Friday, February 1, 2019

E-cigarettes to assist with smoking cessation

Excerpts from an editorial published January 30, 2019 (Belinda Borrelli and George T. O’Connor; DOI: 10.1056/NEJMe1816406)

·         The prevalence of tobacco smoking in the United States has declined to 14.0% but still exceeds 25% among high-risk subgroups (1,2).

·         Electronic cigarettes (e-cigarettes) are not approved by FDA for smoking cessation, but Americans trying to quit smoking use these products more frequently than FDA-approved cessation aids (3).

·         Hajek et al (4) now report in the NEJM the results of a multi-center, pragmatic, randomized trial of e-cigarettes, as compared with nicotine-replacement therapy, as a smoking-cessation treatment within the U.K. National Health Service smoking-cessation program. In addition to behavioral support, participants received either a second-generation refillable e-cigarette or a 3-month supply of whichever nicotine-replacement products they preferred. After 1 year, the rate of abstinence from smoking tobacco, validated by exhaled carbon monoxide concentration, was higher in the e-cigarette group (18.0%) than in the nicotine-replacement group (9.9%).

o   Trial limitations: possibility that smoking-cessation counsellors who were aware of the treatment assignments may have influenced patient expectations.

·         These findings must be considered in the context of FDA-approved medications for smoking cessation that have acceptable safety profiles.  Treatment with nicotine-replacement therapy and bupropion achieves abstinence rates of approximately 25 to 26% at 6 months and 20% at 1 year, (5) with slightly higher abstinence rates for combination therapy than for monotherapy (6). Varenicline has been shown to outperform bupropion, all forms of nicotine-replacement therapy, and placebo, with a 26% abstinence rate through 24 weeks of follow-up among participants without psychiatric diagnoses (7). The 1-year abstinence rate of 18% reported by Hajek et al. for the e-cigarette group is similar to these outcomes.

·         This evidence of effectiveness must be balanced against the short-term and long-term safety of e-cigarettes. The data from Hajek et al. are reassuring: the e-cigarette group had greater declines in the incidence of cough and phlegm than the nicotine-replacement group, no excess wheezing or dyspnea, and only a small incidence of oropharyngeal irritation. More frequent respiratory serious adverse events in the e-cigarette group than in the nicotine-replacement group (5 vs. 1) did not appear to be related to e-cigarette use.

·         Previous reports have suggested short-term clinical benefit among patients with these conditions who switch from tobacco smoking to e-cigarette use (8). 

·         The use of e-cigarettes by pregnant women, who were excluded from the trial by Hajek et al., raises special safety concerns.

·         Nicotine-patch use during pregnancy is associated with a higher rate of smoking cessation and better child-development outcomes than placebo, (9) there are no such reassuring data for e-cigarettes.

·         A key finding of Hajek et al. is that among participants with sustained abstinence at 1 year, 63 of 79 (80%) in the e-cigarette group were still using e-cigarettes, whereas only 4 of 44 (9%) in the nicotine-replacement group were still using nicotine replacement.

·         E-cigarette vapor contains many toxins and exerts potentially adverse biologic effects on human cells in vitro or in animal models, although toxin levels and biologic effects are generally lower than those of tobacco smoke (10). 

·         A study involving humans showed an altered bronchial epithelial proteome in association with e-cigarette use, including some protein alterations also seen among tobacco smokers (11). In a mouse model, inhalational exposure to nebulized e-cigarette liquid containing nicotine resulted in distal airspace enlargement that was consistent with pulmonary emphysema (12). These findings argue against complacency in accepting the transition from tobacco smoking to indefinite e-cigarette use as a completely successful smoking-cessation outcome.

·         An additional societal consideration is the effect of adult e-cigarette use on children and young adults.

·         There is substantial evidence that e-cigarette use by youth increases the risk of smoking combustible tobacco cigarettes, (10) and the U.S. Surgeon General has recently declared e-cigarette use among youth “an epidemic.” (13)

·         A consensus has emerged that e-cigarettes are safer than traditional combustible cigarettes, (10) but it remains controversial whether e-cigarettes should be recommended as a first-line treatment to assist smoking cessation, alongside FDA-approved treatments.

·         The appropriate duration of e-cigarette “treatment” for smokers trying to quit is also uncertain.

·         e-cigarettes be used only when FDA-approved treatments (combined with behavioral counseling) fail, that patients be advised to use the lowest dose needed to manage their cravings, and that there be a clear timeline and “off ramp” for use.

·         Use of e-cigarettes should be monitored by health care providers

·         The efficacy and safety of e-cigarettes need to be evaluated in high-risk subgroups

·         Further research on the health consequences of long-term e-cigarette use is needed.

(Source: This editorial was published on January 30, 2019, at


1.     Wang TW, Asman K, Gentzke AS, et al. Tobacco product use among adults — United States, 2017. MMWR Morb Mortal Wkly Rep. 2018;67:1225-1232.
2.     Borrelli B, Busch A, Dunsiger S. Cigarette smoking among adults with mobility impairments: a US population-based survey. Am J Public Health 2014;104:1943-9.
3.     Benmarhnia T, Pierce JP, Leas E, et al. Can e-cigarettes and pharmaceutical aids increase smoking cessation and reduce cigarette consumption? Findings from a nationally representative cohort of American smokers. Am J Epidemiol 2018;187:2397-2404.
4.     Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. DOI: 10.1056/NEJMoa1808779.
5.     Rosen LJ, Galili T, Kott J, et al. Diminishing benefit of smoking cessation medications during the first year: a meta-analysis of randomized controlled trials. Addiction 2018;113:805-16.
6.     Windle SB, Filion KB, Mancini JG, et al. Combination therapies for smoking cessation: a hierarchical Bayesian meta-analysis. Am J Prev Med 2016;51:1060-71.
7.     Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016;387:2507-20.
8.     Polosa R, Morjaria JB, Caponnetto P, et al. Evidence for harm reduction in COPD smokers who switch to electronic cigarettes. Respir Res 2016;17:166.
9.     Cooper S, Taggar J, Lewis S, et al. Effect of nicotine patches in pregnancy on infant and maternal outcomes at 2 years: follow-up from the randomised, double-blind, placebo-controlled SNAP trial. Lancet Respir Med 2014;2:728-37.
10.  Stratton K, Kwan LY, Eaton DL, eds. Public health consequences of e-cigarettes. Washington, DC: National Academies Press, January 2018.
11.  Ghosh A, Coakley RC, Mascenik T, et al. Chronic e-cigarette exposure alters the human bronchial epithelial proteome. Am J Respir Crit Care Med 2018;198:67-76.
12.  Garcia-Arcos I, Geraghty P, Baumlin N, et al. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax 2016;71:1119-29.
13.  Stein R. Surgeon General warns youth vaping is now an “epidemic.” NPR. December 18, 2018(

Dr KK Aggarwal
Padma Shri Awardee
President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)
Group Editor-in-Chief IJCP Publications
President Heart Care Foundation of India
Past National President IMA

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