Denise Thieleman, BS
Christina Tulloch, BS
Joan Pellegrini, PhD, BSDH, MSDH, RDH
Abstract
Objective: Conventional cigarettes have shown severe toxicity on immune cells and wound healing in the periodontium, but little is known about the comparative effects of vaping or electronic cigarettes. In a substantial shift away from conventional cigarettes, vaping and e-cigarette sales have increased nearly 600% since 2017. If current conventional cigarette users are to transition to a less detrimental alternative, the evidence must demonstrate if electronic nicotine delivery systems can be deemed safer than conventional options.
Methods: By compiling data from the PubMed database, the most recent perspectives on new smoking methods and effects of usage on periodontal tissues were examined. The authors input various combinations of MeSH terms: “electronic nicotine delivery system,” “periodontal,” “gingival,” and “electronic cigarette.” Search results were filtered to include only studies within the last five years, included all countries, and selective preference was given to primary research sources.
Results: Electronic nicotine delivery systems have been shown to contribute to several pathophysiological effects including oxidative and carbonyl stress, inflammatory dysfunction, presence of apoptotic necrotic epithelial cells, and impaired fibroblastic activity. Evidence-based research has shown the use of electronic nicotine devices leads to changes in cellular activity, which manifests as a strong risk factor for periodontal disease and fibrosis of the oral submucosa. The primary outcome measure of the health of the periodontium was indicated mainly by bleeding on probing, attachment loss, and presence of inflammatory cells.
Conclusion: Electronic nicotine delivery systems are still being studied, and studies are difficult to complete due to participants partaking in multiple forms of smoking. Although individuals transitioning from conventional to newer electronic nicotine delivery devices perceive it as a healthy switch, scientific evidence indicates the risk of periodontal damage and disease is significant.
Introduction
Electronic nicotine delivery systems (ENDS) are devices capable of converting a liquid mixture containing flavoring and concentrated nicotine to a vapor, which is inhaled. ENDS vapors are comprised of several chemicals (propylene glycol, vegetable glycerin, aldehydes), heavy metals (nickel, chromium, silver, copper), ultrafine/nanoparticles, diacetyl, 2,3-pentanedione, and acetoin.1 The vapors pose a risk to periodontal tissue health and induce oxidative stress leading to the release of destructive inflammatory cytokines.1 The release of destructive inflammatory cytokines and induction of oxidative stress increases the user’s risk for periodontal disease and permanent destruction to the periodontium.
Since the release of the devices in 2006, research indicates ENDS are not a safer alternative to conventional cigarettes due to the estimated 7,000 chemicals contained in the vapors, many of which have limited or insufficient research regarding the health effects when inhaled.2 Studies revealed the regulation of ENDS manufacturers has been overlooked, creating more concerns in the scientific field due to the variety of chemicals and metals used in production.2 The increased use of ENDS in younger populations poses a risk to systemic and oral health diseases at an earlier age, possibly leading to irreversible systemic and periodontium damage. The use of ENDS has increased in the United States, particularly among young adults. According to the CDC, in 2018, more than 3.8 million middle and high school students admitted to using ENDS in the past 30 days. Among ENDS users ages 18-24, 40% had never been smokers.3 The increasing prevalence of ENDS use is a public health concern and is a trending area of focus for researchers. The dangers of ENDS are still being studied but so far studies show ENDS are not a safer alternative to conventional cigarettes. ENDS in some respects may be more harmful due to the vapor contents containing various aldehydes, including acrolein and formaldehyde, resulting in damage to DNA as well as delayed and impaired wound healing.4 The contribution of conventional cigarettes to the progression of periodontal disease is well known. But there are currently few studies outlining the information regarding the use of ENDS and the effects on the periodontium. The aim of this review of literature is to analyze and summarize the available evidence concerning the effects of ENDS on the periodontium.
Literature search
The PICO search format was used to formulate this review. The authors sought to answer the question: For patients who use electronic nicotine delivery systems, will the periodontal health be negatively affected compared to those who do not use any forms of nicotine?
Search strategy
Literature was searched using private as well as governmental agency databases including PubMed and Cochrane for studies within the last five years. Results were limited to peer-reviewed journals, primary research reports, and systematic reviews. The search was limited to the English language and was conducted between January 17 and February 27, 2019.
Search terms
Medical Subject Headings (MeSH) terms used for search input were “electronic nicotine delivery systems” or “e-cigarette”; and “interleukin-6” or “fibroblast”; and “periodontal” or “oral.” These same search terms were used for both PubMed and the Cochrane Library.
Assessment quality
The authors selected studies devoid of self-reported or inherent bias, published within the last five years, with statistically significant results. The website analysis form was utilized for all secondary literature not published by a governmental organization or database to determine credibility of the source.
Discussion
This review investigated the effect of ENDS with regard to changes in the activity of inflammatory, innate immune cells, fibroblasts, and connective tissue. The effects on fibroblasts can cause disruption in repairing extracellular matrices and collagen, which are essential for tissue repair. Heavy metal exposure from ENDS is a concern as it has been shown to provoke dysregulation in periodontal cells.5,6 Inflammatory cells release cytokines, which play a role in host defenses to oral bacterial challenge. When inflammatory cells are damaged, the host exhibits impaired ability to recruit the proper cells for healing.7 The changes occurring in the periodontium from using ENDS have ramifications on systemic health and oral health. Conventional cigarette smokers may display less gingival inflammation due to the disruption in the inflammatory response and gingival bleeding whereas ENDS may show an increase in bleeding on probing and slight inflammation due to the contents in the vapor.8 It is important to note the change in gingival health when comparing conventional cigarette use to ENDS use. Providers who treat patients utilizing ENDS should have a protocol to assess and inform the patient of the health implications. The studies featured in this review were not performed over long periods of time, and the authors recommend future longitudinal studies be performed to show a significant and irrefutable association between the use of ENDS and deleterious effects on the periodontium. While ENDS use is on the rise—with one in five high school students partaking—the CDC does not recommend the use for teens, preteens, or pregnant individuals due to the possibility of addiction and damage to the developing brain. As prospective licensed health-care professionals, the authors acknowledge the importance of information regarding the specific, evidence-based pathophysiological changes attributable to ENDS use.
Inflammation and alveolar bone loss
ENDS contain unregulated amounts of aldehydes.1 These compounds, found in the flavoring liquids, have demonstrated nocuous effects on DNA and cellular growth, and have the capability to induce carbonyl/oxidative stress.9 The clinical result of these cellular changes is an increase in the severity of chronic inflammation, classically associated with periodontal disease. The influences of smoking, including ENDS, on the periodontium lead to impaired chemotaxis and phagocytosis, decreased levels of immunoglobulins leading to a decrease in antibody production, increased release of collagenase leading to destruction of soft tissue, and an increased RANKL/osteoprotegerin (OPG) ratio leading to bone resorption. All of these are classic conditions for periodontal disease. Flavored ENDS vapors elicit periodontal fibroblasts to release detrimental levels of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β).10 A dysregulated tissue concentration of these cytokines indirectly contributes to alveolar bone resorption and tissue degradation. In addition, levels of prostaglandin-e2 (PGE2) and cyclooxygenase-2 (COX-2) were found to be increased after using flavored vapor, and these molecules can further contribute to cytokine imbalance.9
The concentrated nicotine atomized into vapor can quickly enter the bloodstream, causing systemic effects on the body. Inhalation of nicotine has been shown to be higher with ENDS use versus conventional cigarettes.11 Nicotine has been shown to directly inhibit the potential of human periodontal ligament cells, thereby reducing normal osteogenesis.12 Similar results have been achieved in animal studies, allowing researchers to directly observe these histological changes.13,14
Heavy metal exposure
ENDS were invented in China, and the majority of units are currently manufactured there, which raises concerns over quality control.15 The metal alloys in the units can be exposed to high levels of heat and voltage, causing several trace metals to be released into the vapor.16 Aside from the systemic effects caused by arsenic, copper, silver, chromium, cadmium, and lead,16 these trace metals have been shown to negatively affect the periodontium. Researchers have established a statistically significant correlation between serum lead levels and periodontitis,5 although more research is warranted to isolate lead exposure from other confounding factors shown to increase risk of periodontitis. Cadmium exposure has a significant association with periodontitis and significantly impacts clinical attachment levels.6 Cadmium has been shown to trigger bone loss via affected osteoclast function.6 Heavy metal exposure from ENDS has proven to be higher than exposure from conventional cigarettes.16 This poses concerns regarding the potential risks to the periodontium in the form of clinical attachment loss, and these investigators believe further research is warranted.
It is important to mention that many patients have allergies to substances found in ENDS. Nickel alloys, found in many devices, can trigger an allergic reaction,17 which the authors hypothesize can acutely contribute to periodontal disease with an increase in localized inflammation. Thermal damage to the periodontium may occur, as ENDS have been documented to malfunction, overheat, and explode.18 Menthol is a common flavoring additive in ENDS liquids and is an allergen with the ability to produce a dermal reaction and inflammation.17 At the time of publication, over 8,000 unique e-liquids have been registered with the FDA.19 Due to the extremely diverse selection of liquids and the comparably scant amount of data, more studies are required to puzzle out the individual effects of e-liquid components.
Fibroblastic sensitivity and apoptotic cells
Not only is menthol an allergen, but it also has been shown to have destructive effects on periodontal ligament fibroblasts with regard to cell migration and growth inhibition.15 Without properly functioning fibroblasts (the predominant cells in the periodontium), one can expect to observe poor wound healing in the mouth and enhancement in severity of periodontitis. Periodontal ligament fibroblasts are more susceptible to the negative effects of ENDS vapor than gingival fibroblasts.20 Researchers have found conventional cigarettes to have a greater effect on fibroblast cytotoxicity than ENDS.20 However, potentially harmful flavorings such as menthol or cinnamon15 were not investigated. Arecoline, a chemical found in ENDS vapor, has been shown to induce fibroblast proliferation by the up-regulation of growth factors expression and endothelial necrotitis. It is thought that ENDS play a role in the progression of oral submucous fibrosis (OSF). OSF is a chronic, potentially malignant disorder described by advanced submucosal fibrosis of oral tissues, contributing to oral disease and pathology.21 Nicotine, which is a main component in ENDS vapor, has been found to cause oxidative stress in periodontal fibroblasts, especially in combination with Porphyromonas gingivalis lysate.22 Studies have demonstrated elevated L-lactate dehydrogenase (LDH) levels, indicating damage to oral tissue cells after exposure to ENDS vapor.15,23 Interestingly, ENDS were found to cause gingival epithelial cells to adopt an atypical morphology, and increasing exposure to vapor was correlated with increasing amounts of apoptotic gingival epithelial cells.23 The reputation of ENDS being safer than conventional cigarettes is counterfactual, as ENDS can significantly contribute to periodontal disease via cellular dysfunction and destruction.
Conclusion
Periodontal ligament fibroblasts, connective tissue, and gingival epithelial cells are the most abundant structural cells in the periodontium; all play critical roles in periodontal regeneration.1 When these cells are destroyed, stimulated by stress, or exposed to unnatural elements, they are unable to incite and maintain normal inflammatory responses.24 Numerous studies over the past several years have made stronger correlations to the effects of conventional cigarette smoking on the periodontium.25 A systematic review/meta-regression has linked smoking to increased risk of tooth loss, periodontal attachment loss, deeper periodontal pockets, and more expansive alveolar bone loss.25 ENDS vapor and conventional cigarettes, especially with flavoring chemicals, have been shown to contribute to the pathogenesis of periodontal disease as well as dysregulated repair responses. The damage done to myofibroblasts can affect the patient’s ability to heal properly due to the decrease in wound contraction. The research explored in this review shows an association between ENDS and detrimental effects on the periodontal tissues as well as the inflammatory immune response.7 However, further studies should be performed to establish a stronger association between vaporized metals and chemicals found in ENDS and the effects on the periodontium. The studies performed in the future should aid in assisting public health officials and health-care providers to deliver the appropriate message about ENDS safety and will serve as a guide for future regulatory measures.
Competing interests
The authors declare they have no competing interests.
References1. Mokeem SA, Alasqah MN, Michelogiannakis D, Al-Kheraif AA, Romanos GE, Javed F. Clinical and radiographic periodontal status and whole salivary cotinine, IL-1β and IL-6 levels in cigarette- and waterpipe-smokers and E-cig users. Environ Toxicol Pharmacol. 2018;61:38–43.
2. Lisko JG, Tran H, Stanfill SB, Blount BC, Watson CH. Chemical composition and evaluation of nicotine, tobacco alkaloids, pH, and selected flavors in e-cigarette cartridges and refill solutions. Nicotine & Tobacco Res. 2015;17(10):1270–1278.
3. Centers for Disease Control and Prevention. (2019). CDC Works 24/7 https://www.cdc.gov/index.htm. Accessed February 17, 2019.
4. Cheng T. Chemical evaluation of electronic cigarettes. Tobacco Control. 2014;23: 11–17.
5. Peyyala R, Emecen-Huja P, Ebersole JL. Environmental lead effects on gene expression in oral epithelial cells. J Periodont Res. 2018;53(6):961–71.
6. Browar A, Koufos E, Wei Y, Leavitt L, Prozialeck W, Edwards J. Cadmium exposure disrupts periodontal bone in experimental animals: implications for periodontal disease in humans. Toxics. 2018;6(2):32.
7. Arrejaie AS, Al-Aali KA, Alrabiah M, Vohra F, Mokeem SA, Basunbul G, et al. Proinflammatory cytokine levels and peri-implant parameters among cigarette smokers, individuals vaping electronic cigarettes, and non-smokers. J Periodontol. 2018;1–9.
8. Wadia R, Booth V, Yap HF, Moyes DL. A pilot study of the gingival response when smokers switch from smoking to vaping. Br Dent J. 2016;221(11):722–6.
9. Sundar IK, Javed F, Romanos GE, Rahman I. E-cigarettes and flavorings induce inflammatory and pro-senescence responses in oral epithelial cells and periodontal fibroblasts. Oncotarget. 2016;7(47).
10. Al-Aali KA, Alrabiah M, Arrejaie AS, Abduljabbar T, Vohra F, Akram Z. Peri-implant parameters, tumor necrosis factor-alpha, and interleukin-1 beta levels in vaping individuals. Clin Implant Dent Related Res. 2018;20(3):410–5.
11. Ramôa CP, Hiler MM, Spindle TR, Lopez AA, Karaoghlanian N, Lipato T, et al. Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report. Tobacco Control. 2015;25(e1).
12. Yu W, Hu B, Shi X, Cao Z, Ren M, He Z, et al. Nicotine inhibits osteogenic differentiation of human periodontal ligament cells under cyclic tensile stress through canonical Wnt pathway and α7 nicotinic acetylcholine receptor. J Periodont Res. 2018;53(4):555–64.
13. Ispas A, Mihu CM, Crăciun AM, Constantiniuc M. Morpho-histological assessment of the periodontal support structures under the action of excessive occlusal forces and under the influence of nicotine. Rom J Morphol Embryol. 2018;59(1):211–217.
14. Ramôa CP, Eissenberg T, Sahingur SE. Increasing popularity of waterpipe tobacco smoking and electronic cigarette use: Implications for oral healthcare. J Periodont Res. 2017;52(5):813–23.
15. Willershausen I, Wolf T, Weyer V, Sader R, Ghanaati S, Willershausen B. Influence of E-smoking liquids on human periodontal ligament fibroblasts. Head & Face Med. 2014;10(1).
16. Gaur S, Agnihotri R. Health effects of trace metals in electronic cigarette aerosols—a systematic review. Biol Trace Elem Res. 2019;188(2):295–315.
17. Azevedo A, Lobo I, Selores M. Allergic contact dermatitis and electronic cigarettes: Is nickel to blame? Contact Dermatitis. 2019. [Epub ahead of print]
18. Hickey S, Goverman J, Friedstat J, Sheridan R, Schulz J. Thermal injuries from exploding electronic cigarettes. Burns. 2018;44(5):1294–301.
19. U.S Food and Drug Administration. (2019). FDA. https://www.govinfo.gov/content/pkg/FR-2016-05-10/pdf/2016-10685.pdf. Accessed February 19, 2019.
20. Lallier TE, Moylan JT, Maturin E. Greater sensitivity of oral fibroblasts to smoked versus smokeless tobacco. J Periodontol. 2017;88(12):1356–65.
21. Javed F, Kellesarian S, Sundar I, Romanos G, Rahman I. Recent updates on electronic cigarette aerosol and inhaled nicotine effects on periodontal and pulmonary tissues. Oral Dis. 2017;23(8):1052–7.
22. Nguyen TT, Huynh, NNC, Seubbuk S, Nilmoje T, Wanasuntronwong A, Surarit R. Oxidative stress induced by Porphyromonas gingivalis lysate and nicotine in human periodontal ligament fibroblasts. Odontology. 2018. [Epub ahead of print]
23. Rouabhia M, Park HJ, Semlali A, Zakrzewski A, Chmielewski W, Chakir J. E-cigarette vapor induces an apoptotic response in human gingival epithelial cells through the caspase-3 pathway. J Cell Physiol. 2016;232(6):1539–47.
24. Scott A, Lugg ST, Aldridge K, Lewis KE, Bowden A, Mahida RY, et al. Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages. Thorax. 2018;73(12):1161–9.
25. Leite FR, Nascimento GG, Scheutz F, López R. Effect of smoking on periodontitis: a systematic review and meta-regression. Am J Prev Med. 2018;54(6):831–41.
Joan Pellegrini, PhD, RDH, is an associate professor in the Department of General Practice, Dental Hygiene Program at the VCU School of Dentistry. She is also a clinical researcher involved in multidisciplinary health-care research projects at the university. Pellegrini’s areas of interest include motivation and communication for health-care professionals, adult learning strategies and practice, preventive oral health strategies, multicultural diversity in health care, and evidence-based practice.
Denise Thieleman is finishing up her bachelor of science in dental hygiene at Virginia Commonwealth University, anticipated graduation date of May 2020. She holds a bachelor of science with a major in biology and minor in chemistry, also obtained from Virginia Commonwealth University. She was a certified dental assistant and scientist prior to beginning her career as a dental hygienist. For more information, email her at [email protected].
Christina Tulloch is in her final year of Virginia Commonwealth University’s bachelor of science in dental hygiene program. She holds a bachelor of science in biology with a minor in chemistry, and has more than eight years of prior experience as a dental assistant. For more information, email her at [email protected] or visit www.christinaintheloupe.weebly.com/.
