Abstract
Purpose The health implications related to electronic cigarettes are not fully understood and has created a public health concern. The purpose of this narrative review was to highlight the oral and systemic health concerns associated with electronic cigarettes and compare these concerns to those associated with conventional tobacco cigarettes.
Methods The literature was obtained from PubMed, Ovid Medline, CINAHL, and Scopus databases in June 2021 and updated in February 2023. Sources were chosen based on the following inclusion criteria: date of publication between 2011 and 2023 and written in English. Articles were excluded based on irrelevance to the topic, weak study designs, lack of outcome data, low quality randomized control trials, unavailability of the full text article, and non-empirical research designs. The Cochrane tool, ROBINS-I, was used to assess the risk of bias.
Results A total of 78 studies were included in the review. E-cigarette use was associated with significant adverse effects for cardiovascular, respiratory, immunological, and periodontal health as compared to nonusers; however, impacts were worse with conventional smoked cigarettes. Long term health effects remain unknown with e-cigarettes, but associations have been identified with periodontal and peri-implant disease, oral cancer, and mental health disorders. The heterogeneity of e-cigarette use related to vaping behavior, devices, and liquids limits the ability to generalize results. There is a need for the development of a research standard for exposure methods to establish a consensus with e-cigarette use and support the validity of results among researchers.
Conclusion According to current research, e-cigarettes may induce less harm than traditional tobacco products, but e-cigarettes do not remove the carcinogenic and toxic risk that has been associated with conventional cigarettes. Further research is needed to make broad conclusions on the safety of e-cigarettes compared to conventional cigarettes and to nonusers.
INTRODUCTION
The adverse health effects from conventional smoked tobacco cigarettes were first identified by the Advisory Committee Report to the United States (US) Surgeon General in 1964.1 Smoked tobacco products rank as a leading cause of mortality from ischemic heart disease, respiratory infections, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, and lung cancer.2 To reduce the disease burden induced by conventional tobacco products, electronic cigarettes were introduced in the US around 2004 as a presumptively safer nicotine alternative.2
Electronic cigarettes (e-cigarettes) are defined as a noncombustible form of tobacco and referred to as e-cigs, vapes, vape pens, e-hookahs, tanks, and electronic nicotine delivery systems (ENDS).3 E-cigarettes have become a widespread nicotine alternative within the US in the last decade. According to the Center of Disease Control (CDC), e-cigarettes have become the second most commonly used tobacco product among adults with an estimated 3.7% identified as being users.4 From 2015 to 2018, the total market sales for e-cigarettes increased more than six-fold from $304.2 million to $2.06 billion.5 However, in 2018, the Federal Drug Association (FDA) began regulating e-cigarettes as tobacco products and issued a statement requiring all tobacco products, including e-cigarettes to be labeled with an addictive warning statement.6
Despite these regulations, the e-cigarettes market continued to evolve at a rapid rate and gained popularity particularly among vulnerable populations and is currently the leading tobacco product used among youth and young adults in the US.7 The highest prevalence of e-cigarette use in adults was between the ages of 18–24, and more than half of these individuals had never smoked cigarettes.4 There was a dramatic increase in e-cigarette use among middle schoolers from 0.6% in 2011 to about 11% in 20198 and in 2022, 3.3% of middle school students and 14.1% of high school students had used an e-cigarette in the past 30 days.9 Furthermore, the rate of e-cigarette use was higher for pregnant women (3.6%) than women who weren’t pregnant (3.3%).10 Among women who used e-cigarettes before pregnancy, 25% continued to use e-cigarettes during pregnancy.10
According to the 2020 National Youth Tobacco Survey, e-cigarettes usage has been increasing in terms of frequency which increases the risk for dose-related side effects.8 Since 2019, there has been an emerging epidemic around e-cigarettes with increasing reports of associated pulmonary complications linked to vaping products containing tetrahydrocannabinol (THC).3,11 From March 2019 to January 2020, the CDC began collecting data on e-cigarette and vaping product use-associated lung injury (EVALI) and reported 2,668 cases.11 Several recent studies have also reported increases in vaping behavior, prevalence, and consumption since the COVID-19 pandemic.12-15
The increasing prevalence of e-cigarettes and the associated effects is a public health concern which merits a narrative review of the current research. The purpose of this narrative review of the literature was to highlight the oral and systemic health concerns associated with electronic cigarettes and compare these concerns to those associated with conventional tobacco cigarettes, and determine the risk and severity of disease associated with e-cigarette use.
METHODS
Articles were obtained from electronic databases including PubMed, Ovid Medline, CINAHL, and Scopus. The initial search was conducted in June 2021, followed by an updated search in February 2023. Duplicates were removed before the screening process. Searches were limited by automation tools to screen sources based on English language, publication dates between 2011 and 2023, and full text availability.
The search was conducted using terms including “electronic cigarettes”, “electronic nicotine delivery systems”, “e-cigarettes”, and “electronic cigarettes and conventional smoking”. MeSH terms include “dental”, “oral health”, “periodontal”, “gingival tissue”, and “adverse effects”. Included study designs consisted of randomized controlled trials (RCT), in-vitro, in-vivo, case controls, cross-sectional, and cohort studies. A total of 2,766 search results were screened for relevance based on the title and abstract. A total of 274 articles were retrieved and analyzed for further eligibility.
Inclusion criteria consisted of articles that were available to review and pertained to the use of e-cigarettes exclusively or in comparison to conventional cigarettes. Research that focused on the perception of e-cigarettes or the dual use of e-cigarettes and conventional cigarettes were excluded from the study. Studies that could not validate the exclusive use of e-cigarettes by subjects or lacked a control group were also excluded as the results were inconclusive. Research articles were also excluded for high levels of bias and having a weak study design that was low in external validity.
The articles retrieved were assessed by two reviewers. The risk of bias assessment for each study was completed using Cochrane’s tool, Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I). The assessment criteria contained seven domains where bias might be introduced. Interpretation of the risk of bias using ROBINS-I is summarized in Table I. A total of four studies were classified as having a serious or critical overall risk of bias and were excluded from the review.
Interpretation of the Risk of Bias in ROBINS-I*
Studies that did not report statistical results or provide numerical data were excluded from the synthesis as these studies lacked scientific rigor and had poor justification for conclusive statements. Statistical results that were collected include the level of significance, p-value, mean, standard deviation, and confidence interval. Differences between two groups in a study were reported as statistically significant if the research reported p<0.05. Studies were grouped for synthesis based on similar measures of outcome data and research objectives.
From the 274 studies retrieved, 196 were excluded based on the exclusion criteria; 78 studies were included in the review. The articles were initially evaluated with the intention of a systematic review and for potential meta-analyses both overall and within outcome-specific categories (periodontal disease, oral infections, respiratory outcomes, etc.). Given the heterogeneity in the outcome measures and exposures, it was determined that formal meta-analysis methods were not applicable to this collection of studies. Therefore, results from the 78 included studies were used to formulate a narrative review.
RESULTS
Study results were broadly categorized into one of two main domains, systemic health and oral health, and associated subcategories. Subcategories within systemic health included respiratory health (n=22), cardiovascular health (n=8), neurological development (n=11), immunity (n=2), secondhand smoke (n=4), and pregnancy and infancy (n=4). Subcategories within oral health included periodontal health (n=14), soft and hard tissue lesions (n=7), and oral cancer (n=6). Heterogeneity of the included studies may be due to differences in study designs, exposure methods, subject selection, and/or the outcomes measured. The characteristics of the included studies (n=78) are shown in Table II.
Study Characteristics
Systemic Health
Respiratory Health
Twenty-two studies were related to respiratory health.16-37 Associations were reported with e-cigarette use and higher incidence of asthma,16-21 respiratory disease,22-25 and wheezing26,27 in cross-sectional studies. Ten studies investigated these associations and found e-cigarettes to be linked with several systemic consequences related to pulmonary inflammation.28-37 A low to moderate risk of bias was determined with these studies due to bias with confounding variables and selection bias of participants. A cohort, RCT, and an in-vivo study demonstrated that e-cigarette users had a higher prevalence of respiratory complications with a significant increase in emphysematous lung destruction, respiratory impedance, and peripheral airway resistance when compared to nonusers of e-cigarettes.28-30 Six in-vitro and one in-vivo study investigated the mechanisms of this pro-inflammatory response as related to the incidence of pulmonary injury.31-37 These results demonstrated that e-cigarettes were capable of triggering secretions of cytokines, inflammatory mediators, and growth factors.31-34 The upregulation of certain biomarkers and proteins with e-cigarette exposure was also associated with a significant increase in oxidative stress, apoptotic pathways, and necrosis in pulmonary cells.34,35 In addition, potential contributing factors were identified (chemical flavorings, particulate matter, and nicotine concentration) in e-cigarettes that influenced the release of certain cytokines and cytotoxic outcomes.31-37 When compared to conventional cigarettes, similar physiological changes have been reported, however, e-cigarettes induced significantly lower oxidative stress levels as compared to conventional cigarettes.33,34,36 These studies indicated that e-cigarettes induce cellular and functional changes in pulmonary cells that increase the risk for respiratory complications, however long term effects remain unknown due to a lack of longitudinal studies.31-37
Cardiovascular Health
In the eight studies reviewed, e-cigarette use was associated with an increased risk of cardiovascular implications in two cross-sectional, one RCT, one cohort, two in-vitro, and two in-vivo studies.38-45 There was a low to moderate risk of bias with these studies including recall and selection bias with participants. According to Alzahrani et al., daily e-cigarette use was associated with an increased risk of myocardial infarction (p = 0.004), similar to conventional cigarettes.38 This association was supported by Antoniewicz et al. and Podzolkov et al. by demonstrating that e-cigarettes significantly elevated endothelial progenitor cell levels and albuminuria levels in the blood, indicating a risk for atherosclerosis, cardiac embolism, and strokes.39,40 Similarly, Anderson et al. and Moheimani et al. showed that e-cigarettes adversely affected vascular cells by inducing significant DNA damage, cell death, and oxidative stress.41,42 When compared to conventional cigarettes, e-cigarettes had a lesser impact on vascular function; however, both significantly increased oxidative stress and endothelial dysfunction compared to nonusers.43 One in-vivo and one in-vitro study found these physiological effects to be nicotine independent and dependent.44,45 The fine particulate matter was a major contributor by significantly enhancing platelet activation and aggregation, whereas nicotine significantly impacted cardiovascular structure and function.44,45 Evidence suggests e-cigarettes, similar to conventional cigarettes, are associated with acute cardiovascular abnormalities and the risk of cardiovascular complications increases with its use.39,42
Neurological Development
A total of eleven studies, including five cross-sectional and six prospective cohort studies focused on the neurological impact of e-cigarette use.46-56 These studies had a moderate risk of bias with self-reported outcomes. According to Grant et al., e-cigarette use among university college students was significantly associated with higher levels of alcohol abuse and illicit drug use than nonusers.46 It was also associated with higher risk of subsequent initiation of conventional cigarettes, marijuana, and cocaine use in cohort studies.47-52 When compared to conventional cigarettes, nicotine dependency was found to be two times higher among young adults who smoke e-cigarettes, indicating significant addiction mechanisms associated with vaping.53 Furthermore, e-cigarette use had a significant association with higher rates of post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), anxiety, low self-esteem, and low academic performance among young adults.46,54,55 This psychological distress was associated with both conventional and e-cigarette use.56 These findings suggest that e-cigarettes have an addictive potential with neurological implications that are comparable to conventional cigarettes.46-56 However, longitudinal studies are needed to determine the direction of this association and to evaluate the long term mental health consequences.46-56
Immunity
There were two identified studies regarding immunity with e-cigarette use, an in-vitro and cross-sectional study.57,58 These studies had a moderate risk of bias due to confounding variables with the diversity of e-cigarettes. The prospective cross sectional study by Martin et al., showed an association with e-cigarette use and the reduction in the expression of immune related genes that was significantly greater than conventional cigarette users.57 In addition to gene suppression, Corriden et al. found a significant decrease in chemotaxis and phagocytosis in neutrophils exposed to e-cigarette vapor compared to non-exposed cells.58 In both studies, these immunological effects have been found to have a nicotine independent and dependent effect, indicating that e-cigarettes can suppress the immune system regardless of the nicotine concentration.57,58 The level of immune suppression among e-cigarette users may lead to decreased immune response and increase susceptibility to bacterial infections that may be comparable to conventional cigarettes with long term use.57,58
Secondhand Smoke
Secondhand smoke, also known as passive or sidestream smoking, is the involuntary exposure of bystanders to emissions produced by a vaping device, cigarette, or the exhaled breath of an associated user.59 When studying secondhand exposure, four studies took into consideration the particulate matter and the volatile organic compounds (VOCs) that are released into an environment which may cause short and long term adverse health effects if inhaled.60-63 These studies had a moderate risk of bias due to confounding variables related to differences in vaping and breathing behavior, and e-cigarette devices and liquids used.
The RCT studies conducted by McAuley et al. and Czogala et al. demonstrated that exhaled conventional cigarette smoke was significantly higher in magnitude of pollutants, VOCs, and nicotine concentration than exhaled vapor from e-cigarettes.60,61 These findings were supported by a cohort study showing that the composition of e-cigarette vapor was found to have insignificant amounts of VOCs, indicating less toxicity.62 However, McClelland et al. reported that short term exposure to e-cigarette vapor caused significant rises in oral temperatures among bystanders in comparison to controls, indicating possible oral implications.63 Chronic secondhand exposure to nicotine, propylene glycol, and glycerol in exhaled vapor were also identified as risk factors for respiratory irritation, increased palpitation, and increased systolic blood pressure.61 Therefore, systemic and oral health consequences from secondhand exposure to e-cigarettes cannot be excluded, nor deemed as safe due to the lack of longitudinal studies.60-63
Pregnancy and Infancy
E-cigarette use during pregnancy was an independent risk factor for neonatal complications.64-67 Four studies, two in-vivo, one in-vitro, and one cohort study investigated the safety of e-cigarette use during pregnancy.64-67 Bias among these studies was determined to be low to moderate due to the diversity with e-cigarettes and limitations with subject selection with animal studies.
The cohort study by Kim et al. found that infants exposed to e-cigarettes during gestation were significantly more likely to be small for gestational age, have low birth weight, or be born preterm compared to nonusers; this significance was similar to conventional cigarettes.64 However, these findings were contradicted by the in-vivo animal studies which demonstrated no significant decrease in the weight of offspring exposed to e-cigarettes.65,66 Despite this difference, the in-vivo studies found a significant increase (p=0.02) in neurological development and changes in gene expression resulting in adverse neurobehavioral outcomes in offspring exposed to e-cigarettes.65,66 E-cigarette exposure was also found to impair development and promote inflammation in the lungs of offspring, but to a lesser extent as compared to conventional cigarettes.67 There was also nicotine independent and dependent effects, indicating that the components of e-cigarettes, other than nicotine, can have a detrimental impact affecting neurodevelopment and lung growth in infants during gestation.66,67 Findings from these studies do not support e-cigarettes as an alternative to conventional cigarettes during pregnancy, rather it is advised to abstain from both conventional and e-cigarettes during gestation.64-67
Oral Health
Periodontal Health
A total of fourteen studies assessed the risk of e-cigarette use on periodontal disease. Six investigated the association of e-cigarettes and periodontal disease,68-73 five were on the cytotoxicity and the pro-inflammatory mechanism,74-78 and three focused on peri-implant disease.79-81 Bias among studies ranged from low to moderate and results varied between studies depending on the e-cigarette device, e-liquid, and exposure method used.
Study results identified that e-cigarette users had an increased risk of periodontal disease, tooth loss, and bone loss compared to nonusers but at a significantly slower rate when compared to conventional cigarettes.68-70 Two cohort studies investigated this association and concluded that e-cigarettes induce oral microbial dysbiosis by enhancing the growth of opportunistic pathogens, similar to conventional cigarettes.71,72 Other studies have suggested a pro-inflammatory response, showing e-cigarettes increase inflammatory mediators and periodontal cytokines related to the pathogenesis of periodontal disease.74-76 Similarly, there have been reported cytotoxicity effects including DNA damage, apoptosis, reduced metabolic activity, and decreased cell vitality and proliferation in oral cells exposed to e-cigarette vapor.74-78 Several inflammatory responses have also been independent of nicotine concentration, indicating an association with flavoring agents and particulate matter.75,76 However, advanced periodontal disease and tooth loss was associated with chronic long term use of e-cigarettes with nicotine.73 The adverse cellular effects induced by e-cigarettes may contribute to the onset of periodontal disease or exacerbate its severity with chronic use.74-78
Studies with dental implants showed significant positive correlation between e-cigarette usage and marginal bone loss, increased probing depths, and plaque index when compared to nonusers.79-81 These findings have been found to be independent of nicotine concentration, indicating possible deleterious effects associated with e-liquid flavors and other contents on implant materials.81 These studies have indicated adverse effects of e-cigarettes on osseointegration and implant health and that can be comparable to conventional cigarettes.79-81 Future studies are warranted by these findings to validate the association between e-cigarettes and peri-implant disease.
Soft and Hard Tissue Lesions
E-cigarette use has been associated with hard and soft tissue lesions in the oral cavity and seven studies were reviewed regarding these associations.82-88 Three studies evaluated soft tissue lesions related to e-cigarette use with low to moderate risk of recall bias with self-reported oral symptoms and confounding variables.82-84 An in-vitro study demonstrated cells exposed to e-cigarettes, despite nicotine content, significantly increased the growth of Candida Albicans, and the risk for oral fungal infections.82 When compared to conventional cigarettes, this risk was found to be less significant.82 However, a case control study showed that e-cigarette users have reported significant increase in soft tissue lesions compared to nonusers, including hyperplastic candidiasis, black hairy tongue, and nicotine stomatitis.83 A cross-sectional study reported e-cigarette use was significantly associated with cracked or broken teeth, tongue and mucosal pain, and gingival bleeding.84 Although the risk and severity of soft tissue lesions may be lower with e-cigarette use compared to conventional cigarettes, it is still more significant than nonusers and is not advised as safe.82-84
Two in-vitro and two cross sectional studies have shown that e-liquid flavorings have a significant effect on oral hard tissue.85-88 There was a low to moderate risk of bias with representing the complexity of the oral microbiome and controlling for confounding variables related to the diet, oral hygiene, and genetic variation of subjects. Two cross-sectional studies found vaping to be associated with a higher caries risk and an increase in untreated decay.85,86 Kim et al. supported this association by reporting a significant cariogenic risk induced with e-cigarettes.87 The aerosols produced by e-cigarettes release minerals and metals such as calcium, iron, and copper which have been shown to facilitate the growth of biofilm in the oral cavity and adherence of Streptococcus Mutans to the enamel.87 In addition, the saccharides and acidic compounds in e-cigarette flavors promoted bacteria metabolism and initiated enamel demineralization.87 Pintado-Palomino et al. also found significant enamel staining with menthol and tobacco flavor liquids, concluding that the flavor of e-liquid had greater influence on enamel staining than nicotine content.88 These studies concluded that e-cigarettes pose a risk for dental health.85-88
Cancer
Six studies, one in-vivo and five in-vitro, examined the risk of cancer with e-cigarette use, and reported low to moderate risk of bias with the lack of longitudinal studies.89-94 Four studies reported significant adverse DNA alterations in cells exposed to e-cigarette vapor compared to nonusers.89-92 DNA damage was found to be dose-dependent on e-cigarette liquid, but independent of nicotine content.90,92 The e-liquids varied in their effect, with some flavors significantly increasing cell invasion and inflammation with oral squamous cell carcinoma.93 Other studies have shown nicotine in e-cigarettes having significant negative short term effects on cellular viability and proliferation, which may contribute to apoptosis in the long term.94
When compared to conventional cigarettes, DNA damage and gene deregulation was significantly less with e-cigarettes.90,91 However, the amount of DNA double strand breaks was found to be similar between e-cigarettes and conventional cigarettes and was significant when compared to nonusers.92 These studies demonstrated significant short term DNA damage with e-cigarette exposure which may become more pronounced over time and increase the risk for tumorigenesis and cancer-related outcomes with long term use.89-94
DISCUSSION
This broad review of research highlights recent studies to inform health professionals and the public on the widespread concerns regarding e-cigarette use. According to recent reports, a majority of dental and medical students did not feel confident with their knowledge on e-cigarettes and their ability to discuss the related oral and systemic health consequences.95-97 Health care professionals have also reported a need for clinical education related to vaping.98 The lack of knowledge among dental and medical students and need for longitudinal studies on e-cigarettes warrants future research and educational initiatives.
This review extends prior reviews by interpreting evidence for a variety of systemic and oral health conditions, while also incorporating additional evidence to compare with conventional cigarettes. Results identified in this review are consistent with those in prior reviews99-107 indicating that e-cigarettes reduce lung function, increase arterial stiffness, induce immunological alterations, and increase risk for acute coronary syndromes.99,100 Other recent reviews have reported negative mental health associations with e-cigarette use including alcohol abuse, anxiety, depression, and increased nicotine dependence.101-103 These similar results have suggested the possible psychological effects that may diminish the quality of life for e-cigarette users.
Oral health implications of e-cigarette use have also been consistently reported in previous reviews.104-107 Recent reviews have reported an increase in periodontal attachment loss, radiographic bone loss, plaque index, and probing depths with vaping; however, there is not enough clinical and longitudinal evidence to validate causation.104-106 Flach et al. reported the possible carcinogenic effects and risk for head and neck cancer with chronic e-cigarette use, but evidence is limited to in-vivo and in-vitro studies.107 There is a critical need for the development of clinical studies to investigate this association to understand the extent to which e-cigarettes impact oral health.
Some caution is needed when interpreting results from this review. The search strategy consisted of full text articles in English language, therefore, research published in other languages may have been omitted. Studies were also diverse in exposure methods and outcome measures which prevented a systematic review with meta-analysis from being performed. Consensus regarding e-cigarette use has been challenging to establish due to the heterogeneity among vaping behaviors, devices, and liquids. Developing a standard exposure method related to the frequency of use, volume of liquid consumed, and nicotine concentration can help improve validity and reliability of results among the various research studies. There is also a lack of longitudinal studies available considering that e-cigarettes first emerged as a popular tobacco product in 2014.108 Therefore, firm conclusions about causation and long-term effects could not be inferred.
Several limitations also reside with the study designs. Due to ethical reasons, 31 studies were in-vivo and in-vitro. It is necessary to interpret this data with caution as these results do not replicate the human environment and physiological interactions exactly. Future clinical trials and observational studies are needed to validate these findings. There is also a lack of RCTs as utilization of human participants is often unethical, difficult, or impossible to incorporate. As a result, participants were commonly recruited on a volunteer basis or by an interview process that resulted in selection bias. In addition, several studies relied on self-reported outcomes and questionnaires, increasing the risk of recall bias. Because of the high variability with e-cigarettes, the level of severity of the effects may vary depending on the type of device, flavoring content, nicotine concentration, and exposure time. Therefore, the ability to generalize results from one e-cigarette product to the whole population of e-cigarettes may not be representative of the diversity of vaping products available.
CONCLUSION
There is a critical need for observational and longitudinal studies to ascertain the long-term effects of vaping on systemic and oral health. Prospective and retrospective longitudinal cohort studies could be ethically conducted by acquiring subjects on a volunteer basis with a history of e-cigarette use. Future case control or cohort studies with larger sample sizes are also needed to establish a causal relationship between e-cigarettes and oral and systemic diseases. Further research is needed to make broad conclusions on the safety of e-cigarettes compared to conventional cigarettes and to nonusers. According to current research, e-cigarettes may induce less harm but these products do not remove the carcinogenic and toxic risk that has been associated with conventional cigarettes.
Footnotes
NDHRA priority area, Population level: Health services (epidemiology).
- Received October 19, 2022.
- Accepted May 30, 2023.
- Copyright © 2023 The American Dental Hygienists’ Association
This article is open access and may not be copied, distributed or modified without written permission from the American Dental Hygienists’ Association.
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