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Point and Counterpoint |

POINT: Does the Risk of Electronic Cigarettes Exceed Potential Benefits? YesRisk of E-Cigs Higher Than Benefits? Yes FREE TO VIEW

Mark V. Avdalovic, MD, MAS; Susan Murin, MD, FCCP
Author and Funding Information

From the Division of Pulmonary, Critical Care and Sleep Medicine, UC Davis School of Medicine; and VA Northern California Health Care System.

CORRESPONDENCE TO: Mark Avdalovic, MD, MAS, Division of Pulmonary, Critical Care and Sleep Medicine, UC Davis School of Medicine, 4150 V St, PSSB 3400, Sacramento, CA 95817; e-mail: mark.avdalovic@ucdmc.ucdavis.edu


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(3):580-582. doi:10.1378/chest.15-0538
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Published online

The use of electronic cigarettes (e-cigarettes) continues to dramatically increase, and the debate over their safety and appropriate use has heated up in parallel. We as pulmonary clinicians are called upon to advise our patients and others about e-cigarettes, which presents challenges given the current limitations of the data upon which our advice should be based. What do we say?

At first glance, the use of e-cigarettes appears to be an attractive option. Evaluation of the ingredients and particulates associated with e-cigarette vapors has demonstrated a substantial decrease in carcinogens compared with the traditional cigarette.1 e-Cigarettes can deliver nicotine in a form that is familiar to the traditional smoker, yet lacks many of the harmful constituents of cigarette smoke. The optimist envisions a cohort of multi-pack-year smokers switching to the e-cigarette with a resultant rapid decrease in risks of heart disease, chronic lung disease, and cancer. But is this optimism justified by empirical evidence of safety and favorable data on patterns of use or is this simply wishful thinking?

Too often in the debate about the e-cigarette the focus is upon the relative lack of proof of harm and the flawed assumption that lack of evidence of harm equals evidence of safety. This is the wrong perspective. Instead, the focus needs to be upon proof that e-cigarettes are safe (alone or in conjunction with active smoking because many are dual users), are effective in accomplishing some good (smoking reduction or cessation), and do not promote an increase in the population of nicotine-addicted individuals. At present, we lack such proof.

Most defenders of e-cigarette use base their perspective on the concept of harm reduction, and the assumption that the only users of e-cigarettes are or will be current tobacco smokers looking for a safer cigarette. One of the early concerns with the e-cigarette, however, was that it might introduce young, non-tobacco users to nicotine addiction, and there is recent evidence to support the validity of that concern. A recent cross-sectional survey-based study reported on trends of e-cigarette use from 2010 through 2013.2 e-Cigarette use increased dramatically over this interval. The highest prevalence of use was among very young adults, 18 to 25 years of age. One-third of current e-cigarette users were nonsmokers, and 1.4% were never smokers.2 The trend toward younger groups being aware of and using e-cigarettes is also on the rise. A survey of 4,780 middle school and high school students from Connecticut identified a high rate of awareness, as well as current and lifetime use, of e-cigarettes among those students.3 Additionally, a study that sought to gauge “openness” to starting tobacco products identified the use of e-cigarettes as a significant factor in being likely to try tobacco products in the future.4 What all of these studies tell us collectively is that the cohort of e-cigarette users is growing, young, and open to using both e-cigarettes and traditional tobacco products: not a group of seasoned smokers trying to quit or looking for an alternative to the traditional cigarette. The e-cigarette may well contribute to an overall increase in nicotine addiction.

e-Cigarettes have not been marketed as cessation aids (as doing so would have implications for US Food and Drug Administration regulation) but have been advocated for this purpose, and many smokers have purchased these products as a way to stop smoking. Despite anecdotal reports that suggest effectiveness, there is not good evidence to suggest that e-cigarettes are superior to traditional, US Food and Drug Administration-approved approaches to smoking cessation. As an extension of their previous nonrandomized pilot study, Caponnetto et al5 conducted a clinical study of electronic nicotine delivery system devices in cigarette smokers not intending to quit. The investigators randomized 300 subjects to one of three arms, then followed subjects for eight visits over 52 weeks to assess for a ≥ 50% reduction in smoking, abstinence, and adverse events. The groups were as follows: (1) 12 weeks of 7.2-mg nicotine e-cigarettes; (2) 6 weeks of 7.2-mg nicotine, followed by 6 weeks of 5.4-mg nicotine, e-cigarettes; and (3) 12 weeks of placebo e-cigarettes which looked like the nicotine-containing e-cigarettes but contained only the carrier liquid. Under the intention-to-treat analysis, there were no significant differences between the groups in terms of cessation rates or reduction in the number of cigarettes smoked at 52 weeks. Bullen et al6 conducted a pragmatic randomized controlled trial to assess the efficacy of e-cigarettes for smoking cessation compared with nicotine replacement therapy. Six hundred fifty-seven smokers desiring to quit were randomized to receive 16-mg e-cigarettes, 21-mg nicotine patches daily, or placebo e-cigarettes in a 4:4:1 ratio. Though at 1 month there was a significant difference in continuous abstinence favoring e-cigarettes (relative risk, 1.46; 95% CI, 1.04-2.04), this difference did not persist at 3 and 6 months. Given inadequate safety data and other concerns, and the lack of evidence of superior efficacy, we would be remiss in recommending e-cigarettes over other approaches to smoking cessation.

Multiple studies have reported on the toxicities that are associated with e-cigarette use. These studies have established that e-cigarettes are associated with increased nausea, vomiting, headache, choking, and upper airway irritation.7 One study demonstrated that after only 5 min of smoking an e-cigarette subjects’ airway resistance significantly increased from baseline. In these same individuals, fraction of expired nitric oxide was also decreased, indicating that after only 5 min of exposure there was a significant change in the biologic function of the lung.8 Marini et al9 went on to show that the effects on nitric oxide synthesis by the lung were similar between e-cigarettes and traditional cigarettes. Using an animal model of asthma, researchers have established that e-cigarettes exacerbate the basic biology that drives asthmatic symptoms by increasing the influx of eosinophils into the airway and increasing synthesis of IL-4, IL-5, IL-13, and IgE.10 Perhaps most concerning is recent data that have established that e-cigarettes can alter gene expression in bronchial epithelial cells, leading to a higher malignant transformation, in a similar way to traditional cigarettes.11 The early evidence for the toxic effect of e-cigarettes is clear; they are an irritant to the airway, and they have direct effects on gene expression and protein synthesis that promote airway inflammation and potential malignant transformation.

There is no evidence that e-cigarettes are safe, and there is some evidence that they may in fact be harmful, both through introducing new young users to nicotine addiction and through direct effects upon the lung. It took decades for the medical community to recognize, prove, and accept that cigarettes are a major health hazard; we should not make the same error with e-cigarettes. We risk losing hard-won ground in the battle on smoking through the so-called “renormalization” of smoking that may attend the uncritical acceptance of e-cigarettes, and that is a stated goal of the e-cigarette industry.12 Additional research to fully understand the health effects of e-cigarettes, including among dual users of e-cigarettes and traditional cigarettes, is needed. Harm-reduction arguments are only valid if we can objectively document an overall reduction in harm, at both the individual and population levels, and at present we cannot. When patients come to us and ask for guidance about the use of e-cigarettes they are expecting a response informed by data. The limited data we have at present do not demonstrate benefits exceeding known risks.

e-cigarette

electronic cigarette

FDA

US Food and Drug Administration

NRT

nicotine replacement therapy

Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014;5(2):67-86. [CrossRef] [PubMed]
 
McMillen RC, Gottlieb MA, Whitmore Shaefer RM, Winickoff JP, Klein JD. Trends in electronic cigarette use among US adults: use is increasing in both smokers and nonsmokers [published online ahead of print November 6, 2014]. Nicotine Tob Res. doi:10.1093/ntr/ntu213.
 
Krishnan-Sarin S, Morean ME, Camenga DR, Cavallo DA, Kong G. E-cigarette use among high school and middle school adolescents in Connecticut. Nicotine Tob Res. 2015;17(7):810-818. [CrossRef] [PubMed]
 
Coleman BN, Apelberg BJ, Ambrose BK, et al. Association between electronic cigarette use and openness to cigarette smoking among US young adults. Nicotine Tob Res. 2015;17(2):212-218. [CrossRef] [PubMed]
 
Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS ONE. 2013;8(6):e66317. [CrossRef] [PubMed]
 
Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382(9905):1629-1637. [CrossRef] [PubMed]
 
Meo SA, Al Asiri SA. Effects of electronic cigarette smoking on human health. Eur Rev Med Pharmacol Sci. 2014;18(21):3315-3319. [PubMed]
 
Vardavas CI, Anagnostopoulos N, Kougias M, Evangelopoulou V, Connolly GN, Behrakis PK. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide. Chest. 2012;141(6):1400-1406. [CrossRef] [PubMed]
 
Marini S, Buonanno G, Stabile L, Ficco G. Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide. Toxicol Appl Pharmacol. 2014;278(1):9-15. [CrossRef] [PubMed]
 
Lim HB, Kim SH. Inhallation of e-cigarette cartridge solution aggravates allergen-induced airway inflammation and hyper-responsiveness in mice. Toxicol Res. 2014;30(1):13-18. [CrossRef] [PubMed]
 
Park SJ, Walser TC, Perdomo C, et al. The effect of e-cigarette exposure on airway epithelial cell gene expression and transformation [abstract B16]. Clin Cancer Res. 2014;20.
 
Fairchild AL, Bayer R, Colgrove J. The renormalization of smoking? E-cigarettes and the tobacco “endgame.” N Engl J Med. 2014;370(4):293-295. [CrossRef] [PubMed]
 

Figures

Tables

References

Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014;5(2):67-86. [CrossRef] [PubMed]
 
McMillen RC, Gottlieb MA, Whitmore Shaefer RM, Winickoff JP, Klein JD. Trends in electronic cigarette use among US adults: use is increasing in both smokers and nonsmokers [published online ahead of print November 6, 2014]. Nicotine Tob Res. doi:10.1093/ntr/ntu213.
 
Krishnan-Sarin S, Morean ME, Camenga DR, Cavallo DA, Kong G. E-cigarette use among high school and middle school adolescents in Connecticut. Nicotine Tob Res. 2015;17(7):810-818. [CrossRef] [PubMed]
 
Coleman BN, Apelberg BJ, Ambrose BK, et al. Association between electronic cigarette use and openness to cigarette smoking among US young adults. Nicotine Tob Res. 2015;17(2):212-218. [CrossRef] [PubMed]
 
Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS ONE. 2013;8(6):e66317. [CrossRef] [PubMed]
 
Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013;382(9905):1629-1637. [CrossRef] [PubMed]
 
Meo SA, Al Asiri SA. Effects of electronic cigarette smoking on human health. Eur Rev Med Pharmacol Sci. 2014;18(21):3315-3319. [PubMed]
 
Vardavas CI, Anagnostopoulos N, Kougias M, Evangelopoulou V, Connolly GN, Behrakis PK. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide. Chest. 2012;141(6):1400-1406. [CrossRef] [PubMed]
 
Marini S, Buonanno G, Stabile L, Ficco G. Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide. Toxicol Appl Pharmacol. 2014;278(1):9-15. [CrossRef] [PubMed]
 
Lim HB, Kim SH. Inhallation of e-cigarette cartridge solution aggravates allergen-induced airway inflammation and hyper-responsiveness in mice. Toxicol Res. 2014;30(1):13-18. [CrossRef] [PubMed]
 
Park SJ, Walser TC, Perdomo C, et al. The effect of e-cigarette exposure on airway epithelial cell gene expression and transformation [abstract B16]. Clin Cancer Res. 2014;20.
 
Fairchild AL, Bayer R, Colgrove J. The renormalization of smoking? E-cigarettes and the tobacco “endgame.” N Engl J Med. 2014;370(4):293-295. [CrossRef] [PubMed]
 
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