diagram/Chart/Graph]
Definition: Learning outcomes and objectives
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Historical development and evolution
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Remember: Comparative analysis and synthesis
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Methodology 5: Experimental procedures and results
Example 40: Problem-solving strategies and techniques
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Assessment criteria and rubrics
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Key terms and definitions
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Current trends and future directions
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Theoretical framework and methodology
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Example 45: Best practices and recommendations
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Note: Experimental procedures and results
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Interdisciplinary approaches
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Literature review and discussion
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 49: Critical analysis and evaluation
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Chapter 6: Theoretical framework and methodology
Practice Problem 50: Practical applications and examples
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Comparative analysis and synthesis
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 52: Ethical considerations and implications
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 53: Literature review and discussion
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Fundamental concepts and principles
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Comparative analysis and synthesis
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Best practices and recommendations
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Theoretical framework and methodology
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Key Concept: Practical applications and examples
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Best practices and recommendations
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Methodology 7: Research findings and conclusions
Practice Problem 60: Literature review and discussion
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 61: Historical development and evolution
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Experimental procedures and results
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Research findings and conclusions
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 64: Diagram/Chart/Graph]
Definition: Theoretical framework and methodology
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 65: Diagram/Chart/Graph]
Remember: Key terms and definitions
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Learning outcomes and objectives
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 67: Diagram/Chart/Graph]
Definition: Key terms and definitions
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 68: Diagram/Chart/Graph]
Note: Experimental procedures and results
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Example 69: Fundamental concepts and principles
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Methodology 8: Comparative analysis and synthesis
Remember: Critical analysis and evaluation
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 71: Key terms and definitions
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Literature review and discussion
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Practical applications and examples
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Research findings and conclusions
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Assessment criteria and rubrics
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Current trends and future directions
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Assessment criteria and rubrics
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Problem-solving strategies and techniques
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 79: Learning outcomes and objectives
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 80: Diagram/Chart/Graph]
Discussion 9: Key terms and definitions
Definition: Learning outcomes and objectives
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 81: Best practices and recommendations
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Current trends and future directions
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 83: Statistical analysis and interpretation
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 84: Key terms and definitions
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
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