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Letters Recommending e-cigarettes

Safety of e-cigarettes still needs to be proved

BMJ 2014; 349 doi: (Published 15 July 2014) Cite this as: BMJ 2014;349:g4597

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We were dismayed by the approach of Valentine and Nicholson to the issue of e-cigarettes [1]. Of course, unexpected health consequences may occur in the medical profession as it has been also the case with several medications, such as thalidomide, cerivastatin and rofecoxib to name a few. But this cannot be used as a valid argument to oppose e-cigarettes. They suggest e-cigarettes should be quarantined until results from long-term studies are available, while in reality this is not a requirement for any other product approved for human consumption. Even for medications, no regulatory agency is asking for long-term safety data before being approved for use. Although some problems have emerged, such as the recent story with olmesartan [2], this cannot justify a request to provide long-term studies before approval of medications; it will just be impossible for anyone to cope with the financial cost, while at the same time evolution of new medications will become very slow.

We agree with Valentine and Nicholson that children are frequently exposed to products they find in their homes. That is why household and personal care products, together with medications, are the leading causes of poisonings in children [3]. Until now, there are no documented cases of deaths from exposure to e-cigarette liquids. It is misleading to quote occasional cases of accidental poisoning without providing professional medical reporting. The number of cases is extremely small compared with, for example, household cleaning products. Childproof caps have been now introduced by most producers/distributors and this alone will prevent these rare accidents. Of course, regulation should implement such a requirement. In any case, there has never been proposed that medications or household cleaning products should be banned because of poisonings, nor should this be a reason to restrict the size of packaging of these products. Moreover, it is time to re-evaluate the lethal dose of nicotine, which has historically being set at 40-60mg; this was the result of dubious self-experiments in the 19th century, with a recent review setting the lethal dose at 500-1000mg [4]. Of note, this dose does not take into consideration that voluminous vomiting is the first and most prominent symptom of nicotine ingestion. There are reports of ingesting 1500mg nicotine, with the patient being discharged from the hospital after few hours of observation without any adverse health consequences [5].

Valentine and Nicholson cite a review by Warren and Singh about the effects of nicotine in promoting cancer [6]. This as well as another review by Grando [7] referred to laboratory evidence, while there is no clinical study which has verified such findings. On the contrary, there is a wealth of epidemiological data of long-term nicotine intake from snus use. Evidence shows that there is minimal, if any, effect of snus (and the resulting nicotine intake) in cancer incidence [8,9]. In any case, even if a small residual risk remains, it is by far lower compared to the risk of continuing smoking, and is most probably not attributed to the nicotine content in snus. The extensive clinical evidence about snus use clearly supports the important role of tobacco harm reduction products in reducing smoking-related morbidity and mortality.

Evidence that inhalation of e-cigarette aerosols may be of concern for the lung is non-existent. Rather, the opposite may be true. There is now evidence from clinical studies [10] and research surveys [11] that smokers with asthma and COPD who switched to regular e-cigarette use benefitted substantially, with improvements in their respiratory symptoms and lung function. Although prospective studies are needed to better define the harm reversal potential of e-cigarettes in patients with already-established lung disease, the available evidence is important because asthma and COPD patients are particularly vulnerable to respiratory irritants and the e-cigarette aerosol does not set off respiratory exacerbations.

A point that has rarely being raised is that, unlike tobacco cigarettes which were developed and marketed for a non-smoker to become a smoker, e-cigarettes are developed and have been endorsed by some scientists strictly as a substitute, for smokers to become e-cigarette users. Thus, it is inappropriate to consider them as a new threat for public health, since they are not promoted as a new habit for everyone (i.e. non-smokers) to adopt. There is currently minimal adoption of e-cigarette use by non-smokers and youth (only 0.5% of non-smoking adolescents has used e-cigarettes in the past 30 days according to the Centers for Disease Control survey [12], while similar observations were reported in a survey of Korean adolescents [13]). Besides the recent estimation of the much-reduced risk of e-cigs compared to combustible nicotine containing products [14], there is also overwhelming evidence that e-cigarettes are by far less harmful compared to tobacco cigarettes [15]. What remains is to objectively quantify the exact reduction in risk; this will be evaluated through long-term studies. However, it is irresponsible to promote risks that are not proven and to deprive smokers of a product which, based on all scientific evidence, is reducing their exposure to health hazards to a large extent.

1. Valentine C, Nicholson P. Safety of e-cigarettes still needs to be proved. BMJ 2014;349:g4597.
2. Graham DJ, Zhou EH, McKean S, Levenson M, Calia K, Gelperin K, et al. Cardiovascular and mortality risk in elderly Medicare beneficiaries treated with olmesartan versus other angiotensin receptor blockers. Pharmacoepidemiol Drug Saf 2014;23:331-339.
3. Swedish Poisons Information Center. Annual Report 2013. Available at: (accessed on July 16, 2014).
4. Mayer B. How much nicotine kills a human? Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century. Arch Toxicol. 2014;88:5-7.
5. Christensen LB, van't Veen T, Bang J. Three cases of attempted suicide by ingestion of nicotine liquid used in e-cigarettes, Clinical Toxicology 2013;51:290.
6. Warren GW1, Singh AK. Nicotine and lung cancer. J Carcinog 2013;12:1.
7. Grando SA. Connections of nicotine to cancer. Nat Rev Cancer 2014;14:419-429.
8. Lee PN. The effect on health of switching from cigarettes to snus - a review. Regul Toxicol Pharmacol 2013;66:1-5.
9. Rodu B, Cole P. Lung cancer mortality: comparing Sweden with other countries in the European Union. Scand J Public Health 2009;37:481-486.
10. Polosa R, Morjaria J, Caponnetto P, Caruso M, Strano S, Battaglia E, et al. Effect of smoking abstinence and reduction in asthmatic smokers switching to electronic cigarettes: evidence for harm reversal. Int J Environ Res Public Health 2014;11:4965-4977.
11. Farsalinos KE, Romagna G, Tsiapras D, Kyrzopoulos S, Voudris V. Characteristics, perceived side effects and benefits of electronic cigarette use: a worldwide survey of more than 19,000 consumers. Int J Environ Res Public Health 2014;11:4356-4373.
12. Centers for Disease Control and Prevention (CDC). Notes from the field: Electronic cigarette use among middle and high school students—United States, 2011–2012. MMWR Morb Mortal Wkly Rep 2013;62:729–730.
13. Lee S, Grana RA, Glantz SA. Electronic cigarette use among Korean adolescents: a cross-sectional study of market penetration, dual use, and relationship to quit attempts and former smoking. J Adolesc Health 2014;54:684-690.
14. Nutt DJ, Phillips LD, Balfour D, Curran HV, Dockrell M, Foulds J, et al. Estimating the Harms of Nicotine-Containing Products Using the MCDA Approach. Eur Addict Res 2014;20:218-225.
15. Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Safety 2014;5:67-86.

Competing interests: Some studies performed by KF were carried out using funds provided to his institution (Onassis Cardiac Surgery Center) by e-cigarette companies. RP has received lecture fees and research funding from GlaxoSmithKline and Pfizer, manufacturers of stop smoking medications. He has also served as a consultant for Pfizer and Arbi Group Srl (Milano, Italy), the distributor of Categoria™ e-Cigarettes. R.P.’s research on electronic cigarettes is currently supported by LIAF (Lega Italiana AntiFumo).

16 July 2014
Konstantinos E. Farsalinos
Riccardo Polosa
Onassis Cardiac Surgery Center
Syggrou 356, Kallithea 17674, Greece