Introduction

Periodontal maintenance therapy (PMT) can be considered a critical factor for success in controlling periodontitis and in the long-term maintenance of teeth ¹. In addition, neglecting a regular PMT program has been associated with increased risk of reinfection and progression of periodontitis, as well as increased tooth loss (TL) ^2,3.

During periodontal clinical reevaluation in PMT, it is important to analyze the biological, behavioral, and social risk variables associated with periodontal disease, especially smoking, dental plaque scores, and diabetes mellitus ^4,5,6. Moreover, many other factors can affect clinical outcomes during PMT: degree of compliance and adherence to the proposed recommendations, oral hygiene practice, age, smoking status, systemic diseases that can compromise the immune response, initial tooth prognosis, tooth location, residual periodontal pockets, and bleeding on probing (BOP). These factors have been cited as critical for periodontal condition stability ^7,8.

Identification of risk variables for TL in PMT programs can help clinicians and periodontists establish the frequency of recall visits, as well as improve the adherence to maintenance programs, with greater compliance from individuals ⁹. Several studies have demonstrated the effectiveness of periodontal therapy in reducing TL rates, as well as the importance of PMT compliance ^10,11,12,13.

Smoking is an important risk factor for periodontitis. Various studies have shown that this deleterious habit is strongly associated with increased susceptibility to periodontitis, increased periodontitis severity and progression, as well as higher TL ^14,15,16,17.

Although TL has already been reported by longitudinal studies among individuals undergoing PMT ^{1,7,8,18,19,20,21,22,23,24,25,26}, the independent effect of smoking on TL, adjusted for important confounding variables (i.e. age, gender, diabetes, and socioeconomic level) in individuals undergoing PMT, has not yet been evaluated through systematic review and meta-analysis. Therefore, this paper aimed to evaluate scientific evidence of the independent effect of smoking on TL among individuals undergoing PMT.

Material and methods

This systematic review was registered in PROSPERO (n. CRD42016026083) and was conducted in agreement with the guidelines of Transparent Reporting of Systematic Reviews and Meta-Analyses (PRISMA Statement) ²⁷.

Focal question

Our clinical question (PICO) was: “what is the effect of smoking on tooth loss, for individuals undergoing periodontal maintenance therapy?” (P = individuals undergoing PMT; I = smoking; C = nonsmoker individuals undergoing PMT; O = tooth loss).

Inclusion criteria

Epidemiological clinical studies (observational studies and clinical trials), containing data on TL among smokers and nonsmokers undergoing PMT, were included. There was no restriction regarding age, language, date of publication or follow-up period.

Exclusion criteria

Papers with absence of nonsmokers (control group), case reports or case series, letters to the editor, and literature reviews were excluded.

Search strategy

The databases included MEDLINE via PubMed (https://pubmed.gov), Web of Science (https://isiknowledge.com), Cochrane Library (https://cochrane.org/index.htm), and Scopus (https://scopus.com).

No restrictions were imposed with regard to language or year of publication. MeSH terms, keywords, and other selected terms were searched. Boolean operators (OR, AND) were used to combine searches. The following search strategy was used in MEDLINE, Web of Science, Cochrane and Scopus: ((periodontal disease [Mesh] OR periodontitis [Mesh] OR periodontitis OR maintenance periodontal therapy OR periodontal maintenance OR supportive periodontal therapy OR maintenance care OR long-term care [Mesh] OR long-term maintenance) AND (smoke [Mesh] OR smoke OR smoker* OR tobacco OR tobacco smoker*) AND (tooth loss [Mesh] OR tooth loss OR tooth mortality OR dental mortality)).

A manual and grey literature search was performed through the ISRCTN Registry (http://isrctn.com) and Clinical Trials (https://clinicaltrials.gov) databases. Manual searches in the reference lists of included articles were also performed. The reference list retrieved by the electronic databases search was organized by EndNote software, version 17.0 (https://www.endnote.com).

Initially, 780 articles were found. After the removal of 138 duplicates, 642 articles were available for selection. The selection of articles was based on abstracts and titles and carried out independently by three trained and calibrated researchers (A.M.O.A., R.M.C., and T.R.V.). An initial reading of a 10% sample of the list was performed and the kappa agreement was of 0.84. Thus, the three researchers continued reading the remaining articles. Disagreements were resolved by discussion and consensus. After this phase, 44 studies were selected for full text analysis. This analysis was performed independently by each of the three researchers and disagreements were again resolved by discussion and consensus Figure 1. When a study had missing data or additional information was needed, the corresponding author was contacted.

Figure 1 Flowchart: search strategy and screening process.

Data extraction and methodological quality assessment

Data extraction followed a form in which the following information was extracted: study design, sample size, interval time, dental care protocols and procedures, smoking status, and number and/or mean of teeth lost during PMT Tables 1 and 2, for cohort studies and case-control studies, respectively).

Table 1 Cohort studies characteristics.

Table 2 Case-control studies characteristics.

The methodological quality of the included studies was assessed via the Newcastle-Ottawa Scale (NOS), by two independent reviewers (A.M.O.A. and T.R.V.). Case-control and cohort studies were evaluated by the NOS for case-control studies and the NOS for cohort studies, respectively. Criteria was comprised of three main items: sample selection, comparability, and exposure Tables 3 and 4.

Selection: whether the study had data on smoking status during PMT, to determine cases and/or exposed individuals.

Table 3 Quality assessment of included cohort studies based on the Newcastle-Ottawa Scale.

Table 4 Quality assessment of included case-control studies based on the Newcastle-Ottawa Scale.

Comparability: whether smoking was adjusted for two or more factors, e.g. diabetes, age, gender, or other risk variables. In this case, a maximum of two points could be assigned (one for each confounder).

Outcome of interest or Exposure: whether TL was clinically assessed using clinical examination, radiographic examination, through existing recorded data, or through self-report.

For case-control studies, the NOS scale ranges from 0 (lower methodological quality) to 9 (higher methodological quality). For cohort studies, it ranges from 0 to 10.

Meta-analysis

Comprehensive Meta-Analysis Software, version 2 (https://www.meta-analysis.com/), was used for meta-analysis. Odds ratio (OR) and 95% confidence interval (95%CI) for TL in smokers and nonsmokers were extracted as reported in the studies. I² heterogeneity and sensitivity tests were performed ²⁸. For medium to moderate heterogeneity and for low heterogeneity (< 25%), the random effect (≥ 25%) and the fixed effect were used, respectively. Funnel plot analysis was not performed due to the absence of sufficient study numbers ²⁹. Instead, publication bias was analyzed qualitatively.

Quality of evidence

Two reviewers (C.C.M. and F.O.C.) evaluated evidence quality using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) ³⁰. Disagreements were resolved by discussion and consensus. GRADE evaluates evidence quality as high, moderate, low, or very low. Evidence quality assessment was performed through the GRADE PRO software (https://www.gradepro.org) Box 1.

Box 1 Quality of evidence evaluated through GRADE (Grading of Recommendations, Assessment, Development and Evaluation).

Results

Selection of studies

Eleven papers were included in this systematic review Figure 1: seven cohort studies ^{5,9,20,23,24,31,32}, and four case-control studies ^3,33,34,35. The final selection included no controlled clinical trials.

Quality assessment

Results of the quality assessment are summarized in Tables 3 and 4, for case-control and cohort studies, respectively. Studies were evaluated using the NOS, with scores varying from 7 to 9 for cohort studies, and 7 to 8 for case-control studies. Among cohort studies, one did not specify TL rate of the sample ²⁰, while four studies adjusted smoking only for one confounding factor ^{20,23,24,31,32}. Among case-control studies, TL rate of samples was not specified ^34,35, and only one confounding factor was adjusted ^3,33,34,35.

Studies description

Overall, follow-up time of individuals undergoing PMT ranged from 1 ³⁴ to 36 years ²³. The study sample included a minimum of 288 and a maximum of 6,431 individuals ³⁴. Three studies were case-control studies nested in cohort studies, including 238 individuals ^3,33,35. Some studies ^3,33 evaluated the number of teeth lost and TL percentage in comparisons between regular complier (RC) and irregular complier (IC) individuals. One study ³⁵ evaluated the number of teeth lost and TL percentage in individuals with diabetes and good glycemic control compared to individuals with diabetes and poor glycemic control, and to individuals without diabetes.

The 11 selected studies recruited and treated individuals at different clinics. Participants of five studies were treated in private clinics ^3,9,23,33,35 and participants of six studies were treated in university clinics ^{5,20,24,31,32,34}. One study had a mixed sample, with individuals from private and university clinics ³⁴.

Recall visits during PMT were performed with different time intervals, taking into consideration individuals' degree of compliance: 3 months ^5,33,34, 4 months ³, 4-6 months ³⁵, 6 months ⁹, 3-12 months ³¹, 12 months ^20,24,32, and 18 months ⁹.

Besides their different recall time intervals, studies also diverged in relation to dental care protocols and procedures performed during PMT. In one study ²⁰, dental prophylaxis and subgingival debridement were performed when the operator deemed necessary, and periodontal conditions were documented annually with probing depth (PD) and plaque index (PI) values. In another study ²⁴, all subjects were instructed to perform their own PMT. At each initial return visit, they underwent a questionnaire by a trained interviewer, to record reasons for TL. In other studies ^23,32, all subjects underwent the following PMT protocol: oral hygiene instructions, scaling and root planning, crown polishing, and surgical periodontal therapy (when indicated). Studies evaluated different periodontal parameters: BOP, PI, PD, and clinical attachment level (CAL) ⁵, as well as PI, PD, BOP, and bone level radiographic measurements Table 1. During the monitoring visits, complete periodontal clinical examinations, nonsurgical and surgical procedures were also performed ^3,34 Table 2.

Smoking status characterization

Different definition criteria for smoking status were adopted. Some studies ^33,34,35 classified smokers and former smokers (individuals who reported having smoked more than 100 cigarettes during their lifetime) and nonsmokers according to the criteria by Tomar & Asma ³⁶. Other studies ^3,9,32 classified nonsmokers and former smokers (individuals who smoked 10-19 cigarettes per day) and smokers (individuals who smoked more than 19 cigarettes per day) according to a previous study ³⁷. In a study by Ravald & Johansson ³¹, subjects were divided into three categories: smokers who consume 1-9 cigarettes per day, smokers who consume more than 10 cigarettes per day, and nonsmokers. In a study by Leung et al. ²⁴, 11.3% of the individuals were classified as current smokers, with self-reported consumption of 0.5-56.9 packets/year. In a study by Chambrone & Chambrone ²³, individuals were classified as smokers or nonsmokers, but the number of cigarettes smoked per day was not reported. In a study by Fisher et al. ⁵, smoking status was determined by self-report, while an analysis of expired carbon monoxide concentration identified and quantified the smoking status. A concentration of ≤ 8ppm (parts per million) defined nonsmokers, and a concentration of > 8ppm defined smokers, according to the criteria by Scott et al. ³⁸. A study by König et al. ²⁰ classified smokers and nonsmokers but did not describe smoking status.

Summarization of findings

Ten out of 11 selected studies in this systematic review concluded that smoking was an important factor, significantly associated with TL. Smokers had a greater chance of TL in comparison to nonsmokers [(crude OR = 8.0; 95%CI: 1.6-39.0) ³¹; (adjusted OR = 4.76; 95%CI: 1.42-15.89) ²³; (adjusted OR = 4.1; 95%CI: 1.98-11.6) ³⁵; (adjusted OR = 3.41; 95%CI: 1.26-11.41) ³].

TL occurrence due to periodontal reasons was 2.5 times higher in smokers than in nonsmokers ²⁴. According to one study ²⁰, smoking was significantly associated with TL (r² = 0.12). The same association was also observed among individuals in a private clinic, where smoking was significantly associated with TL (adjusted OR = 3.1; 95%CI: 1.98-11.6) ³⁴.

Smokers among IC individuals (OR = 7.3; 95%CI: 1.17-14.9) presented a greater chance of TL when compared to smokers among RC individuals (OR = 4.2; 95%CI: 1.42-9.89) ³². In another study from the same research group ⁹, IC smokers lost significantly more teeth (adjusted OR = 4.22; 95%CI: 2.01-8.78).

Only one study did not find a statistically significant difference in the mean number of teeth lost between smokers and nonsmokers (at baseline and after three years of PMT) (p > 0.05) ⁵.

Four studies were included in the meta-analysis ^9,23,31,32 Figure 2. There was a statistically significant association of TL and smoking habits (OR = 3.24; 95%CI: 1.33-7.90). The quality of evidence was determined to be moderate for smokers undergoing PMT and for odds of TL (Box 1).

Figure 2 Meta-analysis.

Discussion

In this systematic review and meta-analysis, smokers undergoing PMT presented a greater chance of TL when compared to nonsmokers in 10 out of 11 selected studies, and also in the meta-analysis. However, several factors seem to have impacted these findings.

Although the meta-analysis presented a relative statistical homogeneity, it was limited due to the inclusion of only four studies. Seven studies were excluded from the meta-analysis due to insufficient data for extraction.

Other limitations can also be pointed out, such as clinical and methodological heterogeneity among included studies. The quality of the evidence was determined to be moderate, since there was “serious” imprecision due to the wide confidence interval. Moreover, publication bias was observed ³⁹. These issues can limit the validation of the findings, indicating the need for additional, more robustly designed studies, including a greater number of individuals.

There were differences in time intervals for recall visits during PMT, varying from 3 ^5,33,34 to 18 months ⁹. In addition to the differences in reevaluation intervals, the studies also diverged in relation to maintenance protocols and periodontal procedures performed during PMT, including the evaluation of different clinical parameters. Additionally, different criteria to establish regular or irregular PMT compliance may have had a high impact on studies' different periodontal and TL outcomes.

Regarding smoking status characterization, different criteria were considered. In some studies ^{3,9,23,24,32,35}, individuals were grouped into smokers or nonsmokers according to self-report. Analysis of expired carbon monoxide concentration was also employed ⁵. One study ²⁰ classified smokers and nonsmokers but did not describe its criteria for definition of smoking status. It should be noted that, even though there is a relative agreement on TL rates reported in these studies, there is also a lack of information on methodological issues, which can lead to difficulty in establishing comparisons between studies.

When evaluating study quality, the follow-up interval then adopted was considered sufficient to deal with the occurrence of TL, since eligible studies showed a great variation in the follow-up period: from a minimum of 1 year ³⁴ to a maximum of 36 years ²³. The mean time required for the occurrence of TL is subjected to many factors and is difficult to establish from the literature. A minimum follow-up interval of 12 months was considered adequate, and all studies fulfilled this quality requirement. However, clinical responses to periodontal treatment over time are unpredictable, involving many variables, such as periodontal diseases (and its related prognostic factors, e.g. severity of periodontal disease, degree of compliance during APT and PMT), endodontic pathologies, extensive caries lesions, gender, age, individual tooth prognosis, global prognosis, systemic conditions (e.g. diabetes, smoking), socioeconomic conditions, clinical training and operator experience, quality of dental care, and “philosophical” differences in the treatment ⁹ (particularly issues related to the maintenance or extraction of periodontally compromised teeth and replacement by dental implants) ^40,41.

One systematic review ⁸ included 13 retrospective cohort studies that evaluated prognostic risk factors in individuals undergoing PMT. Results showed that only 6.8% of all teeth were extracted for periodontal reasons, allowing us to speculate that teeth can be preserved for as long as possible. However, other than extraction due to periodontal reasons, other reasons were also considered, such as endodontic complications, root fractures, caries lesions, prosthetic reasons (i.e. loss of crown retention), unknown reasons, or due to differences in treatment philosophies.

Another systematic review analyzed the effect of individuals' PMT compliance on TL and investigated the potential factors affecting the association between compliance and TL. The final analysis included eight studies: seven retrospective cohort studies and one prospective cohort study ⁹. In the retrospective studies, it was difficult to determine clear reasons for tooth extraction, so the differentiation of the reasons underlying extractions are usually divided only into periodontal and other reasons. This fact was observed in this systematic review, as well as in the retrospective studies ^11,20.

Certain studies ^1,8 suggest a lower risk of TL in individuals with greater PMT compliance. In the present systematic review, we attempted to isolate the independent effect of smoking on TL. All possible efforts were made, employing literature electronic research, manual search, and grey literature, with no date of publication or language restrictions. Although it was not possible to generate a funnel plot, there was a predominance of studies with positive results for TL and smoking, indicating a possible publication bias. Citation bias was also identifiable, since many studies belonged to the same research group.

Thus, regardless of the presence of different risk factors for TL in individuals undergoing PMT, the simple presence of smoking should be a factor to classify individuals undergoing PMT as high risk, determining a short time interval for the recall visits. Additionally, these findings can be used by public health services to create strategies for avoiding smoking initiation and promoting smoking cessation, in order to improve systemic and oral health. However, it is important to highlight the scarcity and the need for well-designed prospective cohort studies, since the GRADE evaluation considered the quality of the scientific evidence moderate.

For future studies, a methodological standardization for the following issues is imperative: (1) characterization of smoking status in terms of both frequency and dose-exposure, and (2) identification of unique dental care protocols and periodontal procedures performed during PMT. Moreover, to minimize heterogeneity, studies with larger samples and longer follow-up periods are necessary.

In conclusion, there is moderate scientific evidence that the independent effect of smoking is associated with the occurrence of TL in individuals undergoing PMT. More prospective longitudinal studies are needed to confirm these findings.

References

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