The impact of vaping on periodontitis: A systematic review

Abstract Background and objective While tobacco cigarette smoking has been proven to be a risk factor for periodontitis, limited information is available regarding vaping, a new alternative to smoking that has been branded as less harmful. Several important in vitro studies have shown that vaping has a similarly damaging effect as cigarette smoking on the health of the periodontium. However, a comprehensive review is lacking in this field. Therefore, we aimed to systematically review the literature about the impact of vaping on periodontitis. Methods The research question was created using the PICOs format. A systematic search of the following electronic databases was performed up to March 2020: Medline, Embase, PubMed, Cochrane, and grey literature. Human studies that assessed periodontal status (plaque index, bleeding on probing, clinical attachment loss, marginal bone loss, and probing depth) in e‐cigarette users compared to non‐smokers (control group) were assessed based on an estimate of fixed effects. The weights of the studies were calculated based on their risks of bias. Results After duplicates were removed, 1,659 studies were screened and 8 case–control studies that investigated the relationship between vaping and periodontal parameters in humans were selected after their risk of bias assessment. Estimated effects of vaping after weighting results based on their standard deviation showed increased plaque, marginal bone loss, clinical attachment loss, pocket depth, and reduced bleeding on probing. Conclusion This study concluded that there is not enough evidence to fully characterize the impacts of vaping on periodontitis. However, within the limitations of our review and the selected included studies, the available results point to increased destruction of the periodontium leading to the development of the disease.


| INTRODUCTION
Periodontal diseases are defined as an inflammatory process associated with bacterial activity and mediated by the host's immunologic response (Armitage, 1999;Tonetti et al., 2018). This aggression may result in the loss of connective tissue attachment and consequently bone loss (Armitage, 1999;Tonetti et al., 2018). Gingivitis, a reversible form of periodontal disease, is initially characterized by gingival inflammation caused [Correction added on 30 December 2020, after Online publication: First and third author affiliations have been corrected in this current version.] by bacterial colonization forming the biofilm (Armitage, 1999;Tonetti et al., 2018). In susceptible individuals, gingivitis may progress to an irreversible form of the disease, periodontitis, where there is the loss of periodontal ligament and apical migration of the junctional epithelium (Armitage, 1999;Tonetti et al., 2018). Risk factors, such as diabetes, genetics, and smoking, have been related to the susceptibility, prevalence, and severity of the disease (Armitage, 1999;Tonetti et al., 2018).
It is well established that cigarette smoking is considered as a risk factor in the development of periodontitis (Armitage, 1999;Leite et al., 2018;Tonetti et al., 2018). It has been shown that patients who smoke suffer from more severe forms of periodontitis (Javed et al., 2013). Disease progression is directly related to the frequency of smoking, where heavy smokers show more severe forms of the disease compared to light smokers (Tonetti et al., 2018). Different studies categorize the frequency of smoking differently but according to one review, smoking less than 9 cigarettes per day is considered light, and more than 31 is considered heavy smoking (Johnson & Guthmiller, 2000). A recent systematic review with meta-analysis showed that smoking increases the risk of developing periodontitis by 85% (Leite et al., 2018). Smoking also impacts the response to periodontal treatment; smokers show only 50%-75% improvement in their clinical parameters after scaling and root planing compared to non-smokers (Tonetti et al., 2018). Another study analyzed the effects of cigarette smoking on periodontal parameters and found significant increases in plaque index, pocket depth, and clinical attachment loss levels in cigarette smokers compared to non-smokers (Javed et al., 2017). It has been evidenced that tobacco smoking results in a proinflammatory effect by stimulating the secretion of specific cytokines and radical oxygen species (ROS) that play a role in the destruction of periodontal tissues (Katz et al., 2005).
Vaping electronic cigarettes (e-cigarettes) have grown into a popular recreational activity among teenagers and young adults in Canada in the last few years. Since the Tobacco and Vaping Products Act (TVPA) became legal in Canada in May 2018, adults have the right to purchase vaping products with nicotine as an allegedly less harmful option than smoking (Government of Canada: Smoking, Vaping, and Tobacco, 2020). Instead of burning tobacco, as traditional cigarettes do, e-cigarettes heat up and vaporize nicotine or other flavoring products that might be included in it. The Canadian Tobacco, Alcohol and Drugs Survey conducted on students between grades 7 and 12 between 2016 and 2017 concluded that 23% of students in grades 7-12 had tried a vaping product at least once. Ten percent reported using them within the last 30 days and 53% of all students thought it would be" fairly easy" or" very easy" to get a vaping product if they wanted one (Government of Canada: Smoking, Vaping, and Tobacco, 2020). Interestingly, while 74% of current smokers recognize a great risk in smoking traditional cigarettes regularly, only 24% of current vape users recognize risk in vaping electronic cigarettes.
The literature on vaping e-cigarettes has shown that there are systemic impacts of vaping (Gaur & Agnihotri, 2019;Government of Canada: Smoking and Oral Cancer, 2011). Vaping with nicotine exposes users to nicotine addiction and side effects such as altered teen brain development and cognitive and behavioral problems (Government of Canada: Smoking and Oral Cancer, 2011). Vaping without nicotine still proposes risks of exposure to the chemicals that are released in the heating process of the device, such as aluminum, copper, and lead (Gaur & Agnihotri, 2019). E-cigarettes also pose a hazard for traumatic injuries. Blast injuries caused by battery explosion are also an associated risk, mainly in countries where there is no regulation on the manufacture and safety of e-cigarettes (Kite et al., 2016). An in vitro study correlated e-cigarette aerosol exposure to DNA damage and mitochondrial dysfunction in lung fibroblasts (Lerner et al., 2016). Another study compared the effects of cigarette smoke and e-cigarette aerosol in bone marrow-derived mesenchymal stem cells and found that e-cigarette aerosol exposure causes overproduction of ROS (Shaito et al., 2017).
Focusing on a correlation between oral health and vaping, a recent study showed that e-cigarette exposure-mediated carbonyl stress leads to increased levels of prostaglandin-E2 and cyclooxygenase-2 in human gingival epithelium compared to control (Lerner et al., 2015). Several

| Eligibility criteria
This systematic review only included human studies that investigated an association between vaping and periodontal status in a clinical context. Studies that included parameters such as plaque index (PI), bleeding on probing (BOP), clinical attachment loss (CAL), probing depth (PD), and marginal bone loss (MBL) were included. Also, these studies included patients who did not receive periodontal treatment 6 months before the study. No age or sex restrictions were applied.

| Exclusion criteria
Descriptive studies, case reports, case series, abstracts, systematic/ scope reviews, and expert opinions were not included. Exclusion criteria for patients: pregnancy, current cigarette smokers, waterpipe smokers, or smokeless tobacco users, immunocompromised patients, diabetic patients, patients who went through periodontal therapy during the last 6 months, patients taking anti-inflammatory or antibiotic medication, and edentulous patients.

| PICO
The researchable question was created using the PICOs (Population, Intervention, Comparison, Outcome) format. Population: Group A inclusion criteria: Participants who are not using any form of tobacco; ages 13 and up. Group B inclusion criteria: Participants who reported vaping e-cigarettes for at least 1 year before the study. Intervention: History of vaping of e-cigarettes. Comparison: Non-smokers. Outcomes: Presence of periodontal disease as indicated by increased probing depth, attachment loss, gingival recession, and bone resorption.

| Search strategy
A systematic search of the following electronic databases was performed up to March 2020: Medline, Embase, PubMed, and Cochrane.
Additional information about vaping laws and prevalence statistics were obtained from the Canadian government website. The search was restricted to the English language and no year restriction was applied. The search strategy used tried to include all terminology that refers to electronic cigarettes and periodontal parameters.

| Study selection
A two-phase process to select the final articles was followed. In the first phase, two reviewers (CF and RC) independently screened titles and abstracts from all gathered references. In the second phase, fulltext articles were assessed by reviewers to confirm their final selection. In the case of disagreements, the consensus was reached after discussion, a third person (NA) was involved when necessary.

| Risk of bias in individual studies
The studies were evaluated by 2 reviewers following The Joanna Briggs Institute (JBI) critical appraisal checklist tool (Joanna Briggs Institute critical appraisal tools, 2017). The critical appraisal checklist tool for analytical cross-sectional studies was used to assess the risk of bias. This tool of assessment describes the following main components: true random sequence generation, allocation concealment, blinded outcome assessment, selective outcome assessment, and appropriate statistical analysis. Studies would be assigned to the highest risk of bias if the sequence generation and allocation concealment were unclear.  The studies that were not included due to full-text assessment were excluded due to irrelevant study design, comparison, intervention, or population.

| Study characteristics
Study characteristics are reported in Table 1

| Risk of bias within studies
The Joanna Briggs Institute assessment tool for risk of bias of crosssectional studies was used, results are reported in Table 2 (Joanna Briggs Institute critical appraisal tools, 2017). The risk of bias was categorized as high if the percentage of yes is equal or lower than 49, moderate if the percentage of yes was between 50% and 69%, and low if the percentage of yes was equal or higher than 70%. Following these criteria, four of the included studies were at low risk of bias and the other four at moderate risk of bias.

| Results of individual studies
All extracted results from included studies that compared the periodontal status of vape users and non-smokers can be found in Table 3. These studies looked at differences between PI, BOP, CAL, PD, MBL mesial, and MBL distal. The linear comparison of these results is shown in Figures 2 to 7. The results in Table 3 Vohra et al., 2020). With exemption to one study which showed no difference between the two groups, all other results for CAL were increased in vaping groups (Vohra et al., 2020). This indicated that subjects who vaped consistently showed more loss of clinical attachment compared to non-smokers. Differences in probing depth Overall results except for two studies showed increased values in the vaping groups (Javed et al., 2017;Vohra et al., 2020). Interestingly, one study reported mild changes in all periodontal parameters related to vaping (Vohra et al., 2020). This was the only study that was found to show this phenomenon. Most of the studies, as it can be seen from (p < .0001) less, for PI was 13.32% (p < .015) more, for CAL was 0.2 mm more (p < .5), for PD in % greater than 4 mm was 3.26% more (p < .2), PD in mm was 1.18 mm more (p < .03) for MBL mesial was 0.19 mm more (p < .4) and MBL distal was 0.12 mm more (p < .7).

| DISCUSSION
This was the first review conducted to assess the impact of vaping on periodontitis by investigating the changes in periodontal parameters in vape users compared to control groups. Several recent studies have illustrated the effects of vaping on periodontal parameters and we found it relevant to the dental community to have their results 14.3 ± 1.2 daily frequency and 3.5 ± 0.6 years of duration.
Note: All studies were carried out in Saudi Arabia and had a case-control design.
T A B L E 2 Joanna Briggs Institute risk of bias tool for cross-sectional studies Author Q1* Q2* Q3* Q4* Q5* Q6* Q7* Q8* %Yes  have results closer to non-smokers than smokers do (Javed et al., 2017;Subhi et al., 2019). This goes following the results we are seeing in this review, wherewith combined results, vape users did not have exacerbated differences from non-smokers.
However, there are potentially harmful effects of vaping in general health that should be considered. Besides the previously mentioned metals present in the aerosol, blast injuries, DNA damage, and overproduction of ROS (Kite et al., 2016;Lerner et al., 2016;Shaito et al., 2017), vaping have been linked to cases of severe pulmonary disease in the US (Hammond, 2019).
For the statistical analysis of the extracted results, we assigned weights to each study inversely proportional to their standard deviation. Two of the included studies were assigned the highest weights (Javed et al., 2017;Mokeem et al., 2018). These studies assess CAL, which would be the measurements of choice to detect periodontitis as suggested by the latest classification (Tonetti et al., 2018 properties (Silverstein, 1992). A reduction is BOP is a rather negative effect than positive, as gingival bleeding is a symptom that could alarm Arabia. It must also be noted that in this region, shisha smoking is a very popular activity, and could have influenced these studies results.
More studies from different regions are needed to better understand the impacts of vaping on periodontitis.

| CONCLUSION
The effects reported in this review are relatively non-significant in a clinical context, however, as mentioned earlier, these results should be interpreted with caution, as four of the eight included studies fell into the moderate risk of bias. Although there is not enough evidence to fully characterize the impacts of vaping on periodontitis, the available results point to an unhealthy impact of vaping in the disease, which calls for further clinical studies to assess the effects of vaping on periodontitis longitudinally.