The Laryngoscope C 2014 The American Laryngological, V
Rhinological and Otological Society, Inc.
Are E-Cigarettes Effective in Smoking Cessation? Andrew H. Y. Lee, BA; Brian J. Stater, MD; Lanny Close, MD; Rahmatullah Rahmati, MD BACKGROUND Electronic nicotine delivery systems (ENDS; commonly known as electronic cigarettes or e-cigarettes) have been commercially available in the United States since 2007, yet recently have generated substantial controversy as their use and availability expands. ENDS are battery-operated devices designed to resemble traditional cigarettes that heat and vaporize nicotinecontaining solutions. Each device contains a microelectrical circuit, activated by inhaling through a mouthpiece that vaporizes a propylene glycol–nicotine solution and delivers it to the user, an act often termed vaping.1–5 They are ubiquitously available commercially, sold from vendors ranging from the local corner gas station and drug store to the Internet marketplace. ENDS do not depend on combustion, meaning that the user and bystanders are theoretically not exposed to many of the harmful compounds and particulate matter produced by traditional cigarettes.5 Recently, there has been a drastic increase in usage and awareness of ENDS, largely as a result of shrewd, aggressive marketing.2 Although ENDS are marketed as a safer and healthier alternative to conventional cigarettes, much remains unknown. The longterm safety data on ENDS is scant and inconsistent, and there is a lack of internationally certified manufacturing sites.2 Whereas some public health officials have embraced ENDS as a potential pathway to smoking reduction or cessation, other experts are concerned that ENDS could undermine a decades-long public health campaign to denormalize and stigmatize smoking. These experts are concerned that ENDS could maintain nicotine addiction by deterring smokers from utilizing proven cessation tools, thus acting as a gateway to future smoking and increasing nicotine addiction among youth.5
From the Department of Otolaryngology–Head and Neck Surgery, Columbia University Medical Center, New York, New York, U.S.A. Editor’s Note: This Manuscript was accepted for publication September 2, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Rahmatullah Rahmati, MD, Department of Otolaryngology–Head and Neck Surgery, Columbia University Medical Center, 180 Fort Washington Avenue, HP 8-818, New York, NY 10032. E-mail: [email protected] DOI: 10.1002/lary.24954
Laryngoscope 125: April 2015
As physicians primarily involved in the treatment of head and neck malignancies, otolaryngologists have a particular responsibility in guiding patients toward effective methods of tobacco cessation. Furthermore, evidence-based recommendations on the efficacy of ENDS in smoking cessation will be paramount for sound policy development.
LITERATURE REVIEW Cigarette smoking represents the single most important cause of avoidable premature mortality in the world for both the smoker and for those exposed to cigarette smoke. Thus, tools that encourage abstinence or a reduction in smoking represent significant public health advancements. Although a number of available tobacco cessation aids are known to increase the likelihood of quitting smoking, they may lack efficacy in real-life settings. Because of this uncertainty, a number of ENDS users are attracted to e-cigarettes because they believe that they can help reduce or stop smoking. In an international study surveying current and former smokers in Canada, the United States, the United Kingdom, and Australia, the majority of smokers indicated that they used ENDS to reduce the usage (75%) or harm (80%) of traditional cigarettes or to help quit smoking them (85%).1 Whereas nonlongitudinal studies and anecdotal evidence tout the benefits of ENDS, longitudinal studies examining this question have produced less than convincing results (Table I). Indeed, in a longitudinal analysis in the same group of survey respondents, quitting did not differ between ENDS users and nonusers over a 1-year period.1 Recently, Bullen et al. conducted a randomized control trial with 657 participants that compared the effectiveness of ENDS versus nicotine patches in smoking cessation.2 After 6 months of follow-up, the authors were unable to demonstrate a statistically significant superiority of ENDS (7.3% abstinence at 6 months) compared to nicotine patches (5.8% abstinence) for smoking cessation. They concluded that, “Among smokers wanting to quit, nicotine e-cigarettes might be as effective as patches for achieving cessation at 6 months.” Moreover, the authors note that whereas e-cigarettes did not demonstrate superiority over patches in smoking cessation or reduction, they were also no more likely to lead to adverse events.2 Lee et al.: Electronic Cigarettes for Smoking Cessation
785
786
Wide variation in quality of studies, reflecting current state of ENDS literature Successful quitting not associated with ENDS use. 49 studies included, 14 of which address smoking cessation
Various; most studies conducted in US (23), Italy (5), UK (4), or multiple countries (7) Systematic Review 2013
Self-reported survey; low no. of ENDS users (88/949) possibly limiting statistical power ENDS use did not significantly predict quitting 1 year later. US smokers recruited from Knowledge Networks Web panel 949 Longitudinal survey over 12 months 2014
No non-ENDS control group; 39% lost to follow-up; discontinued model of ENDS used in study Reduction in smoking vs. baseline in all groups, but no significant differences between groups. Italian smokers with no intention to quit; randomized to ENDS with 0-mg (control), 7.2-mg, or 7.2-mg nicotine 36 weeks, then 5.4 mg 300 Randomized controlled trial over 12 months 2013 Caponnetto et al.3
Underpowered to detect significance due to lower than expected abstinence rates ENDS are no more effective than nicotine patches for smoking cessation. New Zealand smokers wanting to quit; randomized to nicotine e-cigarettes, nicotine patch (control), placebo e-cigarette 657 Randomized controlled trial over 6 months 2013 Bullen et al.2
Self-reported survey. Study not primarily designed to capture effect on cessation. Canada, US, UK, and Australian current and former smokers 5939 Longitudinal survey over 12 months
BEST PRACTICE Although nonlongitudinal studies and anecdotal evidence may routinely tout the benefits of ENDS, longitudinal studies suggest ENDS to be no more effective than already existing smoking cessation products. Furthermore, the long-term safety profile of these products remains unknown. The dearth of high-quality randomized control trials directly comparing the efficacy of ENDS compared to traditional smoking cessation fails to match the rapidly growing awareness and use of ENDS in the public sphere.
Pepper et al.5
LEVEL OF EVIDENCE Grana et al.4
Adkinson et al.1
2013
ENDS users were no more likely to quit smoking.
Limitations Findings Population N Study Design Year Study Authors
TABLE I. Summary of References Cited.
Laryngoscope 125: April 2015
Additional randomized control trials have been conducted, although in restricted patient populations. Caponnetto et al. conducted a prospective randomized control study examining 300 smokers over a 1-year period.3 This study examined smokers with no intention to quit at both 12 and 52 weeks of follow-up and compared three groups, all using ENDS but at three different nicotine strengths (0 mg, 7.2 mg, 7.2 mg for 6 weeks, followed by 5.4 mg). There was a statistically significant decrease in both smoking and adverse events (e.g., cough, dry mouth, shortness of breath) from baseline in all study groups, with 10% of participants reducing cigarette consumption by at least 50%, and 8.7% of individuals completely abstaining from cigarettes after 1 year. This is in light of an average yearly cessation rate of 0.02% in the general population. However, there was no significant difference seen among study groups; in addition, there was a non-ENDS control arm, reducing the generalizability of these results.3 More recently, a longitudinal analysis of ENDS for smoking cessation was conducted by surveying current smokers over a 1-year period. Of the 949 participants who completed the study after 1 year, it was found that ENDS use did not significantly predict quitting during that time (odd ratio, 0.71 [95% confidence interval, 0.35– 1.46]; P 5 0.35), nor was it associated with a change in cigarette consumption. Rather, intention to quit and cigarettes smoked per day significantly predicted quit status. However, the authors do caution that the number of ENDS users in the study (n 5 88) was small; thus, it may have been underpowered to detect a significant relationship between ENDS and smoking cessation.4 With respect to nonlongitudinal studies such as surveys, focus groups, case studies, and interviews, a recent systematic review on ENDS was conducted by Pepper et al.5 that reviewed 49 studies, of which 14 addressed the question of smoking cessation. The authors note that successful quitting was not associated with ENDS use, although there do exist reports of smoking cessation or reduction. Because smoking reduction may merely indicate dual use of ENDS and regular cigarettes, the authors note that smoking reduction, unlike smoking cessation, may not actually represent a positive public health outcome.5
Longitudinal studies of ENDS in smoking cessation are based on level 1b evidence (individual randomized controlled trial) and 2b evidence (individual cohort Lee et al.: Electronic Cigarettes for Smoking Cessation
study). Nonlongitudinal studies are based on level 4 evidence (systematic review of levels 3 and 4 evidence).
BIBLIOGRAPHY 1. Adkison SE, O’Connor RJ, Bansal-Travers M, et al. Electronic nicotine delivery systems: international tobacco control four-country survey. Am J Prev Med 2013;44:207–215.
Laryngoscope 125: April 2015
2. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet 2013;382:1629–1637. 3. Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and safety of an electronic cigarette (ECLAT) as tobacco cigarettes substitute: a prospective 12month randomized control design study. PLoS One 2013;8:e66317. 4. Grana RA, Popova L, Ling PM. A longitudinal analysis of electronic cigarette use and smoking cessation. JAMA Intern Med 2014;174:812–813. 5. Pepper JK, Brewer NT. Electronic nicotine delivery system (electronic cigarette) awareness, use, reactions and beliefs: a systematic review. Tob Control 2014;23:375–384. doi: 10.1136/tobaccocontrol-2013-051122. Epub 2013.
Lee et al.: Electronic Cigarettes for Smoking Cessation
787
Rhinological and Otological Society, Inc.
Are E-Cigarettes Effective in Smoking Cessation? Andrew H. Y. Lee, BA; Brian J. Stater, MD; Lanny Close, MD; Rahmatullah Rahmati, MD BACKGROUND Electronic nicotine delivery systems (ENDS; commonly known as electronic cigarettes or e-cigarettes) have been commercially available in the United States since 2007, yet recently have generated substantial controversy as their use and availability expands. ENDS are battery-operated devices designed to resemble traditional cigarettes that heat and vaporize nicotinecontaining solutions. Each device contains a microelectrical circuit, activated by inhaling through a mouthpiece that vaporizes a propylene glycol–nicotine solution and delivers it to the user, an act often termed vaping.1–5 They are ubiquitously available commercially, sold from vendors ranging from the local corner gas station and drug store to the Internet marketplace. ENDS do not depend on combustion, meaning that the user and bystanders are theoretically not exposed to many of the harmful compounds and particulate matter produced by traditional cigarettes.5 Recently, there has been a drastic increase in usage and awareness of ENDS, largely as a result of shrewd, aggressive marketing.2 Although ENDS are marketed as a safer and healthier alternative to conventional cigarettes, much remains unknown. The longterm safety data on ENDS is scant and inconsistent, and there is a lack of internationally certified manufacturing sites.2 Whereas some public health officials have embraced ENDS as a potential pathway to smoking reduction or cessation, other experts are concerned that ENDS could undermine a decades-long public health campaign to denormalize and stigmatize smoking. These experts are concerned that ENDS could maintain nicotine addiction by deterring smokers from utilizing proven cessation tools, thus acting as a gateway to future smoking and increasing nicotine addiction among youth.5
From the Department of Otolaryngology–Head and Neck Surgery, Columbia University Medical Center, New York, New York, U.S.A. Editor’s Note: This Manuscript was accepted for publication September 2, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Rahmatullah Rahmati, MD, Department of Otolaryngology–Head and Neck Surgery, Columbia University Medical Center, 180 Fort Washington Avenue, HP 8-818, New York, NY 10032. E-mail: [email protected] DOI: 10.1002/lary.24954
Laryngoscope 125: April 2015
As physicians primarily involved in the treatment of head and neck malignancies, otolaryngologists have a particular responsibility in guiding patients toward effective methods of tobacco cessation. Furthermore, evidence-based recommendations on the efficacy of ENDS in smoking cessation will be paramount for sound policy development.
LITERATURE REVIEW Cigarette smoking represents the single most important cause of avoidable premature mortality in the world for both the smoker and for those exposed to cigarette smoke. Thus, tools that encourage abstinence or a reduction in smoking represent significant public health advancements. Although a number of available tobacco cessation aids are known to increase the likelihood of quitting smoking, they may lack efficacy in real-life settings. Because of this uncertainty, a number of ENDS users are attracted to e-cigarettes because they believe that they can help reduce or stop smoking. In an international study surveying current and former smokers in Canada, the United States, the United Kingdom, and Australia, the majority of smokers indicated that they used ENDS to reduce the usage (75%) or harm (80%) of traditional cigarettes or to help quit smoking them (85%).1 Whereas nonlongitudinal studies and anecdotal evidence tout the benefits of ENDS, longitudinal studies examining this question have produced less than convincing results (Table I). Indeed, in a longitudinal analysis in the same group of survey respondents, quitting did not differ between ENDS users and nonusers over a 1-year period.1 Recently, Bullen et al. conducted a randomized control trial with 657 participants that compared the effectiveness of ENDS versus nicotine patches in smoking cessation.2 After 6 months of follow-up, the authors were unable to demonstrate a statistically significant superiority of ENDS (7.3% abstinence at 6 months) compared to nicotine patches (5.8% abstinence) for smoking cessation. They concluded that, “Among smokers wanting to quit, nicotine e-cigarettes might be as effective as patches for achieving cessation at 6 months.” Moreover, the authors note that whereas e-cigarettes did not demonstrate superiority over patches in smoking cessation or reduction, they were also no more likely to lead to adverse events.2 Lee et al.: Electronic Cigarettes for Smoking Cessation
785
786
Wide variation in quality of studies, reflecting current state of ENDS literature Successful quitting not associated with ENDS use. 49 studies included, 14 of which address smoking cessation
Various; most studies conducted in US (23), Italy (5), UK (4), or multiple countries (7) Systematic Review 2013
Self-reported survey; low no. of ENDS users (88/949) possibly limiting statistical power ENDS use did not significantly predict quitting 1 year later. US smokers recruited from Knowledge Networks Web panel 949 Longitudinal survey over 12 months 2014
No non-ENDS control group; 39% lost to follow-up; discontinued model of ENDS used in study Reduction in smoking vs. baseline in all groups, but no significant differences between groups. Italian smokers with no intention to quit; randomized to ENDS with 0-mg (control), 7.2-mg, or 7.2-mg nicotine 36 weeks, then 5.4 mg 300 Randomized controlled trial over 12 months 2013 Caponnetto et al.3
Underpowered to detect significance due to lower than expected abstinence rates ENDS are no more effective than nicotine patches for smoking cessation. New Zealand smokers wanting to quit; randomized to nicotine e-cigarettes, nicotine patch (control), placebo e-cigarette 657 Randomized controlled trial over 6 months 2013 Bullen et al.2
Self-reported survey. Study not primarily designed to capture effect on cessation. Canada, US, UK, and Australian current and former smokers 5939 Longitudinal survey over 12 months
BEST PRACTICE Although nonlongitudinal studies and anecdotal evidence may routinely tout the benefits of ENDS, longitudinal studies suggest ENDS to be no more effective than already existing smoking cessation products. Furthermore, the long-term safety profile of these products remains unknown. The dearth of high-quality randomized control trials directly comparing the efficacy of ENDS compared to traditional smoking cessation fails to match the rapidly growing awareness and use of ENDS in the public sphere.
Pepper et al.5
LEVEL OF EVIDENCE Grana et al.4
Adkinson et al.1
2013
ENDS users were no more likely to quit smoking.
Limitations Findings Population N Study Design Year Study Authors
TABLE I. Summary of References Cited.
Laryngoscope 125: April 2015
Additional randomized control trials have been conducted, although in restricted patient populations. Caponnetto et al. conducted a prospective randomized control study examining 300 smokers over a 1-year period.3 This study examined smokers with no intention to quit at both 12 and 52 weeks of follow-up and compared three groups, all using ENDS but at three different nicotine strengths (0 mg, 7.2 mg, 7.2 mg for 6 weeks, followed by 5.4 mg). There was a statistically significant decrease in both smoking and adverse events (e.g., cough, dry mouth, shortness of breath) from baseline in all study groups, with 10% of participants reducing cigarette consumption by at least 50%, and 8.7% of individuals completely abstaining from cigarettes after 1 year. This is in light of an average yearly cessation rate of 0.02% in the general population. However, there was no significant difference seen among study groups; in addition, there was a non-ENDS control arm, reducing the generalizability of these results.3 More recently, a longitudinal analysis of ENDS for smoking cessation was conducted by surveying current smokers over a 1-year period. Of the 949 participants who completed the study after 1 year, it was found that ENDS use did not significantly predict quitting during that time (odd ratio, 0.71 [95% confidence interval, 0.35– 1.46]; P 5 0.35), nor was it associated with a change in cigarette consumption. Rather, intention to quit and cigarettes smoked per day significantly predicted quit status. However, the authors do caution that the number of ENDS users in the study (n 5 88) was small; thus, it may have been underpowered to detect a significant relationship between ENDS and smoking cessation.4 With respect to nonlongitudinal studies such as surveys, focus groups, case studies, and interviews, a recent systematic review on ENDS was conducted by Pepper et al.5 that reviewed 49 studies, of which 14 addressed the question of smoking cessation. The authors note that successful quitting was not associated with ENDS use, although there do exist reports of smoking cessation or reduction. Because smoking reduction may merely indicate dual use of ENDS and regular cigarettes, the authors note that smoking reduction, unlike smoking cessation, may not actually represent a positive public health outcome.5
Longitudinal studies of ENDS in smoking cessation are based on level 1b evidence (individual randomized controlled trial) and 2b evidence (individual cohort Lee et al.: Electronic Cigarettes for Smoking Cessation
study). Nonlongitudinal studies are based on level 4 evidence (systematic review of levels 3 and 4 evidence).
BIBLIOGRAPHY 1. Adkison SE, O’Connor RJ, Bansal-Travers M, et al. Electronic nicotine delivery systems: international tobacco control four-country survey. Am J Prev Med 2013;44:207–215.
Laryngoscope 125: April 2015
2. Bullen C, Howe C, Laugesen M, et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet 2013;382:1629–1637. 3. Caponnetto P, Campagna D, Cibella F, et al. EffiCiency and safety of an electronic cigarette (ECLAT) as tobacco cigarettes substitute: a prospective 12month randomized control design study. PLoS One 2013;8:e66317. 4. Grana RA, Popova L, Ling PM. A longitudinal analysis of electronic cigarette use and smoking cessation. JAMA Intern Med 2014;174:812–813. 5. Pepper JK, Brewer NT. Electronic nicotine delivery system (electronic cigarette) awareness, use, reactions and beliefs: a systematic review. Tob Control 2014;23:375–384. doi: 10.1136/tobaccocontrol-2013-051122. Epub 2013.
Lee et al.: Electronic Cigarettes for Smoking Cessation
787
