2.6 4.

Systematic Review

Smoking Cessation on
Periodontal and Peri-Implant
Health Status: A Systematic
Review

Mario Caggiano, Roberta Gasparro, Francesco D’Ambrosio, Massimo Pisano,

Maria Pia Di Palo and Maria Contaldo

Special Issue
Advances in Periodontal and Peri-Implant Tissues Health Management
Edited by
Dr. Federica Di Spirito and Dr. Alessandra Amato

https://doi.org/10.3390/dj10090162
 dentistry journal
Systematic Review
Smoking Cessation on Periodontal and Peri-Implant Health
Status: A Systematic Review
Mario Caggiano 1 , Roberta Gasparro 2 , Francesco D’Ambrosio 1, * , Massimo Pisano 1 , Maria Pia Di Palo 1
and Maria Contaldo 3

1 Department of Medicine, Surgery and Dentistry “Schola Medica Salernitana”, University of Salerno,
Via S. Allende, 84081 Baronissi, Italy
2 Department of Neuroscience, Reproductive Science and Dentistry, University of Naples Federico II,
80131 Naples, Italy
3 Multidisciplinary Department of Medical-Surgical and Odontostomatological Specialities,
University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
* Correspondence: [email protected]

Abstract: Since smoking is considered among the main risk factors for the onset and progression
of periodontitis and peri-implantitis, the present systematic review aimed to evaluate the effect of
smoking cessation on clinical, radiographic, and gingival crevicular periodontal parameters around
natural teeth and dental implants in ex-smokers compared to current and non-smokers. The study
protocol was developed based on the PRISMA guidelines, the research question was formulated
according to the PICO model, and the literature search was conducted through PubMed/MEDLINE,
Cochrane library, and BioMed Central databases. From the 916 title/abstracts initially identified,
seven articles were included in the present systematic review and assessed for quality through the
Citation: Caggiano, M.; Gasparro, R.;
ROBINS-I tool. Reported findings on clinical and crevicular periodontal parameters around natural
D’Ambrosio, F.; Pisano, M.; Di Palo, teeth were contrasting when comparing ex-smokers to current and non-smokers; thus, individualized
M.P.; Contaldo, M. Smoking recommendations for previous smoker periodontal patients are currently lacking. No data on
Cessation on Periodontal and radiographic parameters were retrieved. Similarly, data on periodontal parameters around dental
Peri-Implant Health Status: A implants were not available, highlighting the need for focused investigations assessing the role of
Systematic Review. Dent. J. 2022, 10, both smoking habit and cessation on peri-implant health status and responsiveness to treatment.
162. https://doi.org/10.3390/
dj10090162 Keywords: smoking cessation; smoking cessations; tobacco; tobacco use; cigarette smoking; smokers;
Academic Editors: Federica Di ex-smokers; non-smokers; periodontitis; periodontal disease; peri-implantitis; peri-implant disease
Spirito, Alessandra Amato and
Patrick R. Schmidlin

Received: 7 August 2022

1. Introduction
Accepted: 27 August 2022
Published: 31 August 2022
Periodontitis is a chronic inflammatory disease associated with the presence of mi-
croorganisms and sustained by host-mediated immune-inflammatory response [1–4], con-
Publisher’s Note: MDPI stays neutral
sequently establishing itself within periodontal tissues and causing their destruction with
with regard to jurisdictional claims in
clinical attachment loss and bone loss [5–8] until tooth loss [9]. The inflammation of peri-
published maps and institutional affil-
odontal tissues, along with the dysbiotic phenomena of the periodontal microbiome [10–13],
iations.
would also appear to play a role in the pathogenesis of systemic conditions and disorders of
degenerative inflammatory and neoplastic nature [14–19], which, in turn, could influence
the onset and, more importantly, the progression of periodontitis. The rate of progression of
Copyright: © 2022 by the authors.
periodontitis is primarily estimated through both direct clinical and radiographic evidence
Licensee MDPI, Basel, Switzerland. of periodontal destruction assessed over time and indirect evidence related to biofilm accu-
This article is an open access article mulation. It is affected by the effect of glycemia and smoking, recognized as periodontitis
distributed under the terms and grade modifiers [20]. In particular, smoking is also considered among the main risk factors
conditions of the Creative Commons for the onset of periodontitis [21,22]. Similarly, peri-implantitis, which is a microbially initi-
Attribution (CC BY) license (https:// ated destructive inflammation of the tissues surrounding dental implants which eventually
creativecommons.org/licenses/by/ determines bone loss until implant loss [23–29], shares common etiopathogenic pathways
4.0/). with periodontitis [30] and is also negatively affected by habitual smoking [31,32].

Dent. J. 2022, 10, 162. https://doi.org/10.3390/dj10090162 https://www.mdpi.com/journal/dentistry

Dent. J. 2022, 10, 162 2 of 18

However, the biological and molecular mechanisms underlying the negative associa-
tion between smoking and the health status of periodontal and peri-implant tissues has
not yet been defined; thus, at the current state of knowledge, there are no preventive or
therapeutic approaches in periodontal practice individualized for periodontal subjects who
smoke. Coherently, smoking cessation may be regarded as the best feasible intervention for
reducing the risk of onset and progression of both periodontitis and peri-implantitis [31].
Although multiple pharmacological, non-pharmacological, and combined approaches
have been developed for smoking cessation to achieve short-term smoking abstinence
and relapse avoidance, as a part of inter-professional primary and secondary prevention
strategies [4,33–35], the impact of smoking cessation on periodontal and peri-implant health
status has been rarely investigated.
Therefore, the present systematic review aimed to assess the effect of smoking cessation
on clinical, radiographic, and gingival crevicular periodontal parameters around natural
teeth and dental implants in ex-smokers compared to non-smokers and current smokers.

2. Materials and Methods

2.1. Study Protocol
The present study was conducted under the Preferred Reporting Items for Systematic
Reviews and Meta-analyses (PRISMA) statement [36,37], available at http://www.prisma-
statement.org/ (accessed on 15 July 2022).
Question formulation, search strategy, and study selection definition were performed
according to the PICO model [38] (https://linkeddata.cochrane.org/pico-ontology (ac-
cessed on 15 July 2022)). The question of the present systematic review was “Does smoking
cessation positively affect periodontal and peri-implant health status?” focusing on:
P—Population: ex-smokers (traditional “TS” and Heat-Not-Burn “HNB” tobacco and
electronic nicotine delivery systems “E-cigs” smokers);
I—Intervention: smoking cessation;
C—Comparison: smoking habit/no previous history of tobacco smoke (current smok-
ers “CS”/non-smokers “NS”);
O—Outcome: clinical, radiographic, and inflammatory periodontal parameters around
natural teeth and implants.

2.2. Search Strategy

Articles published and in press in the English language were electronically searched
by two independent reviewers (F.D.A., M.P.D.P.) until 15 July 2022, with no restrictions
concerning dates of coverage and publication status, across MEDLINE/PubMed, Cochrane
library, and BioMed Central databases by applying the following keywords:
1. Periodontal disease OR periodontitis OR peri-implant disease OR peri-implantitis
OR tooth loss OR dental implant OR implant loss OR clinical attachment loss OR probing
depth OR plaque index OR gingival index OR bleeding on probing OR marginal bone loss
OR TNF-a OR IL-1b OR IL-4 OR IL-6 OR IL-8 OR IL-9 OR IL-10 OR IL-13 OR IFN-y OR
MMP-1 OR MMP-8 OR RANKL OR OPG).
AND:
2. Smoking cessation OR stop smoking OR quit smoking OR cessation of smoking OR
stopping smoking OR quitting smoking OR ex-smokers OR exsmokers).
Reference lists of eligible articles were also screened, and a further additional literature
search was conducted.

2.3. Study Selection

Two reviewers (F.D.A., M.P.D.P) independently performed study selection, involving
a third reviewer (M.C.) in case of discrepancies.
Title and abstract selection was performed for all papers identified through the elec-
tronic literature search and potentially relevant full-texts were also retrieved by contacting
the authors.
Dent. J. 2022, 10, 162 3 of 18

Full texts were screened for potentially eligible and ambiguous abstracts according to
the inclusion/exclusion criteria shown in Table 1.

Table 1. Inclusion and exclusion criteria related to source, characteristics, population, intervention,
comparison, and outcome(s) of relevant studies.

Study Inclusion Criteria Exclusion Criteria

Characteristics
Type Clinical Narrative reviews
Books and chapters
Conference papers
Oral communications
In vitro
Pre-clinical in vivo
Design Cross-sectional Case series
Case-control Case reports
Retrospective
Prospective
Randomized Clinical Trials (RCT)
Sample size ≥50 <50
Population Periodontal subjects Periodontally healthy subjects
Age ≥18 years old <18 years old
Gender No restrictions No restrictions
Characteristics Ex-smokers Smokers
Non-smokers
Pregnancy; lactation
Comorbidities Any Neoplastic disease
Medication-related osteonecrosis of the jaws
Systemic disease affecting bone metabolism or
periodontal/peri-implant disease
Non-surgical/surgical periodontal treatment (within <3
months)
Radiations (head and neck)
Antibiotics, corticosteroids (within 3 months)
Drugs affecting bone metabolism
Non-surgical/surgical periodontal
Treatments
treatment (within ≥3 months)
Smoking cessation
Intervention No discontinuing tobacco smoking
(ex-smokers)
No smoking cessation
Comparison (current smokers)
No smoking habit
(non-smokers)
Dent. J. 2022, 10, 162 4 of 18

Table 1. Cont.

Study Inclusion Criteria Exclusion Criteria

Outcome(s) Periodontal and peri-implant status Endodontic-periodontal lesions
Endodontic lesions
Failure of osseointegration
Clinical Attachment Level (CAL)
Clinical periodontal
Periodontal Probing Depth (PPD)
parameters
Plaque Index (PI)
Gingival Index (GI)
Bleeding on Probing (BOP)
Tooth loss; implant loss
Radiographic
periodontal
parameters
Radiographic bone loss around natural
teeth (RBL)
Marginal bone loss around dental
implants (MBL)
Other
Gingival crevicular (GC) inflammatory
periodontal
mediators
parameters

2.4. Data Collection and Synthesis

Three independent reviewers (F.D.A., M.P.D.P, M.C.) extracted data twice and collected
them in a dedicated form based on those proposed for RCT and non-RCT intervention
reviews [39] (https://dplp.cochrane.org/data-extraction-forms (accessed on 15 July 2022)).
No further processes were performed to obtain or confirm data from the investigators.
Data collected for the studies included in the present systematic review concerned
study source (first author, year of publication and journal, funding) and design, partic-
ipants (number, gender, and age; comorbidities, smoking habit duration), intervention
(smoking cessation duration), comparison (current smokers/non-smokers), and periodon-
tal outcomes around natural teeth and implants (clinical and radiographic indices, gingival
crevicular inflammatory mediator levels, and conclusions).
Descriptive statistical analyses were conducted using Microsoft Excel software 2019
(Microsoft Corporation, Redmond, WA, USA).

2.5. Quality Assessment

Study quality assessment was performed through the ROBINS-I (“Risk Of Bias In
Non-randomized Studies of Interventions”) tool, based on biases due to confounding,
participant selection, classification of interventions, deviations from intended interventions,
missing data, outcome measurements, and selection of the reported result [40].

3. Results
3.1. Study Selection
In total, 1086 titles/abstracts were initially retrieved through the electronic search,
specifically 897 from MEDLINE/PubMed, 3 from BioMed Central databases, and 186 from
the Cochrane library, respectively. Duplicates were eliminated and 916 potentially pertinent
title/abstracts were identified, of which24 records concerned periodontal health conditions
around natural teeth and around dental implants.
Dent. J. 2022, 10, 162 5 of 18

After title/abstract screening, 17 records were excluded because they were not perti-
nent, including 10 reviews [41–50], 4 studies without clinical data, and 3 studies that did
not meet inclusion criteria [51–57], as shown in Figure 1 (and synthesized in the table of
the studies excluded with reasons for exclusion available as Supplementary Materials).
Subsequently, seven full-texts were screened which did not require contacting the authors.
Based on eligibility criteria, seven studies [58–64] were finally included in the present
systematic review, as illustrated in Figure 1.

Figure 1. PRISMA 2020 flow diagram for new systematic reviews which included searches of
databases and registers only.

3.2. Study Characteristics and Descriptive Data Analysis

Descriptive analysis of the studies included in the present systematic review is detailed
in Table 2.
Dent. J. 2022, 10, 162 6 of 18

Table 2. Data extracted and collected from the studies included in the present systematic review:
general information; methods; periodontal outcomes; conclusion(s).

Periodontal Parameters Around

Included Natural Teeth
Methods Conclusion(s)
Studies Statistically Significant
(p < 0.05)
Population Clinical
Participants (n.) Clinical Attachment Level (CAL)
Age (y.o.)
Male/female (M/F) Periodontal Probing Depth (PPD)
Periodontal status
Comorbidities Bleeding on Probing (BOP)
Smoking habit duration (years)
Smoking habit characteristics: traditional
Gingival Index (GI)
Author tobacco;
Year
Heat-Not-Burn tobacco; electronic
[Reference] Plaque Index (PI)
nicotine delivery systems (E-cigs);
Journal
Study design Cigarettes or equivalent n./day
Intervention Tooth loss
Smoking cessation (duration) Implant loss
(ex-smokers)
Comparison Radiographic
Ongoing smoking habit (smokers) Radiographic bone loss (RGB)
No smoking habit (non-smokers)
Gingival crevicular (GC)
Procedure(s)
inflammatory mediators
Non-surgical periodontal treatment Any
Surgical periodontal treatment
Study participants (n.57) Clinical
Age (35.19 +/− 2.23) CAL
Male/female (39/18) GI
Periodontal subjects PI
Comorbidities: MD GI was significantly higher
Karaslaan et al., Radiographic among E-cigs smokers and
2020 [58] ex-smokers compared to
Aust. Dent. J. Smoking habit duration: MD MD tobacco smokers
Case-control Smoking habit characteristics: tobacco GI was significantly lower
study smokers (13.95 +/−3.01 years) among E-cigs smokers
compared to ex-smokers
E-cigs smokers (2.32 +/− 0.75 years) GC Inflammatory mediators
Interleukin-8
Intervention Tumor Necrosis Factor-alfa
Smoking cessation (duration MD) Glutathione peroxidase
8-hydroxydeoxyguanosine
Dent. J. 2022, 10, 162 7 of 18

Table 2. Cont.

Periodontal Parameters Around

Included Natural Teeth
Methods Conclusion(s)
Studies Statistically Significant
(p < 0.05)
Comparison

- tobacco smokers with periodontitis

- E-cigs smokers with periodontitis

- ex-smokers with periodontitis

Procedure(s)
Non-surgical periodontal treatment
Study participants (n.13551) Clinical
Age (divided into range of 10 years) CPI divided into 0–4 points
Male/female (5715/7836) 0 for healthy periodontal tissue
Periodontal status: MD 1 (bleeding periodontal tissue)
Comorbidities: MD 2 (gingival biofilm)
3 (3.5 ≤ pocket depth < 5.5 mm)
Smoking habit duration: MD 4 (pocket depth ≥ 5.5 mm).
Smoking habit characteristics: Tobacco A score of 3–4 denotes periodontal
smokers disease
E-cigs smokers

Jeong et al., Radiographic Periodontitis rate was

2020 [59] significantly higher in
Intervention MD
J. Periodont. tobacco smokers and
Evaluation of periodontal diseases E-cigs smokers compared
Case-control
among the group to ex-smokers and
study
GC Inflammatory mediators smokers

Comparison MD

- non-smokers

- tobacco smokers

- E-cigs

- ex-smokers

Procedure(s)
Non-surgical periodontal treatment
Dent. J. 2022, 10, 162 8 of 18

Table 2. Cont.

Periodontal Parameters Around

Included Natural Teeth
Methods Conclusion(s)
Studies Statistically Significant
(p < 0.05)
Study participants (n.705) Clinical
Age (35–65 y.o.) CAL
Male/female (341/364) PI
Periodontal status: MD BOP
Comorbidities: MD PPD
Smoking habit duration: Radiographic
in ex-smokers (28.6 +/− 12.7 years) and
MD
in smokers (35.5 + 7 − 14.8 years)
Costa et al., Smoking habit characteristics: Cumulative smoking
2013 [60] non-smokers exposure and duration of
J. Oral Sci. smoking cessation were
tobacco smokers GC inflammatory mediators
Cross-sectional significantly associated
study ex-smokers MD with periodontitis
Intervention
Smoking cessation (duration MD)
Comparison

- non-smokers

- smokers

- ex-smokers

Study participants (n.142) Clinical

Age (MD) CAL
Male/female (MD) BOP
Periodontal status: MD PPD
Comorbidities: diabetes PI
Smoking habit duration: MD Radiographic
Smoking habit characteristics:
MD
non-smokers
tobacco smokers Smoking negatively affects
Costa et al.,
periodontitis and, in
2019 [61] ex-smokers GC inflammatory mediators
particular, smoking
J. Periodont.
MD cessation positively affects
Cohort study
periodontitis
Intervention
Smoking cessation (6 years)
Comparison

- smokers

- non-smokers

- ex-smokers
Dent. J. 2022, 10, 162 9 of 18

Table 2. Cont.

Periodontal Parameters Around

Included Natural Teeth
Methods Conclusion(s)
Studies Statistically Significant
(p < 0.05)
Study participants (n.23376) Clinical
Age (non-smokers, 50.3 ± 8.8;
ex-smokers, 50.5 ± 9.0; smokers, 47.2 ± Tooth loss
8.7)
Male/female (9032/14,344)
Periodontal status: MD Radiographic
Comorbidities: diabetes and
MD
hypertension Smoking habit had a
Smoking habit duration: MD GC Inflammatory mediators stronger association with
Dietrich et al.,
tooth loss in M > F and in
2015 [62] Smoking habit characteristics:
MD younger > older subjects
J. Dent. Res. non-smokers Smoking cessation was
Prospective
tobacco smokers associated with a
cohort study
reduction in tooth loss risk
ex-smokers
in approximately 20 years
Intervention
Smoking cessation (duration MD)
Comparison

- non-smokers

- tobacco smokers

- ex-smokers

Study participants (n.122) Clinical

Age (MD) GI
Male/female (122/0) PI
Periodontal status: MD No significant differences
Comorbidities: MD Radiographic in GC Matrix
Metalloproteasis-8 and
MD Matrix Metalloproteasis-9
Liu et al., Smoking habit duration: MD were detected between
2015 [63] smokers, ex-smokers (for 1
Smoking habit characteristics: n.13 year), and non-smokers
J. Perio. Res. GC inflammatory mediators
non-smokers This 1-year prospective
Prospective
study n.11 ex-smokers Matrix Metalloproteasis-8 smoking cessation study
shows GC Interleukin-1b
n.9 smokers Matrix Metalloproteasis-9
could have a positive
n.6 oscillators Interleukin-1b relationship with nicotine
and cotinine levels in
Cotinine
saliva
Intervention Nicotine
Smoking cessation (1 year)
Dent. J. 2022, 10, 162 10 of 18

Table 2. Cont.

Periodontal Parameters Around

Included Natural Teeth
Methods Conclusion(s)
Studies Statistically Significant
(p < 0.05)
Comparison

- non-smokers (n.13)

- ex-smokers (n.11)

- smokers (n.9)

- oscillators (n.6)

Study participants (n.226) Clinical

Age (>18 years) PI
Male/female (90/136) GI
Periodontal status: MD PD
Comorbidities: MD
Radiographic
Smoking habit duration: MD MD Higher PI was found in
smokers (2.78 ± 0.92)
Smoking habit characteristics: compared to non-smokers
Beklen et al., non-smokers (1.0 ± 0.6) and ex-smokers
2021 [64] tobacco smokers GC Inflammatory mediators (1.1 ± 0.8)
TobInduc. Dis. PD values were
ex-smokers MD
Cross-sectional significantly (p < 0.05)
study Intervention higher in smokers
Smoking cessation (duration MD) (5.6 ± 1.9) compared to
non-smokers (1.6 ± 0.8)
Comparison and ex-smokers (2.4 ± 1.3)

- non-smokers

- tobacco smokers

- ex-smokers

Abbreviations: current smokers, CS; traditional tobacco smokers, TS; electronic cigarette or electronic cigarette
smokers, E-cigs; non-smokers, NS; years old, y.o.; missing data, MD; Probing Depth, PD; clinical attachment
loss, CAL; Plaque Index, PI; Bleeding on Probing, BOP; Gingival Index, GI; Community Periodontal Index, CPI;
gingival crevicular, GC.

The extracted data, synthesized in Table 3, all concerned periodontal parameters

around natural teeth and none of the data concerned periodontal parameters around
dental implants. Radiographic periodontal parameters were not described in the records
retrieved from the literature. Due to the heterogeneity of the included studies and the lack
of randomized controlled trials, it was not possible to conduct a metanalysis.
Dent. J. 2022, 10, 162 11 of 18

Table 3. Synthesis of the periodontal parameters around natural teeth reported in the studies included
in the present systematic review.

Periodontal Parameter Main Result(s) Author, Year

Mean CAL values and the percentage of sites with a CAL
value ≥ 5 mm and tooth loss were lower in ex-smokers and Costa et al., 2013 [60]
non-smokers compared to smokers;
Mean CAL values and the percentage of sites with a CAL
CAL
value ≥ 5 mm and tooth loss were lower in ex-smokers and Costa et al., 2019 [61]
non-smokers compared to smokers;
Mean CAL values were not significantly different among
Karaaslan et al., 2020 [58]
ex-smokers, smokers, and non-smokers.
Mean PI values were lower in ex-smokers and non-smokers
Costa et al., 2013 [60]
compared to smokers;
Mean PI values were not significantly different among ex-smokers,
Liu et al., 2015 [63]
smokers, and non-smokers;
Mean PI values were not significantly different among ex-smokers,
Karaaslan et al., 2020 [58]
PI smokers, and non-smokers;
Mean PI values were lower in ex-smokers (1.1 ± 0.8) and
Beklen et al., 2021 [64]
non-smokers (1.0 ± 0.6) compared to smokers (2.78 ± 0.92);
Mean PI values were lower in ex-smokers and non-smokers
compared to smokers (PI values for smokers > ex-smokers > Costa et al., 2019 [61]
non-smokers).
The mean number of sites with BOP was significantly lower in
Costa et al., 2013 [60]
smokers compared to ex-smokers and non-smokers;
BOP
The mean number of sites with BOP was significantly lower in
Costa et al., 2019 [61]
smokers compared to ex-smokers and non-smokers.
Mean PD values were not significantly different among ex-smokers,
Karaaslan et al., 2020 [58]
smokers, and non-smokers;
Mean PD values and he percentage of sites with a PD ≥ 5 mm were
Costa et al., 2013 [60]
lower in ex-smokers and non-smokers compared to smokers;
PD Mean PD values and the percentage of sites with a PD ≥ 5 mm
were lower in ex-smokers (2.4 ± 1.3) and non-smokers (1.6 ± 0.8) Beklen et al., 2021 [64]
compared to smokers (5.6 ± 1.9);
Mean PD values were not significantly different among ex-smokers,
Liu et al., 2015 [63]
smokers, and non-smokers.
Mean GI values were not significantly different among ex-smokers,
Liu et al., 2015 [63]
smokers, and non-smokers at baseline;
GI values were lower in ex-smokers (1.9 ± 1.0) and non-smokers
Beklen et al., 2021 [64]
GI (0.5 ± 0.4) compared to smokers (2.5 ± 0.5);
GI values were significantly higher in ex-smokers and electronic
cigarette smokers compared to smokers and were significantly Karaaslan et al., 2020 [58]
lower in electronic cigarette smokers compared to ex-smokers.
Tooth loss was lower in ex-smokers and non-smokers compared
Costa et al., 2019 [61]
to smokers;
Tooth loss was significantly higher in ex-smokers and smokers
Costa et al., 2013 [60]
Tooth loss compared to non-smokers;
A negative dose-dependent association between cigarette smoking,
smoking cessation, and number of natural teeth was found Dietrich et al., 2015 [62]
at baseline.
Dent. J. 2022, 10, 162 12 of 18

Table 3. Cont.

Periodontal Parameter Main Result(s) Author, Year

GC TNF-a levels were significantly higher in smokers
Tumor Necrosis
(4.20 +/− 0.14) compared to electronic cigarette smokers; no data Karaaslan et al., 2020 [58]
Factor-alfa (TNF-a)
concerning ex-smokers.
GC IL-1b was significantly lower (p = 0.007) in ex-smokers,
Interleukin-1b
non-smokers, and oscillators compared to smokers at 2-month Liu et al., 2015 [63]
(IL-1b)
follow-up.
GC IL-8 levels were significantly higher in ex-smokers
Interleukin-8
(70.47 +/− 2.76) and electronic cigarette smokers compared Karaaslan et al., 2020 [58]
(IL-8)
to smokers.
Periodontal disease was more prevalent in electronic cigarette
CPI smokers and tobacco smokers compared to non-smokers; no data Jeong et al., 2020 [59]
concerning ex-smokers.
Matrix metalloproteasis-8 GC MMP-8 and MMP-9 were not significantly different between
Liu et al., 2015 [63]
and -9 (MMP-8 -9) smokers and ex-smokers (for 1 year).
GC glutathione peroxidase levels were significantly higher in
Glutathione peroxidase ex-smokers compared to tobacco smokers, electronic cigarette Karaaslan et al., 2020 [58]
smokers, and ex-smokers.
Abbreviations: traditional tobacco smokers, TS; electronic cigarette or electronic cigarette smokers, E-cigs; non-
smokers, NS; years old, y.o.; missing data, MD; Probing Depth, PD; clinical attachment loss, CAL; Plaque Index,
PI; Bleeding on Probing, BOP; Gingival Index, GI; Community Periodontal Index, CPI; gingival crevicular, GC.

3.3. Quality Assessment

The studies currently considered were assessed for quality [40], as shown in Table 4.
In detail, Jeong et al., 2020 [59], used a different measurement parameter for periodontal
disease, the CPI, that might be considered a bias for measurement of outcomes.

Table 4. Risk of bias for the studies included in the systematic review: ‘Yes’ indicating a low risk
of bias, ‘Probably yes’ indicating a moderate risk of bias, ‘Probably no’ indicating a serious risk
of bias, ‘No’ indicating a critical risk of bias, and ‘No information’ indicating that no information
was available.

Bias in Bias Due to

Bias in Bias Due to
Bias Due to Bias in Selection Measurement Deviations from Bias Due to
Studies Measurement of Selection of the
Confounding of Participants Classification of Intended Missing Data
Outcomes Reported Result
Interventions Interventions
Costa et al.,
Yes Yes Yes Yes Yes Yes Yes
2013 [60]
Costa et al.,
Probably yes Yes Yes Yes Yes Yes Yes
2019 [61]
Karaaslan et al.,
Yes Yes Yes Yes Yes Yes Yes
2020 [58]
Liu et al.,
Probably no Yes Yes Yes Yes Yes Yes
2015 [63]
Dietrich et al.,
Yes Yes Yes Yes Yes Yes Yes
2015 [62]
Beklen et al.,
Yes Yes Yes Yes Yes Yes Yes
2021 [64]
Jeong et al.,
Probably no Yes Yes Yes Yes Probably yes Yes
2020 [59]
Risk of bias
Serious Low Low Low Low Moderate Low
judgements

4. Discussion
It has long been known that smoking habit increases the risk of periodontitis on-
set [31], by up to 85% as per Leite et al. [41], and progression [9]. In addition, smoking
has been commonly regarded as potentially detrimental for dental implant survival and
Dent. J. 2022, 10, 162 13 of 18

success [5,8,23,65] and is considered as a negative predictor for tooth and dental implant
loss [32,65]. Therefore, the present systematic review aimed to evaluate the effect of smok-
ing cessation on clinical, radiographic, and gingival crevicular periodontal parameters
around natural teeth and dental implants in ex-smokers compared to non-smokers and
current smokers.
Even so, the seven studies included in the present systematic review only evaluated
the periodontal state around natural teeth after periodontal treatment, while none of the
studies included the state around implants. This finding suggests the need for extensive
additional research, especially considering that very little evidence is currently available on
the role of smoking habit on peri-implant tissue health [24,65,66]. Indeed, conflicting results
have been reported in the literature. Specifically, Koldsland et al. [67] and Roos-Jansåker
et al. [68,69] failed to detect a significant association between smoking and peri-implant
disease prevalence and implant loss, respectively.
Data on former and current conventional tobacco smokers were collected and an-
alyzed; those concerning electronic devices were included but qualitatively analyzed
separately. Conversely, no data concerning Heat-Not-Burn tobacco product smokers have
been retrieved, though increasingly common [32], probably due to their recent use. In
addition, findings from the so-called “oscillators”, i.e., previous smokers with relapse, were
excluded from the investigated population to reduce the risk of bias due to the selection
of participants.
In detail, periodontal tissue destruction around natural teeth was known to be greater
in current smokers [70] compared to non-smokers and ex-smokers, as also confirmed by
Costa et al. [60,61], even though Karaaslan et al. [58] found similar CAL values and a
similar percentage of sites with CAL values ≥ 5 mm among smokers, non-smokers, and
ex-smokers. As a counterpart, tooth loss as a consequence of periodontitis had a higher rate
of occurrence in current and ex-smokers [60,61] compared to non-smokers, especially in
younger males [62]. However, Costa et al. recently found that the amount of teeth loss due
to periodontitis was higher in ex-smokers compared to current smokers and non-smokers;
this observation may be likely ascribable to the higher mean age of the ex-smokers [61].
Notably, a negative dose-dependent association between smoking habit and the number
of residual natural teeth, declining after approximately 20 years from smoking cessation,
was described by Dietrich et al. [62]. This timeframe may, if validated, aid in estimating
periodontitis onset odds ratio decline in ex-smokers, and accordingly guide maintenance
recall interval planning. Radiographic periodontal parameters assessing alveolar bone
loss were described neither around natural teeth nor dental implants in ex-smokers, so
no comparison could be made with radiographic findings registered as better or worse in
smokers compared to non-smokers [16,30,32]. However, considering that CAL and bone
loss quantify historical tissue destruction [4,9,21,22], significant differences should not be
expected between smokers and subjects quitting smoking recently, while an improvement
in PD values may be anticipated.
Accordingly, Costa et al. [60] and Beklen et al. [64] reported lower periodontal probing
depth values and a lower percentage of sites with a PD ≥ 5 mm in ex-smokers and non-
smokers compared to current smokers. No differences in PD values were in anyway
observed by Karaaslan et al. and Liu et al. [58,63] in relation to a smoking habit or smoking
cessation. Such contrasting results should also be evaluated in conjunction with individual
periodontal inflammatory indices, potentially affecting gingival hypertrophy, and with
local causative factors such as biofilm also supporting superficial tissue edema.
In detail, a significantly lower mean number of sites with BOP+ was described in
smokers vs. ex-smokers and non-smokers [60,61], likely due to the vasoconstriction observ-
able within gingiva and, conceivably, peri-implant mucosa, secondary to both traditional
and Heat-Not-Burn tobacco products [32,62,71]. Furthermore, GI values were reported to
be higher in ex-smokers compared to current smokers [58,63,64].
Beklen et al. [60] and Costa et al. [64] described higher PI values in smokers compared
to ex-smokers and non-smokers. This finding, combined with the hypothesis that nicotine
Dent. J. 2022, 10, 162 14 of 18

may favor the proliferation of A. actinomycetemcomitans and P. gingivalis which are suspected
periodontal pathogens species, may support the wider periodontal destruction observed
in smokers. Similarly, a greater microbial load, particularly composed of periodontal
pathogens, has been detected in peri-implant sulci in smokers [28,65]. Given that peri-
implant biofilm shares microbial species with periodontal ones, both in physiological
and pathological conditions, it has been accordingly proposed that residual teeth and
periodontal tissues may act as potential reservoirs of pathogens which eventually colonize
peri-implant tissues in subjects with active periodontitis, especially if smokers [28,65,72].
However, in contrast, Karaaslan et al. [58] and Liu et al. [63] did not find significant
differences in plaque amounts between current, former, and non-smokers; therefore, no
definitive conclusions could be drawn.
It is worth noting that even if the smoking habit has also been described to negatively
affect periodontal therapy outcomes in smokers [73], considering clinical, radiographic,
and crevicular parameters around both natural teeth and dental implants [32], no relevant
data were currently extracted concerning ex-smokers undergoing periodontal treatment.
Both cumulative smoking exposure and duration of smoking cessation were only
reported to be significantly associated with periodontitis by Costa et al. [60,61]. However,
a paucity of evidence exists to describe the role of the number of cigarettes/day and the
time interval since smoking cessation on the potential improvement of periodontal and
peri-implant parameters. Similarly, the estimate of the reduction is still debated regarding
former vs. current and non-smokers and the risk of periodontitis and peri-implantitis onset
and worsening; such an estimate has been computed, instead, for smoking cessation in
relation to life expectancy, which increases by 10, 9, and 6 years for those who quit smoking
at 30, 40, and 50 years [74], respectively. In this regard, Alharti et al., 2018 [57], reported a
higher prevalence of periodontitis of up to 35% in smokers, compared to 19% in previous
smokers and 13% in non-smokers, and estimated a reduction in the risk of periodontitis
progression of 3.9% for each year of smoking cessation.
The results of the present study, that turned out to be so contrasting, could be ex-
plained by the long-standing debate on the pathogenic role of smoking in the onset and
progression of periodontitis and peri-implantitis. Indeed, the causative role of smoking in
the genesis of these diseases, which are microbially associated inflammations, has long been
supported by evidence revealing an intrinsic chemical and mechanical capacity of smoking
to compromise periodontal health status. In contrast, multiple pieces of evidence suggested
that it was instead the poor oral care of smokers, and thus the accumulation of biofilm, that
determined the onset and progression of periodontitis. At the current state of knowledge,
smoking has been found capable of reducing host defenses and indirectly facilitating the
action of virulence factors of suspected pathogenic species within the biofilm. Smoking
has been shown to induce the production of proinflammatory cytokines and enzymes with
a destructive effect within periodontal tissues in addition to facilitating, as mentioned
above, colonization by pathogenic species [75–77]. In detail, crevicular proinflammatory
biomarkers have been presently found and recorded by several authors since they may be
useful tools for diagnostic and prognostic purposes in both periodontal and peri-implant
disease. In particular, proinflammatory cytokines such as Tumor Necrosis Factor-alpha and
Interleukin-1b are secreted by macrophages in response to lipopolysaccharide contained in
bacterial membranes. Consequently, macrophages can activate osteoclastogenesis, causing
bone resorption, and induce fibroblast apoptosis, contributing to clinical attachment loss.
Crevicular IL-1b and TNF-a levels detected in current smokers were found to be signifi-
cantly higher, particularly in traditional tobacco smokers vs. E-cigs smokers [32], compared
to former and non-smokers.
The main limitations of the present systematic review rely upon the few relevant
articles identified from the literature search, including the evaluation of periodontal out-
comes in ex-smokers. In addition, no data could be retrieved regarding clinical periodontal
parameters around dental implants or radiographic parameters around the dental elements
and around the implants. The data extracted and analyzed were severely lacking and
Dent. J. 2022, 10, 162 15 of 18

contrasting and were derived from studies that included smokers with different smoking
habits and smoking cessation durations, precluding comparison among the groups. In most
of the studies, the duration of previous smoking habits and the type of smoking, as well as
the duration of smoking cessation, were often not specified. Moreover, data concerning
periodontal outcomes in ex-smokers of Heat-Not-Burn tobacco products were not found,
probably due to the recent introduction of these tobacco systems. Therefore, data were thus
found to be very deficient, and it was not possible to perform the meta-analysis.
Nevertheless, the presented results clearly highlight the need for further investigations
assessing the potentially beneficial role of smoking cessation on periodontal conditions
around teeth and dental implants. In more detail, future research may identify a time
cut-off for detecting such improvements, estimate their magnitude in relation to the time
interval from smoking cessation, and thus favor personalized planning of initial and
maintenance periodontal treatments in ex-smokers. Moreover, future investigations may
also point out the odds ratio of periodontitis and peri-implantitis onset in ex-smokers
compared to current smokers and non-smoking periodontally healthy subjects, thus im-
proving periodontitis and peri-implantitis prevention. A similar estimate might also be
computed for the progression of such diseases in periodontal subjects. Personalized pre-
vention strategies may be even more relevant in those subjects considered at higher risk
of periodontitis and peri-implantitis onset and progression, such as those suffering from
comorbidities [4,10,14,15,30,33,78–80], especially diabetes [17].

5. Conclusions
A paucity of evidence describes the effect of smoking cessation on clinical, radio-
graphic, and crevicular periodontal parameters around natural teeth. Even fewer data
describe the effect of smoking cessation on periodontal treatment outcomes; therefore,
individualized recommendations for periodontal patients who are smokers or ex-smokers,
with or without comorbidities, are currently lacking. Thus, further investigation should
point out the role of smoking cessation on periodontally healthy subjects, as well as on
those suffering from periodontitis, aiding in periodontal treatment planning in active and,
above all, maintenance phases.
No data were retrieved concerning periodontal parameters around dental implants,
highlighting the need for focused investigations assessing the role of both smoking habit
and cessation on peri-implant health status and responsiveness to treatment.

Supplementary Materials: The following supporting information can be downloaded at: https://
www.mdpi.com/article/10.3390/dj10090162/s1, Table S1: Studies excluded and reasons for exclusion.
Reference [41–57] is cited in the supplementary materials.
Author Contributions: Conceptualization, M.C. (Mario Caggiano) and R.G.; methodology, F.D. and
M.C. (Maria Contaldo); validation, M.P.; investigation, F.D., M.P.D.P. and M.C. (Maria Contaldo); data
curation, M.C. (Mario Caggiano) and R.G.; writing—original draft preparation, F.D. and M.C. (Mario
Caggiano); writing—review and editing, M.P.D.P., R.G., M.C. (Maria Contaldo) and M.P.; supervision,
M.C. (Maria Contaldo). All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Reported data are available on MEDLINE/PubMed, Scopus, Cochrane
library, and BioMed Central databases.
Conflicts of Interest: The authors declare no conflict of interest.
Dent. J. 2022, 10, 162 16 of 18

References
1. Nicolò, M.; Pirozzi, M.; Catalano, C.; Amato, M. Parodontiti associate a malattie sistemiche con deficit qualitativo della funzione
fagocitaria. Nota I. Diabetemellito [Periodontitis associated with systemic diseases with qualitative deficiency of phagocyte
function. I. Diabetes mellitus]. Minerva Stomatol. 1989, 38, 899–903.
2. Nicolò, M.; Bucci, P.; Mignogna, M.D.; Amato, M. Parodontiti associate a malattie sistemiche con deficit qualitativo della funzione
fagocitaria. Nota II. Sindrome di Down [Periodontitis associated with systemic diseases with qualitative deficiency of phagocyte
function. II. Down’s syndrome]. Minerva Stomatol. 1989, 38, 905–909. [PubMed]
3. Nicolò, M.; Amato, M.; Galizia, G.F. Parodontiti associate a malattie sistemiche con deficit qualitativo della funzione fagocitaria.
Nota III. Sindrome di Papillon-Lefèvre [Periodontitis associated with systemic diseases with qualitative deficiency of phagocyte
function. III. Papillon-Lefevre syndrome]. Minerva Stomatol. 1989, 38, 911–915. [PubMed]
4. Di Spirito, F.; Iacono, V.J.; Iandolo, A.; Amato, A.; Sbordone, L. Evidence-based Recommendations on Periodontal Practice and the
Management of Periodontal Patients during and after the COVID-19 Era: Challenging Infectious Diseases Spread by Air-borne
Transmission. Open Dent. J. 2021, 15, 325–336. [CrossRef]
5. Orsini, M.; Orsini, G.; Benlloch, D.; Aranda, J.J.; Sanz, M. Long-term clinical results on the use of bone-replacement grafts in the
treatment of intrabony periodontal defects. Comparison of the use of autogenous bone graft plus calcium sulfate to autogenous
bone graft covered with a bioabsorbable membrane. J. Periodontol. 2008, 79, 1630–1637. [CrossRef] [PubMed]
6. Sbordone, C.; Toti, P.; Brevi, B.; Martuscelli, R.; Sbordone, L.; Di Spirito, F. Computed tomography-aided descriptive analysis of
maxillary and mandibular atrophies. J. Stomatol. Oral Maxillofac. Surg. 2018, 120, 99–105. [CrossRef]
7. Mattioli-Belmonte, M.; Teti, G.; Salvatore, V.; Focaroli, S.; Orciani, M.; Dicarlo, M.; Fini, M.; Orsini, G.; Di Primio, R.; Falconi, M.
Stem cell origin differently affects bone tissue engineering strategies. Front. Physiol. 2015, 6, 266. [CrossRef]
8. Di Spirito, F.; Toti, P.; Brevi, B.; Martuscelli, R.; Sbordone, L.; Sbordone, C. Computed tomography evaluation of jaw atrophies
before and after surgical bone augmentation. Int. J. Clin. Dent. 2019, 12, 259–270.
9. Tonetti, M.S.; Greenwell, H.; Kornman, K.S. Staging and grading of periodontitis: Framework and proposal of a new classification
and case definition. J. Periodontol. 2018, 89, 159–172. [CrossRef]
10. Contaldo, M.; Lucchese, A.; Romano, A.; Della Vella, F.; Di Stasio, D.; Serpico, R.; Petruzzi, M. Oral Microbiota Features in Subjects
with Down Syndrome and Periodontal Diseases: A Systematic Review. Int. J. Mol. Sci. 2021, 22, 9251. [CrossRef]
11. Folliero, V.; Dell’Annunziata, F.; Roscetto, E.; Amato, A.; Gasparro, R.; Zannella, C.; Casolaro, V.; De Filippis, A.; Catania, M.R.;
Franci, G.; et al. Rhein: A novel antibacterial compound against Streptococcus mutans infection. Microbiol. Res. 2022, 261, 127062.
[CrossRef] [PubMed]
12. Contaldo, M.; Lucchese, A.; Lajolo, C.; Rupe, C.; Di Stasio, D.; Romano, A.; Petruzzi, M.; Serpico, R. The Oral Microbiota Changes
in Orthodontic Patients and Effects on Oral Health: An Overview. J. Clin. Med. 2021, 10, 780. [CrossRef] [PubMed]
13. Nastri, L.; Nucci, L.; Carozza, D.; Martina, S.; Serino, I.; Perillo, L.; d’Apuzzo, F.; Grassia, V. Gingival Recessions and Periodontal
Status after Minimum 2-Year-Retention Post-Non-Extraction Orthodontic Treatment. Appl. Sci. 2022, 12, 1641. [CrossRef]
14. Di Spirito, F.; Sbordone, L.; Pilone, V.; D’Ambrosio, F. Obesity and Periodontal Disease: A Narrative Review on Current Evidence
and Putative Molecular Links. Open Dent. J. 2019, 13, 526–536. [CrossRef]
15. Contaldo, M.; Fusco, A.; Stiuso, P.; Lama, S.; Gravina, A.G.; Itro, A.; Federico, A.; Itro, A.; Dipalma, G.; Inchingolo, F.; et al. Oral
Microbiota and Salivary Levels of Oral Pathogens in Gastro-Intestinal Diseases: Current Knowledge and Exploratory Study.
Microorganisms 2021, 9, 1064. [CrossRef] [PubMed]
16. Di Spirito, F.; La Rocca, M.; De Bernardo, M.; Rosa, N.; Sbordone, C.; Sbordone, L. Possible Association of Periodontal Disease
and Macular Degeneration: A Case-Control Study. Dent. J. 2020, 9, 1. [CrossRef] [PubMed]
17. Chapple, I.L.C.; Genco, R. On behalf of working group 2 of the joint EFP/AAP workshop. Diabetes and periodontal diseases:
Consensus report of the Joint EFP/AAPWorkshop on Periodontitis and Systemic Diseases. J. Periodontol. 2013, 84, 106–112.
[CrossRef]
18. Contaldo, M.; Itro, A.; Lajolo, C.; Gioco, G.; Inchingolo, F.; Serpico, R. Overview on Osteoporosis, Periodontitis and Oral Dysbiosis:
The Emerging Role of Oral Microbiota. Appl. Sci. 2020, 10, 6000. [CrossRef]
19. Di Spirito, F.; Toti, P.; Pilone, V.; Carinci, F.; Lauritano, D.; Sbordone, L. The Association between Periodontitis and Human
Colorectal Cancer: Genetic and Pathogenic Linkage. Life 2020, 10, 211. [CrossRef]
20. Papapanou, P.N.; Sanz, M.; Buduneli, N.; Dietrich, T.; Feres, M.; Fine, D.H.; Flemmig, T.F.; Garcia, R.; Giannobile, W.V.; Graziani,
F.; et al. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and
Periimplant Diseases and Conditions. J. Clin. Periodontol. 2018, 45, S173–S182. [CrossRef]
21. Genco, R.J.; Borgnakke, W.S. Risk factors for periodontal disease. Periodontology 2000 2013, 62, 59–94. [CrossRef]
22. D’Ambrosio, F.; Caggiano, M.; Schiavo, L.; Savarese, G.; Carpinelli, L.; Amato, A.; Iandolo, A. Chronic Stress and Depression in
Periodontitis and Periimplantitis: A Narrative Review on Neurobiological, Neurobehavioral and Immune–Microbiome Interplays
and Clinical Management Implications. Dent. J. 2022, 10, 49. [CrossRef]
23. Checchi, V.; Gasparro, R.; Pistilli, R.; Canullo, L.; Felice, P. Clinical Classification of Bone Augmentation Procedure Failures in the
Atrophic Anterior Maxillae: Esthetic Consequences and Treatment Options. BioMed Res. Int. 2019, 2019, 4386709. [CrossRef]
24. Marenzi, G.; Spagnuolo, G.; Sammartino, J.C.; Gasparro, R.; Rebaudi, A.; Salerno, M. Micro-Scale Surface Patterning of Titanium
Dental Implants by Anodization in the Presence of Modifying Salts. Materials 2019, 12, 1753. [CrossRef] [PubMed]
Dent. J. 2022, 10, 162 17 of 18

25. Bruno, V.; Berti, C.; Barausse, C.; Badino, M.; Gasparro, R.; Ippolito, D.R.; Felice, P. Clinical Relevance of Bone Density Values
from CT Related to Dental Implant Stability: A Retrospective Study. BioMed Res. Int. 2018, 2018, 6758245. [CrossRef] [PubMed]
26. Pisano, M.; Amato, A.; Sammartino, P.; Iandolo, A.; Martina, S.; Caggiano, M. Laser Therapy in the Treatment of Periimplantitis:
State-of-the-Art, Literature Review and Meta-Analysis. Appl. Sci. 2021, 11, 5290. [CrossRef]
27. Felice, P.; Bertacci, A.; Bonifazi, L.; Karaban, M.; Canullo, L.; Pistilli, R.; Sammartino, P.; Gasparro, R.; Barausse, C. A Proposed
Protocol for Ordinary and Extraordinary Hygienic Maintenance in Different Implant Prosthetic Scenarios. Appl. Sci. 2021, 11,
2957. [CrossRef]
28. Ramaglia, L.; Di Spirito, F.; Sirignano, M.; La Rocca, M.; Esposito, U.; Sbordone, L. A 5-year longitudinal cohort study on crown to
implant ratio effect on marginal bone level in single implants. Clin. Implant Dent. Relat. Res. 2019, 21, 916–922. [CrossRef]
29. Caggiano, M.; Amato, A.; Acerra, A.; D’Ambrosio, F.; Martina, S. Evaluation of Deviations between Computer-Planned Implant
Position and In Vivo Placement through 3D-Printed Guide: A CBCT Scan Analysis on Implant Inserted in Esthetic Area. Appl.
Sci. 2022, 12, 5461. [CrossRef]
30. Di Spirito, F.; Schiavo, L.; Pilone, V.; Lanza, A.; Sbordone, L.; D’Ambrosio, F. Periodontal and Periimplant Diseases and
Systemically Administered Statins: A Systematic Review. Dent. J. 2021, 9, 100. [CrossRef]
31. Duarte, P.M.; Nogueira, C.; Silva, S.M.; Pannuti, C.M.; Schey, K.C.; Miranda, T.S. Impact of Smoking Cessation on Periodontal
Tissues. Int. Dent. J. 2022, 72, 31–36. [CrossRef] [PubMed]
32. D’Ambrosio, F.; Pisano, M.; Amato, A.; Iandolo, A.; Caggiano, M.; Martina, S. Periodontal and Periimplant Health Status in
Traditional vs. Heat-Not-Burn Tobacco and Electronic Cigarettes Smokers: A Systematic Review. Dent. J. 2022, 10, 103. [CrossRef]
[PubMed]
33. Di Spirito, F.; Pelella, S.; Argentino, S.; Sisalli, L.; Sbordone, L. Oral manifestations and the role of the oral healthcare workers in
COVID-19. Oral Dis. 2022, 28, 1003–1004. [CrossRef]
34. Japuntich, S.J.; Leventhal, A.M.; Piper, M.E.; Bolt, D.M.; Roberts, L.J.; Fiore, M.C.; Baker, T.B. Smoker characteristics and
smoking-cessation milestones. Am. J. Prev. Med. 2011, 40, 286–294. [CrossRef] [PubMed]
35. Di Spirito, F.; Iandolo, A.; Amato, A.; Caggiano, M.; Raimondo, A.; Lembo, S.; Martina, S. Prevalence, Features and Degree of
Association of Oral Lesions in COVID-19: A Systematic Review of Systematic Reviews. Int. J. Environ. Res. Public Health 2022, 19,
7486. [CrossRef]
36. Liberati, A.; Altman, D.G.; Tetzlaff, J.; Mulrow, C.; Gotzsche, P.C.; Ioannidis, J.P.A.; Clarke, M.; Devereaux, P.J.; Kleijnen, J.; Moher,
D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions:
Explanation and elaboration. PLoS Med. 2009, 6, e1000100. [CrossRef]
37. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA
statement. PLoS Med. 2009, 6, e1000097. [CrossRef]
38. Da Costa Santos, C.M.; Pimenta, C.A.M.; Nobre, M.R.C. The PICO strategy for the research question construction and evidence
search. Revis. Lat.-Am. Enferm. 2007, 15, 508–511. [CrossRef]
39. Higgins, J.P.T.; Green, S. (Eds.) Cochrane Handbook for Systematic Reviews of Interventions; John Wiley & Sons, Ltd.: Hoboken, NJ,
USA, 2008.
40. Shea, B.J.; Reeves, B.C.; Wells, G.; Thuku, M.; Hamel, C.; Moran, J.; Henry, D.A. AMSTAR 2: A critical appraisal tool for systematic
reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ 2017, 358, j4008. [CrossRef]
41. Leite, F.; Nascimento, G.G.; Baake, S.; Pedersen, L.D.; Scheutz, F.; López, R. Impact of Smoking Cessation on Periodontitis: A
Systematic Review and Meta-analysis of Prospective Longitudinal Observational and Interventional Studies. Nicotine Tob. Res.
Off. J. Soc. Res. Nicotine Tob. 2019, 21, 1600–1608. [CrossRef]
42. Souto, M.; Rovai, E.S.; Villar, C.C.; Braga, M.M.; Pannuti, C.M. Effect of smoking cessation on tooth loss: A systematic review
with meta-analysis. BMC Oral Health 2019, 19, 245. [CrossRef] [PubMed]
43. Ramseier, C.A.; Woelber, J.P.; Kitzmann, J.; Detzen, L.; Carra, M.C.; Bouchard, P. Impact of risk factor control interventions for
smoking cessation and promotion of healthy lifestyles in patients with periodontitis: A systematic review. J. Clin. Periodontol.
2020, 47 (Suppl. S22), 90–106. [CrossRef] [PubMed]
44. Gugnani, N.; Gugnani, S. Can smoking cessation impact the incidence and progression of periodontitis? Evid.-Based Dent. 2020,
21, 122–123. [CrossRef] [PubMed]
45. Al-Ansari, A. Smoking cessation is effective in reducing the risk of tooth loss. Evid.-Based Dent. 2020, 21, 120–121. [CrossRef]
46. Chambrone, L.; Chambrone, D.; Lima, L.A.; Chambrone, L.A. Predictors of tooth loss during long-term periodontal maintenance:
A systematic review of observational studies. J. Clin. Periodontol. 2010, 37, 675–684. [CrossRef]
47. Chambrone, L.; Preshaw, P.M.; Rosa, E.F.; Heasman, P.A.; Romito, G.A.; Pannuti, C.M.; Tu, Y.K. Effects of smoking cessation
on the outcomes of non-surgical periodontal therapy: A systematic review and individual patient data meta-analysis. J. Clin.
Periodontol. 2013, 40, 607–615. [CrossRef]
48. Fiorini, T.; Musskopf, M.L.; Oppermann, R.V.; Susin, C. Is there a positive effect of smoking cessation on periodontal health? A
systematic review. J. Periodontol. 2014, 85, 83–91. [CrossRef]
49. Holliday, R.; Hong, B.; McColl, E.; Livingstone-Banks, J.; Preshaw, P.M. Interventions for tobacco cessation delivered by dental
professionals. Cochrane Database Syst. Rev. 2021, 2, CD005084. [CrossRef]
50. Alexandridi, F.; Tsantila, S.; Pepelassi, E. Smoking cessation and response to periodontal treatment. Aust. Dent. J. 2018, 63,
140–149. [CrossRef]
Dent. J. 2022, 10, 162 18 of 18

51. Preshaw, P.M.; Heasman, L.; Stacey, F.; Steen, N.; McCracken, G.I.; Heasman, P.A. The effect of quitting smoking on chronic
periodontitis. J. Clin. Periodontol. 2005, 32, 869–879. [CrossRef]
52. Shimazaki, Y.; Saito, T.; Kiyohara, Y.; Kato, I.; Kubo, M.; Iida, M.; Yamashita, Y. The influence of current and former smoking on
gingival bleeding: The Hisayama study. J. Periodontol. 2006, 77, 1430–1435. [CrossRef] [PubMed]
53. Peruzzo, D.C.; Gimenes, J.H.; Taiete, T.; Casarin, R.C.; Feres, M.; Sallum, E.A.; Casati, M.Z.; Kantovitz, K.R.; Nociti, F.H. Impact of
smoking on experimental gingivitis. A clinical, microbiological and immunological prospective study. J. Periodontal Res. 2016, 51,
800–811. [CrossRef] [PubMed]
54. Nemmar, A.; Al-Salam, S.; Beegam, S.; Zaaba, N.E.; Ali, B.H. Effect of smoking cessation on chronic waterpipe smoke inhalation-
induced airway hyperresponsiveness, inflammation, and oxidative stress. Am. J. Physiol. Lung Cell. Mol. Physiol. 2021, 320,
L791–L802. [CrossRef] [PubMed]
55. More, A.B.; Rodrigues, A.; Sadhu, B.J. Effects of smoking on oral health: Awareness among dental patients and their attitude
towards its cessation. Indian J. Dent. Res. Off. Publ. Indian Soc. Dent. Res. 2021, 32, 23–26. [CrossRef]
56. Ravidà, A.; Troiano, G.; Qazi, M.; Saleh, M.; Saleh, I.; Borgnakke, W.S.; Wang, H.L. Dose-dependent effect of smoking and smoking
cessation on periodontitis-related tooth loss during 10–47 years periodontal maintenance-A retrospective study in compliant
cohort. J. Clin. Periodontol. 2020, 47, 1132–1143. [CrossRef]
57. ALHarthi, S.; Natto, Z.S.; Midle, J.B.; Gyurko, R.; O’Neill, R.; Steffensen, B. Association between time since quitting smoking
and periodontitis in former smokers in the National Health and Nutrition Examination Surveys (NHANES) 2009 to 2012. J.
Periodontol. 2019, 90, 16–25. [CrossRef]
58. Karaaslan, F.; Dikilitaş, A.; Yiğit, U. The effects of vaping electronic cigarettes on periodontitis. Aust. Dent. J. 2020, 65, 143–149.
[CrossRef]
59. Jeong, W.; Choi, D.W.; Kim, Y.K.; Lee, H.J.; Lee, S.A.; Park, E.C.; Jang, S.I. Associations of electronic and conventional cigarette use
with periodontal disease in South Korean adults. J. Periodontol. 2020, 91, 55–64. [CrossRef]
60. Costa, F.O.; Cota, L.O.; Lages, E.J.; Cyrino, R.M.; Oliveira, A.M.; Oliveira, P.A.; Cortelli, J.R. Associations of duration of smoking
cessation and cumulative smoking exposure with periodontitis. J. Oral Sci. 2013, 55, 245–253. [CrossRef]
61. Costa, F.O.; Cota, L. Cumulative smoking exposure and cessation associated with the recurrence of periodontitis in periodontal
maintenance therapy: A 6-year follow-up. J. Periodontol. 2019, 90, 856–865. [CrossRef]
62. Dietrich, T.; Walter, C.; Oluwagbemigun, K.; Bergmann, M.; Pischon, T.; Pischon, N.; Boeing, H. Smoking, Smoking Cessation,
and Risk of Tooth Loss: The EPIC-Potsdam Study. J. Dent. Res. 2015, 94, 1369–1375. [CrossRef] [PubMed]
63. Liu, K.H.; Hwang, S.J. Effect of smoking cessation for 1 year on periodontal biomarkers in gingival crevicular fluid. J. Periodontal
Res. 2016, 51, 366–375. [CrossRef] [PubMed]
64. Beklen, A.; Yildirim, B.G.; Mimaroglu, M.; Yavuz, M.B. The impact of smoking on oral health and patient assessment of tobacco
cessation support from Turkish dentists. Tob. Induc. Dis. 2021, 19, 49. [CrossRef]
65. Valente, N.A.; Andreana, S. Peri-implant disease: What we know and what we need to know. J. Periodontal Implant Sci. 2016, 46,
136–151. [CrossRef] [PubMed]
66. Helal, O.; Gostemeyer, G.; Krois, J.; Fawzy, E.S.; Sayed, K.; Graetz, C.; Schwendicke, F. Predictors for tooth loss in periodontitis
patients: Systematic review and meta-analysis. J. Clin. Periodontol. 2019, 46, 699–712. [CrossRef]
67. Koldsland, O.C.; Scheie, A.A.; Aass, A.M. The association between selected risk indicators and severity of peri-implantitis using
mixed model analyses. J. Clin. Periodontol. 2011, 38, 285–292. [CrossRef]
68. Di Spirito, F. Oral-Systemic Health and Disorders: Latest Prospects on Oral Antisepsis. Appl. Sci. 2022, 12, 8185. [CrossRef]
69. Roos-Jansåker, A.M.; Renvert, H.; Lindahl, C.; Renvert, S. Nine- to fourteen-year follow-up of implant treatment. Part III: Factors
associated with peri-implant lesions. J. Clin. Periodontol. 2006, 33, 296–301. [CrossRef]
70. Bergström, J. Tobacco smoking and chronic destructive periodontal disease. Odontology 2004, 92, 1–8. [CrossRef]
71. Dietrich, T.; Bernimoulin, J.P.; Glynn, R.J. The effect of cigarette smoking on gingival bleeding. J. Periodontol. 2004, 75, 16–22.
[CrossRef]
72. Bašić, K.; Peroš, K.; Bošnjak, Z.; Šutej, I. Subgingival Microbiota Profile in Association with Cigarette Smoking in Young Adults: A
Cross-Sectional Study. Dent. J. 2021, 9, 150. [CrossRef] [PubMed]
73. Nociti, F.H.; Casati, M.Z.; Duarte, P.M. Current perspective of the impact of smoking on the progression and treatment of
periodontitis. Periodontology 2000 2015, 67, 187–210. [CrossRef] [PubMed]
74. Jha, P.; Peto, R. Global effects of smoking, of quitting, and of taxing tobacco. N. Engl. J. Med. 2014, 370, 60–68. [CrossRef]
75. Chaffee, B.W.; Couch, E.T.; Vora, M.V.; Holliday, R.S. Oral and periodontal implications of tobacco and nicotine products.
Periodontology 2000 2021, 87, 241–253. [CrossRef] [PubMed]
76. Dhillon, A.Z.; Doran, T.; Aggarwal, V.R. Perceptions of Waterpipe Smoking among Young Adults: A Phenomenological Study.
Dent. J. 2020, 8, 134. [CrossRef] [PubMed]
77. Julkunen-Iivari, A.; Heikkinen, A.M.; Räisänen, I.T.; Ruokonen, H.; Meurman, J.H.; Toppila-Salmi, S.; Söder, P.-Ö.; Söder, B.
Tobacco Products, Periodontal Health and Education Level: Cohort Study from Sweden. Dent. J. 2020, 8, 90. [CrossRef]
78. Di Spirito, F.; Amato, A.; Di Palo, M.P.; Contaldo, M.; D’Ambrosio, F.; Lo Giudice, R.; Amato, M. Oral Lesions Following
Anti-SARS-CoV-2 Vaccination: A Systematic Review. Int. J. Environ. Res. Public Health 2022, 19, 10228. [CrossRef]
79. D’Ambrosio, F.; Di Spirito, F.; De Caro, F.; Lanza, A.; Passarella, D.; Sbordone, L. Adherence to Antibiotic Prescription of Dental
Patients: The Other Side of the Antimicrobial Resistance. Healthcare 2022, 10, 1636. [CrossRef]
80. Amato, A. Oral-Systemic Health and Disorders: Latest Advances on Oral–Gut–Lung Microbiome Axis. Appl. Sci. 2022, 12, 8213.
[CrossRef]