Intended for healthcare professionals

Rapid response to:


Evidence about electronic cigarettes: a foundation built on rock or sand?

BMJ 2015; 351 doi: (Published 15 September 2015) Cite this as: BMJ 2015;351:h4863

Rapid Response:

Response to McKee and Capewell

Below is a response to the central assertions of McKee and Capewell's analysis [1] of Public Health England's (PHE) report [2] on e-cigarettes (EC).

1. McKee and Capewell: “ …reduced smoking (as opposed to quitting) may not reduce overall risk of death [3].”

RESPONSE: Meta-analyses and a systematic review show that reduced smoking improves outcomes [4,5].
Moreover, McKee and Capewell’s citation [3] derives from cohorts showing similar toxicant exposure among reducers and non-reducers, indicating compensatory inhalation [6]. This would be expected without an alternate nicotine source. Conversely, dual users supplement their nicotine intake and should reduce their toxicant exposure per cigarette [7-9].
Indeed, EC interventions precede decreased CO and acrolein exposure among continuing smokers [10-13]. Additionally, dual use has already been shown to improve lung function [14,15] and pulmonary health [15,16].
While one cross-sectional study showed no reduced exposure among dual users [17], it measured only for weekly EC use (L Shahab, Personal communication). Furthermore, it cannot exclude longitudinal reductions.

2. McKee and Capewell: “The expression 'dual use'… rarely occurs in the PHE report”.

RESPONSE: Searching the report for the precise term “dual use” fails to uncover an entire section titled “Use of e-cigarettes while smoking” (cf. [18]).

3. McKee and Capewell: "Two thirds of EC users also smoke."

RESPONSE: Definitions are crucial: Smokers who occasionally vape and vapers who occasionally smoke are all ‘dual users’, yet their health risks are disparate. Most daily EC users don’t smoke regularly [19,20].

4. McKee and Capewell: “Dual use among daily 'vapers' apparently remained above 80% after 12 months follow-up.“

RESPONSE: PHE's report addresses this study, explaining that since only EC users who have failed to quit cigarettes were recruited, efficacy is invariably underestimated. Nevertheless, dedicated EC use while smoking strongly predicts future cessation [21,22].
Multi-year cohorts and randomized trials show that using nicotine replacements, smokeless tobacco or cessation drugs together with smoking increases future smoking cessation [23-29]. It is inconceivable that ECs promote the opposite.

5. McKee and Capewell: “The recent Cochrane review… concluded that the evidence was of 'low or very low quality by GRADE standards'.”

RESPONSE: The 'low' rating (downgraded from ‘moderate’) stems from the finding that the device in one trial delivers nicotine poorly, meaning effectiveness is underestimated. The 'very low' grade relates to the randomization against NRT, not absolute efficacy.
Furthermore, the GRADE ratings are relevant only to clinical trial results, but the Cochrane Review presents many other cogent lines of evidence [30].
Additionally, PHE’s conclusion that “recent studies support the Cochrane Review findings“ is entirely ignored.

6. McKee and Capewell: “The PHE report authors concede the weakness of the evidence, noting how a single observational study with substantial limitations offers 'some of the best evidence to date on the effectiveness of EC for use in quit attempts.'”

RESPONSE: These “substantial limitations” – namely, being “unable to explore prospective predictors of quitting, including pre-quit nicotine dependence” [2] – would, if anything, bias against a positive outcome (smokers switching to EC evidently being more dependent than those confident abstaining entirely). Though, the study went beyond adjustments typically undertaken, including controlling for pre-quit dependence indirectly [31].

7. McKee and Capewell: “… a recent systematic review, which the PHE report surprisingly fails to cite, came to a different conclusion.”

RESPONSE: The mentioned review largely neglects comparing toxicant levels to tobacco smoke, or even to consider the clinical significance of findings [32], while ignoring important systematic reviews which have successfully done so [33-35].
Moreover, its misrepresentation of almost every major issue in EC toxicology include the statements:
I. “Some studies found high maximum concentrations of total TSNA”, citing studies showing TSNAs 200-1,800 times below cigarette smoke levels [36-38].
II. “Exposure to formaldehyde was comparable with smoking", referring to a study calculating formaldehyde levels nine times below that from tobacco smoke [36].
III. “Propylene glycol has been found to exacerbate and/or induce multiple allergic symptoms in children”, citing a study stating that "apparently… outcomes were not driven by propylene glycol” [39].
IV. “Values below the threshold limit don't necessarily protect against the health effect of 200–300 daily inhalations over decades”, referring to safety limits calculated for 8 hours exposures “day after day, over a working lifetime” [40].
V. “These metals appear on the U.S. Food and Drug Administration's 'Harmful and Potentially Harmful Chemicals' list”, referring to metals detected below levels acceptable to the FDA for chronic inhalation [7,41-43].

8. McKee and Capewell attack the 95% estimate for "coming from" an analysis they dismiss on basis of limitations and conflicts of interests.

RESPONSE: This is surprising considering that PHE’s report independently assesses the toxicology, concluding that the figure "appears to remain a reasonable estimate" [2].

9. McKee and Capewell: “The authors categorically dismiss the possibility that e-cigarettes may be a gateway to smoking.”

RESPONSE: They do not [2]. They explain that gateway terminology is “poorly defined”, suggesting its use be contingent upon a framework of how the theory can be tested. Tentative evidence that ECs divert youth away from smoking was also noted.
McKee and Capewell’s alleged “emerging evidence” for the gateway hypothesis uses methodology invalidated in PHE’s report.

10. McKee and Capewell: “The PHE report seems to equate lack of evidence with evidence of lack of effect. It claims that there is 'no identified risk to bystanders,' a view that may be premature.”

RESPONSE: Reporting "no identified risk" never precludes hypothetical discoveries. However, the report shows that continuous passive exposure levels are 1,000 times below active levels, the latter being below levels known to cause harm [44].
Exaggerating the harms of passive vaping likely damages public health, as outlined elsewhere [45].

11. McKee and Capewell: “… a consensus may be emerging: the English chief medical officer recently said that if EC have a role in smoking cessation that should be as 'licensed medicines.'”

RESPONSE: In reality, a wide range of experts contend that such policies may protect cigarette sales, as outlined in PHE's report [7,46-51].

[1] McKee M, Capewell S. Evidence about electronic cigarettes: a foundation built on rock or sand?. BMJ 2015;:h4863. doi:10.1136/bmj.h4863
[2] McNeill A, Brose LS, Calder R, et al. E-cigarettes: an evidence update: a report commissioned by Public Health England. Public Health England, 2015
[3] Godtfredsen NS, Holst C, Prescott E, et al. Smoking reduction, smoking cessation, and mortality: a 16-year follow-up of 19,732 men and women from the Copenhagen Centre for Prospective Population Studies. Am J Epidemiol 2002;156:994-1001.
[4] Pisinger C, Godtfredsen N. Is there a health benefit of reduced tobacco consumption? A systematic review. Nicotine & Tobacco Res 2007;9:631-646. doi:10.1080/14622200701365327
[5] Lee PN. The effect of reducing the number of cigarettes smoked on risk of lung cancer, COPD, cardiovascular disease and FEV(1)--a review. Regul Toxicol Pharmacol 2013;67:372-81. doi:10.1016/j.yrtph.2013.08.016
[6] Godtfredsen N, Prescott E, Vestbo J et al. Smoking reduction and biomarkers in two longitudinal studies. Addiction 2006;101:1516-1522. doi:10.1111/j.1360-0443.2006.01542.x
[7] Abrams D, Axéll T, Bartsch P, et al. Comment on a letter urging WHO to treat electronic cigarettes as tobacco products or medicines: the importance of dispassionate presentation and interpretation of evidence. Nicotine Science and Policy, 26 Jun, 2014.
[8] Farsalinos K, LeHouezec J. Regulation in the face of uncertainty: the evidence on electronic nicotine delivery systems (e-cigarettes). RMHP 2015;:157. doi:10.2147/rmhp.s62116
[9] Brose L, Hitchman S, Brown J et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction 2015;110:1160-1168. doi:10.1111/add.12917
[10] Polosa R, Morjaria J, Caponnetto P et al. Effectiveness and tolerability of electronic cigarette in real-life: a 24-month prospective observational study. Intern Emerg Med 2013;9:537-546. doi:10.1007/s11739-013-0977-z
[11] Polosa R, Caponnetto P, Maglia M et al. Success rates with nicotine personal vaporizers: a prospective 6-month pilot study of smokers not intending to quit. BMC Public Health 2014;14:1159. doi:10.1186/1471-2458-14-1159
[12] Caponnetto P, Auditore R, Russo C et al. Impact of an Electronic Cigarette on Smoking Reduction and Cessation in Schizophrenic Smokers: A Prospective 12-Month Pilot Study. International Journal of Environmental Research and Public Health 2013;10:446-461. doi:10.3390/ijerph10020446
[13] McRobbie H, Phillips A, Goniewicz M et al. Effects of Switching to Electronic Cigarettes with and without Concurrent Smoking on Exposure to Nicotine, Carbon Monoxide, and Acrolein. Cancer Prevention Research 2015;8:873-878. doi:10.1158/1940-6207.capr-15-0058
[14] Polosa R, Morjaria J, Caponnetto P et al. Effect of Smoking Abstinence and Reduction in Asthmatic Smokers Switching to Electronic Cigarettes: Evidence for Harm Reversal. International Journal of Environmental Research and Public Health 2014;11:4965-4977. doi:10.3390/ijerph110504965
[15] Washington-Krauth S, Burns T, Walters R. Changes in lung function over time after initiation of E-cigarette use. Abstract presented at the 21st annual meeting of the Society for Research on Nicotine and Tobacco, Philadelphia, PA. 2015.
[16] Farsalinos K, Romagna G, Tsiapras D et al. Characteristics, Perceived Side Effects and Benefits of Electronic Cigarette Use: A Worldwide Survey of More than 19,000 Consumers. International Journal of Environmental Research and Public Health 2014;11:4356-4373. doi:10.3390/ijerph110404356
[17] Shahab L, Goniewicz M, Alwis U et al. Exposure to selected toxicants and carcinogens as a function of smoking status and long-term use of nicotine replacement therapy or electronic cigarettes. Abstract presented at the 21st annual meeting of the Society for Research on Nicotine and Tobacco, Philadelphia, PA. 2015.
[18] McKee M, Capewell S. Re: Evidence about electronic cigarettes: a foundation built on rock or sand?. 2015. (accessed 1 Dec 2015).
[19] Amato M, Boyle R, Levy D. How to define e-cigarette prevalence? Finding clues in the use frequency distribution. Tobacco Control Published Online First: 2015. doi:10.1136/tobaccocontrol-2015-052236
[20] Action on Smoking and Health. Use of electronic cigarettes (vapourisers) among adults in Great Britain. 2015 . (accessed 1 Dec 2015).
[21] Etter J, Bullen C. A longitudinal study of electronic cigarette users. Addictive Behaviors 2014;39:491-494. doi:10.1016/j.addbeh.2013.10.028
[22] Biener L, Hargraves J. A Longitudinal Study of Electronic Cigarette Use Among a Population-Based Sample of Adult Smokers: Association With Smoking Cessation and Motivation to Quit. Nicotine & Tobacco Research 2014;17:127-133. doi:10.1093/ntr/ntu200
[23] National Institute for Health and Care Excellence. Tobacco-Harm Reduction Approaches to Smoking: Guidance. London, UK: National Institute for Health and Care Excellence; 2013. Available from:
[24] Klemperer E, Hughes J. Does the Magnitude of Reduction in Cigarettes Per Day Predict Smoking Cessation? A Qualitative Review. Nicotine & Tobacco Research Published Online First: 2015. doi:10.1093/ntr/ntv058
[25] Wu L, Sun S, He Y et al. Effect of Smoking Reduction Therapy on Smoking Cessation for Smokers without an Intention to Quit: An Updated Systematic Review and Meta-Analysis of Randomized Controlled. International Journal of Environmental Research and Public Health 2015;12:10235-10253. doi:10.3390/ijerph120910235
[26] Asfar T, Ebbert J, Klesges R et al. Do smoking reduction interventions promote cessation in smokers not ready to quit?. Addictive Behaviors 2011;36:764-768. doi:10.1016/j.addbeh.2011.02.003
[27] Frost-Pineda K, Appleton S, Fisher M et al. Does Dual Use Jeopardize the Potential Role of Smokeless Tobacco in Harm Reduction?. Nicotine & Tobacco Research 2010;12:1055-1067. doi:10.1093/ntr/ntq147
[28] Rodu B. Dual Use. Nicotine & Tobacco Research 2011;13:221-221. doi:10.1093/ntr/ntq234
[29] Lee P. Health risks related to dual use of cigarettes and snus – A systematic review. Regulatory Toxicology and Pharmacology 2014;69:125-134. doi:10.1016/j.yrtph.2013.10.007
[30] McRobbie H, Bullen C, Hartmann-Boyce J et al. Electronic cigarettes for smoking cessation and reduction. Cochrane Database of Systematic Reviews Published Online First: 1996. doi:10.1002/14651858.cd010216.pub2
[31] Brown J, Beard E, Kotz D et al. Real-world effectiveness of e-cigarettes when used to aid smoking cessation: a cross-sectional population study. Addiction 2014;109:1531-1540. doi:10.1111/add.12623
[32] Pisinger C, Døssing M. A systematic review of health effects of electronic cigarettes. Prev Med 2014;69:248-260. doi:10.1016/j.ypmed.2014.10.009
[33] Burstyn I. Peering through the mist: systematic review of what the chemistry of contaminants in electronic cigarettes tells us about health risks. BMC Public Health 2014;14:18. doi:10.1186/1471-2458-14-18
[34] Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014;5:67-86. doi:10.1177/2042098614524430
[35] Hajek P, Etter JF, Benowitz N et al. Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit. Addiction 2014;109:1801-1810. doi:10.1111/add.12659
[36] Goniewicz ML, Knysak J, Gawron M et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control 2014;23:133-139. doi:10.1136/tobaccocontrol-2012-050859
[37] Kim HJ, Shin HS. Determination of tobacco-specific nitrosamines in replacement liquids of electronic cigarettes by liquid chromatography-tandem mass spectrometry. J Chromatogr A 2013;1291:48-55. doi:10.1016/j.chroma.2013.03.035
[38] Farsalinos KE, Romagna G, Voudris V. Authors miss the opportunity to discuss important public health implications. J Chromatogr A 2013;1312:155-156. doi:10.1016/j.chroma.2013.07.115
[39] Choi H, Schmidbauer N, Sundell J et al. Common Household Chemicals and the Allergy Risks in Pre-School Age Children. PLoS ONE 2010;5:e13423. doi:10.1371/journal.pone.0013423
[40] ACGIH. Chemical Substances Introduction. 2015. (accessed 3 Dec 2015).
[41] Siegel M. Metals in Electronic Cigarette Vapor are Below USP Standards for Metals in Inhalation Medications. The Rest of the Story: Tobacco News Analysis and Commentary. 2013. (accessed 5 Dec 2015).
[42] Farsalinos K. Metals and nanoparticles in e-cigarettes. 2013. (accessed 5 Dec 2015).
[43] Farsalinos K, Voudris V, Poulas K. Are Metals Emitted from Electronic Cigarettes a Reason for Health Concern? A Risk-Assessment Analysis of Currently Available Literature. International Journal of Environmental Research and Public Health 2015;12:5215-5232. doi:10.3390/ijerph120505215
[44] McNeill A, Hajek P. Underpinning evidence for the estimate that e-cigarette use is around 95% safer than smoking: authors’ note. Public Health England 2015. https://www. attachment_data/file/456704/McNeill-Hajek_ report_authors_note_on_evidence_for_95_ estimate.pdf (accessed 15 Dec 2015).
[45] Bates C. Wales vaping ban: silver lining may be larger than cloud. The counterfactual 2015. (accessed 20 Dec 2015).
[46] Bates C. 10 reasons not to regulate e-cigarettes as medicines. The counterfactual 2013. (accessed 15 Dec 2015).
[47] Hajek P, Foulds J, Houezec J et al. Should e-cigarettes be regulated as a medicinal device?. The Lancet Respiratory Medicine 2013;1:429-431. doi:10.1016/s2213-2600(13)70124-3
[48] Hajek P, Etter J, Benowitz N et al. Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit. Addiction 2014;109:1801-1810. doi:10.1111/add.12659
[49] Caponnetto P, Saitta D, Sweanor D et al. What to consider when regulating electronic cigarettes: Pros, cons and unintended consequences. International Journal of Drug Policy 2015;26:554-559. doi:10.1016/j.drugpo.2015.03.001
[50] Farsalinos K, LeHouezec J. Regulation in the face of uncertainty: the evidence on electronic nicotine delivery systems (e-cigarettes). RMHP 2015;:157. doi:10.2147/rmhp.s62116
[51] Saitta D, Ferro G, Polosa R. Achieving appropriate regulations for electronic cigarettes. Therapeutic Advances in Chronic Disease 2014;5:50-61. doi:10.1177/2040622314521271

Competing interests: No competing interests

09 February 2016
Zvi Herzig
Uvacharta Bachayim Institute
Jerusalem, Israel