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  <title>Article_6_4_3-Obradovic</title>
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  <content>ORAL MEDICINE
SMOKING AND RECURRENT APHTHOUS STOMATITIS




                                                                                                                                                                               Original Articles
Radmila Radisa Obradović1a*             , Marija LJ Igic2a, Aleksandar D Mitic3a           , Ana S Pejcic1a   , Kosta M Todorovic4b                         ,
Zana Popovic5c

1
 Department of Periodontology and Oral Medicine, Faculty of Medicine, Niš University, Serbia
2
 Department of Children and Preventive Dentistry, Faculty of Medicine, Niš University, Serbia
3
 Department of Dental Pathology and Endodontics, Faculty of Medicine, Niš University, Serbia
4
 Department of Oral Surgery, Faculty of Medicine, Niš University, Serbia
5
 Department of Dentistry, Faculty of Medical Sciences, Kragujevac University, Serbia

a
  DDS, PhD, Professor
b
  DDS, Assistant
c
 DDS, Postdoctoral Student

ABSTRACT                      DOI: https://doi.org/10.25241/stomaeduj.2019.6(4).art.3                                  OPEN ACCESS This is an Open Access
                                                                                                                       article under the CC BY-NC 4.0 license.
Introduction: Recurrent aphthous stomatitis (RAS) is one of the most usual
inflammatory diseases of the oral mucosa. The clinical characteristics of RAS are                                      Peer-Reviewed Article

well defined, but the exact etiology and pathogenesis of the disease are not.                                      Citation: Obradović RR, Igic M, Mitic A, Pejcic A,
                                                                                                                   Todorovic K, Popovic Z. Smoking and recurrent
Several investigations have noticed cigarette smoking to have a protective effect                                  aphthous stomatitis. Stoma Edu J. 2019;6(4):237-240
on RAS. The aim of the study is to investigate the association between cigarette                                   Received: July 08, 2019
smoking and RAS in order to improve the current knowledge on this issue.                                           Revised: October 25, 2019
                                                                                                                   Accepted: October 28, 2019
Methodology: 68 patients with RAS participated in the study. A full mouth                                          Published: December 16, 2019
clinical examination was performed and an anamnesis was taken for each patient.                                    *Corresponding author:
The statistical analysis was performed using Student t-test.                                                       Professor Radmila Radisa Obradović, DDS, PhD
                                                                                                                   Department of Periodontology and Oral Medicine,
Results: While 6 (8.9%) of patients with RAS were smokers, a significantly higher                                  Faculty of Medicine, Niš University 81, Dr Zoran Djindjic
percentage (24.9%) among the subjects with RAS were not smokers (group II) (χ2                                     Blvd, 18000 Niš, Serbia
                                                                                                                   Tel: +381-64-235-9595,
=70.4; d.f. = 2, P &lt; 0.001).                                                                                       Fax: +381-18-42-38-770,
                                                                                                                   e-mail: dr.rada@yahoo.com
Conclusion: The negative association between smoking and RAS indicated by
                                                                                                                   Copyright: © 2019
this investigation is not meant to encourage people to smoke nor to spare them                                     the Editorial Council for the Stomatology Edu Journal.
from the intention to quit their habit. These conclusions should be used to clear
up the cause and pathogenesis of the RAS and to identify better prevention and
treatment.
Keywords: Oral medicine; Aphthae; Mouth; Smoking; Oral health,
Recurrent Aphthous Stomatitis, Smoking.


1. Introduction                                                                are produced [3]. Inheritance of HLA-B51 antigen,
Recurrent aphthous stomatitis (RAS) is a very common                           vitamin B12 deficiency, recurrent herpes labialis,
disease of the oral mucosa. It is called minor aphthous                        Helicobacter pylori, hepatitis C and hypersensitivity
ulcers, herpetiform ulcers, aphthosis and many other                           to nickel are involved in the development of
names. Aphthous ulcers can occur alone or as part of                           RAS [4,5]. It is necessary to better understand
a syndrome [1]. RAS occurs only in non-keratinized                             the pathogenesis and primary cause of RAS [2].
mucosa as painful, shallow round ulcers with an                                Previously, it is thought that approximately 0.89%
erythematous halo covered by a membranous layer.                               of the adults over 17 years of age have at least one
The clinical ulcerative period for minor aphthous                              aphthous lesion and that males (1.13%) have almost
ulcers may last for 2 weeks and lesions usually heal                           twice the RAS than females (0.67%). It is noticed
without a scar [2]. The clinical characteristics of RAS                        that reported prevalence of RAS varies according
are well known, but the exact etiology and patho-                              to patient selection, presence of lesions at the time
genesis of the disease are not complete. The etiology                          of investigation or during a specified period and
of RAS includes stress, microorganisms, food hyper-                            newer literature data show that the RAS prevalence
sensitivity, immune dysregulation, hormonal fac-                               is between 5 and 60%, depending on the population
tors and a genetic predisposition, usage of the                                group studied [2].
toothpaste with SLS [1,2]. Current investigations                              It is estimated that tobacco use is the major cause of
have focused on a possible immunopathogenesis of                               more than 5 million deaths every year [6]. Smoking
RAS [2,3]. The epithelial cell death and the creation                          is a common risk factor in a number of chronic
of ulceration probably results from the activation of                          diseases like lung diseases, cancer, cardiovascular
a cell-mediated immune response in which Tumor                                 diseases; and a major risk factor in the prevalence of
Necrosis Factor Alpha (TNFα) and other cytokines                               periodontal diseases [6-10]. Cigarette smoke contains



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                    SMOKING AND RECURRENT APHTHOUS STOMATITIS



                    Table 1. Relationship between RAS and smoking.
Original Articles
                                                               RAS                   (no RAS or RAS history)               Total
                        Smoking          (group I)           6 (8.9%)                       68 (91.9%)                         74
                        Nonsmoking (group II)               62 (24.9%)                      202 (76.5%)                    264

                                 Total                      68 (20.1%)                      270 (79.9%)                    338


                    approximately 4800 chemicals, with over 60 of them         patients constituted group II (264 patients).
                    known to have 3 damaging effects on human cells
                    [11]. Cigarette smoking could camouflage signs of          4. Results
                    periodontal disease like gingival bleeding or redness,     There were 68 participants with RAS, out of which 31
                    by suppressing the immune response which could             (46.92%) were men and 37 (53.1%) were women. The
                    cause a problem in the diagnosis of the disease.           average age was 29.7± 8.8 years. 66 (97.1%) had the
                    Several studies have noticed cigarette smoking to          minor type of the disease, 2 (2.9%) had both minor
                    have a protective effect on RAS [12-15]. It is not clear   and major RAS.
                    how cigarette smoking can reduce RAS prevalence            The relationship between RAS and smoking is
                    but it is thought that immunological mechanisms            shown in Table 1. While 6 (8.9%) of patients with RAS
                    are involved and that the cytokine (TNF) plays an          were active smokers (group I), a significantly higher
                    important role in the pathogenesis. Nicotine has           percentage (24.9%) among the subjects with RAS
                    been shown to influence the immune response in             were not smokers (group II) (χ2 =70.4; d. f. = 2, P &lt;
                    inflammatory conditions [16,17]. It acts through the       0.001).
                    central nervous system inducing the production
                    of glucocorticoids and activating the autonomic            5. Discussion
                    nervous system and consequently reducing the level         Smoking is a known risk factor in a number of chronic
                    of inflammation [16].                                      diseases and major risk factor of periodontal disease
                    Nicotine can activate the nicotinic acetylcholine          [2-6]. Cigarette smoking suppresses the immune
                    receptors on macrophages and reduce the                    host response, masks early signs of periodontal
                    production of TNF1and interleukins [17].                   disease and has as reported by some authors a
                                                                               beneficial protective effect on RAS. It has also been
                    2. The aim of the study                                    noticed that the incidence of RAS is higher among
                    The aim of the study is to investigate the association     young individuals and that adults younger than 40
                    between cigarette smoking and RAS in order to              years of age have more than twice higher RAS rate
                    increase current knowledge on this issue.                  than those older than 40 years [12-15]. We noticed
                                                                               similar results in our study where the average age
                    3. Methodology                                             of the patients with RAS was 29.7±8.8 years. It
                    The study was conducted on 338 patients who                could be suspected that stress could be an aphthae
                    came at the Department of Oral Medicine and                provoking factor. Previously, lifestyle could induce
                    Periodontology of the Dental Clinic of Faculty of          stress and social conditions and self-management
                    Medicine, Niš University, for one year. The Ethics         are important determinants of health. The effects
                    Committee of the Faculty of Medicine Niš approved          of living exposed to many stress factors may cause
                    the study protocol (evidential number 01-2800-7).          poorer health and more frequent occurrence of RAS
                    After the medical history was taken, the patients          [18,19]. Literature data reveal a significant reduction
                    who had undergone antibiotic and corticosteroid            of RAS in individuals who smoke. The prevalence
                    therapy in the last three months, were not included        and odds ratios for number of cigarettes smoked is
                    in the study. A full mouth clinical examination was        significant and suggest a dose response effect [14,15].
                    performed and the patients with active aphthous            A reduction in RAS prevalence with higher blood
                    lesions and who per medical history had suffered           levels of nicotine is found to be significant [20].
                    from oral ulcers at least once within a period of 5        Our study noticed a similar situation. where 8.9%
                    months were considered to suffer from RAS. The             of patients with RAS were active smokers and a
                    patients with other oral diseases who came at the          significantly higher percentage (24.9%) among
                    Dental Clinic of the Medical Faculty Niš for other         the subjects with RAS were not smokers (group II)
                    medical reasons were also included in this study.          (χ2 =70.4; d. f. = 2, P &lt; 0.001). Kalpana [13] noticed
                    Out of all the examined patients, 68 patients had          that significant differences exist in the prevalence
                    RAS and 270 had no RAS or RAS history. Patients            of RAS among cigarette smokers, which could be
                    who smoked over 10 cigarettes per day (per medical         related to the number of cigarettes smoked per day
                    history) were considered to be “smokers” and they          and duration of the habit. The “protective effect” on
                    constituted group I (74 patients). The nonsmoking          RAS was noticed only when the persons were heavy



 238                                                         Stoma Edu J. 2019;6(4): 237-240                   www.stomaeduj.com
                                                                            SMOKING AND RECURRENT APHTHOUS STOMATITIS



smokers or had smoked for longer periods of time.                        by a bias of selection of the sample. Other researchers




                                                                                                                                                Original Articles
Cigarette non-smokers have far greater odds of RAS                       have found a lower incidence of RAS in smokers on
than individuals who smoked &gt;1 pack per day. It                          the basis of the disease history but not by direct
could was concluded that the associations of RAS                         detection of present lesions by a practitioner [12-14].
with cigarette smoking and with cotinine levels                          A similar negative correlation between smoking and
were significant. Our study noticed similar results,                     RAS was noticed in our study. The treatment and,
namely that a higher number of individuals with                          many times, the diagnosis of RAS are a challenge
RAS were nonsmokers (24.9%). RAS is characterized                        in the daily life of the clinician. Dental professionals
by recurrences of short-lived lesions. The lesions                       and otorhinolaryngologists are usually responsible
are not always noticed at the time of examination                        for the first contact with the patients who have RAS.
and the diagnosis is often based on the patient’s                        These professionals should be alert to the clinical
clinical history. The statistical evaluation of RAS is                   aspects of this condition since each patient will
hampered because lesions cannot be evaluated by                          be treated in an individualized manner, because
the investigator at any time and is usually based on                     treatment is usually palliative and not curative.
a self-reported history of RAS. Such a diagnosis is
less reliable that one based upon the observation of                     6. Conclusion
present lesions by a practitioner. It is to be noticed                   On the basis of the aim of the study, its applied
that many of the studies which found a negative                          methodology and the results obtained it can be
correlation between RAS and smoking were based                           concluded that the incidence of RAS is higher
on a self-reported history of RAS [21]. Information                      among young individuals and among subjects who
should be carefully interpreted, especially where                        do not smoke. The negative association between
there is some basis to suspect response bias. The                        smoking and RAS in our study is not indeed meant to
findings in this study were based on anamnesis                           encourage people to smoke nor to sway them in the
and clinical examination conducted by an                                 decision to quit their habit. Smoking cessation is the
experienced practitioner and provide data on the                         main option to remove the harmful tobacco effects
general prevalence of RAS in smokers. There is a                         on oral tissues and to improve the quality of life.
small number of studies in which patients were
diagnosed by direct detection of present lesions                         Author Contributions
by a practitioner. Queiroz et al [22] evaluated 4895                     All authors (RO, MI, AM, AP, KT, and ZP) contributed in
cases of recurrent aphthous ulcerations with a focus                     data collection and analysis, and manuscript writing.
on treatment, diagnosis and etiology. Data such                          All authors agree to be accountable for the content
as sex, age, race, location, smoking habits, types                       of the work.
of treatment, relapsing episodes, laboratory test
results and clinical characteristics were collected.                     Acknowledgment
Regarding smoking habits, in the majority of                             This research was supported by a grant from the
patients, 59 (77.6%) smoking was not recorded. The                       Internal project number 11, Medical Faculty,
investigators did not consider the percentages of                        University of Niš, Niš, Serbia.
smoking notifications because they are influenced




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                                                                                                            Radmila Radisa OBRADOVIĆ
                                                                                                              DDS, PhD, Professor
                                                                                  Department of Oral Medicine and Periodontology
                                                                                                                     Dental Clinic
                                                                                                              Faculty of Medicine
                                                                                                                    Niš University
                                                                                                                       Niš, Serbia


                    CV
                    Doctor Radmila Radisa Obradović is a Professor at the Department of Oral Medicine and Periodontology, Dental Clinic,
                    Faculty of Medicine, Niš University and at the Department of Oral Medicine and Periodontology, Faculty of Medical
                    Sciences, Kragujevac, Serbia. She is also a member of the Niš Dental Clinic’s Ethical Committee, Serbian Medical Society,
                    Serbian Anthropological Society and Serbian Oral Laser Society (SOLAS).
                    She participates in national projects, and delivers many dental courses and conferences as a lecturer.
                    She has many scientific publications in international and Serbian medical and dental journals.


                    Questions
                    1. Recurrent aphthous stomatitis (RAS) is very common disease of the oral mucosa. It is
                    called:
                    qa. Minor aphthous ulcers;
                    qb. Herpetiform ulcers;
                    qc. Simple aphthosis;
                    qd. All of the above answers are correct

                    2. Cigarette smoking could influence signs of periodontal disease like:
                    qa. Provoking bleeding;
                    qb. Provoking gingival redness;
                    qc. Camouflage gingival bleeding or redness;
                    qd. Provoking gingival swelling.

                    3. The etiology of RAS includes:
                    qa. Stress and immune dysregulation;
                    qb. Microorganisms and food hypersensitivity;
                    qc. Hormonal factors and a genetic predisposition;
                    qd. All of the above answers are correct.

                    4. The patients were divided into:
                    qa. Two groups: smokers and nonsmoking patients;
                    qb. Three groups: smokers, nonsmoking patients and patients with RAS;
                    qc. Two groups: smokers and patients with RAS;
                    qd. Two groups: nonsmoking patients and patients with RAS.




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