- E-cigarettes deliver nicotine in an aerosol for inhalation and simulate aspects of cigarette smoking; they do not burn tobacco.
- Randomised controlled trials suggest they are modestly effective at assisting smoking cessation and smoking reduction.
- Short-term use of e-cigarettes is far less harmful than tobacco smoking; the health effects of long-term use are as yet unknown.
- Concerns about widespread e-cigarette use — that it will renormalise smoking behaviour and act as a gateway to smoking — are not substantiated by current evidence.
- For smokers who have tried and failed to quit with standard therapies, e-cigarettes may be considered as an option, but the limits of current knowledge should be explained.
Supporting smokers to quit as soon as possible is one of the most urgent priorities in healthcare
. Tobacco smoking is the leading preventable cause of premature death worldwide: the World Health Organization (WHO) projects that there will be more than one billion deaths caused by tobacco consumption within the 21st century
. Smoking cessation is highly cost-effective and confers immediate health benefits for smokers. However, despite significant progress being made in tobacco control in many countries, a large proportion of people still smoke, and among those who have quit smoking, most relapse within a few weeks or months: indeed, achieving complete and sustained smoking abstinence seems unattainable for many people.
Usual care in smoking cessation treatment includes behavioural support and medications such as nicotine replacement therapies (NRT; nicotine patches, gum, inhalators, lozenges, nasal sprays), bupropion and varenicline. All are effective treatments, but long-term quit rates are low, with only around one in eight smokers who use them managing to quit for a year or more,
. Additional efficacious interventions are needed to assist these smokers.
The application of a harm reduction approach — one that is widely accepted and used in other fields, such as opiate addiction— may offer promise. Tobacco harm reduction provides people with the opportunity to reduce exposure to harmful inhaled tobacco smoke by substituting less harmful ways of consuming tobacco or nicotine,
. Nicotine is relatively non-toxic and is not itself the direct cause of any smoking-related illness,
. Rather, the key to tobacco harm reduction is eliminating the inhalation of the combustion products generated when tobacco is burned at high temperatures, as in cigarettes. It is these toxicants that are responsible for the majority of the serious health risks associated with smoking tobacco
However, many tobacco control advocates are rightly cautious of adopting a harm reduction approach in tobacco smoking. They cite the introduction of ‘light cigarettes’ by the tobacco industry several decades ago, which failed to deliver health benefits and merely made the industry appear responsive to public concerns. However, new potential reduced-harm products are entering the market that promise to minimise the harms of smoking tobacco while delivering equivalent satisfaction for smokers. One such class of product has emerged in the last decade that offers real potential to help many smokers reduce their risks from tobacco smoke exposure: electronic cigarettes, popularly known as ‘e-cigarettes’ (ECs), sometimes referred to by health authorities, or in the scientific literature, as electronic nicotine delivery systems (ENDS)
This article describes the ‘disruptive innovation’ of ECs, their potential in tobacco control and the challenges they present, while also offering advice for clinicians and considering future developments.
Sources and selection criteria
To identify scientific studies, searches were performed on Google Scholar and PubMed/MEDLINE using the search terms ‘e-cigarette’ or ‘electronic cigarette’ and ‘smoking cessation’ from 2004 to October 2015 inclusive. There were no exclusion criteria. Other articles, technical reports and documents cited in the reference lists of publications were identified and located on organisation websites (such as those of the Cochrane Library, WHO and Public Health England) via Google search or via Google Scholar.
Emergence of e-cigarettes
The first EC was invented in China in 2003 by pharmacist Hon Lik as a means to quit smoking. ECs are a diverse group of battery-operated inhalation devices capable of delivering nicotine in a cloud of aerosol generated by heating a liquid mixture of propylene glycol, vegetable glycerol, water, ethanol, flavourings and other additives that usually include nicotine. The aerosol is generated by a heating coil that is activated when suction is applied to the mouthpiece or a button is pressed by the user,
The EC user (known as a ‘vaper’) inhales and exhales the vapour
. The aerosol looks like tobacco smoke but, unlike cigarettes, it is not generated continuously and is only visible when the user exhales
ECs have evolved considerably from early devices. The first generation products were small cigarette lookalikes (‘cigalikes’) with low capacity batteries and a heating element surrounded by a liquid-soaked poly-foam (‘cartomiser’)
. Most cigalikes include an LED at the tip that lights up when suction is applied, but generally with a colour that distinguishes them from conventional cigarettes
. More recent second-generation and third-generation ECs do not resemble cigarettes in size or shape,
have higher-capacity batteries, larger atomisers, and a refillable (transparent) tank (‘clearomiser’), with electronic circuits that provide the ability to set the power delivery to the atomiser,
. The newer devices offer advantages to users over earlier ones because they generate a more consistent aerosol that contains greater nicotine concentration and provide users with the ability to modify different components of the device (i.e. the battery voltage or the wick used to absorb the liquid) and to alter the amount of nicotine in the aerosol.
Hundreds of different brands and models of ECs are available, along with thousands of different liquid formulations sold in cartridges or in small refill bottles. In a US study conducted in January 2014, Zhu et al. found 466 brands of devices and 7,764 unique flavours advertised on the internet
. These include tobacco-like flavours as well as those advertised as having the characteristics of fruits, sweets, drinks (coffee, alcoholic beverages), and many others,
. EC brands also differ in nicotine delivery and the accuracy of labelling of nicotine content may vary by manufacturer (resulting in variations of 0Âµg to 35Âµg per puff),
. Finally, a growing number of vapers are sourcing individual ingredients (e.g. nicotine, vegetable glycerol, flavourings, etc.) to mix their own strength and flavour of liquid
The EC market has grown dramatically over the past few years. There are now millions of users worldwide, with sales of billions of dollars. Vapour retail sales are expected to reach US$3.5bn in 2015. In the UK, by 2013 e-cigarettes had outstripped NRT as the product of choice used by smokers wanting to quit
. Factors that have facilitated this phenomenon include the development of a globally-connected subculture of users, sophisticated internet marketing
, purchasing of devices and liquid by individuals anywhere in the world, and the development of long-life, low-weight, small rechargeable batteries that make these portable devices convenient, reliable and aesthetically attractive.
Role in smoking cessation
Patients use ECs for different reasons but the most widely reported ones are to quit smoking, to cut down the number of cigarettes smoked per day, and to use a product that is perceived as being ‘healthier’ than conventional cigarettes,
Smokers appear to have a preference for cigarette smoke compared with other forms of nicotine delivery,
. Therefore, ECs may have an advantage over current cessation treatments because they so closely approximate smoking visually and behaviourally. Many of the sensory and behavioural aspects of smoking, which smokers trying to quit usually miss — such as the non-nicotine rewards and critical sensory motor cues of the smoking hand-to-mouth action, visual cues or feelings in the throat — are simulated by using ECs,
Most ECs are as effective at delivering nicotine into the bloodstream as other nicotine-based smoking cessation treatments
. Some ECs are now able to generate an aerosol able to penetrate deep into the respiratory tract, enabling experienced vapers to achieve swift nicotine absorption into the pulmonary venous circulation that is equivalent to that observed with tobacco consumption,
. In studies with early devices and experienced EC users, a significant increase in plasma nicotine was obtained within five or ten minutes after the first puff,
, and in several studies salivary levels of cotinine were found to be similar to those of smokers,
A group of studies by research groups in three different countries testing different ECs between 2010 and 2013 demonstrated that ECs were capable of reducing tobacco cravings and withdrawal symptoms after an overnight period of cigarette abstinence,
. On the basis of these studies, their potential as smoking cessation treatments needed to be investigated. Several small non-randomised studies at around the same time reported quit rates ranging from 22% to 49%,
. However, the best evidence to date on the ability of ECs to help smokers quit comes from two randomised controlled trials (RCTs) that found sustained smoking abstinence rates ranging from 7% to 11%,
, similar to that of nicotine patches
A recent Cochrane review of ECs for smoking cessation that assessed 13 completed studies (including the two RCTs noted above and 11 cohort studies) concluded that nicotine ECs help smokers quit long term, compared with placebo ECs
. The authors rated their confidence in the result, using the Cochrane GRADE standard, as ‘low’ because of imprecision with a small number of trials
Since these two RCTs were conducted, ECs have changed considerably, most notably in terms of improved nicotine delivery profiles. The products evaluated in those trials are now obsolete; fewer than 5% of experienced vapers currently use these first generation products
. No adequately powered trials of second or third generation products have been published (although several trials using these newer devices are underway). One small RCT (n=48) reported higher quit rates (35% abstinent at two months; 19% at eight months) compared to trials with first generation ECs
. A cohort study of 591 smokers who had tried an EC and 1,051 smokers who had not found that daily users of a second (or better) generation EC were more likely to be abstinent from tobacco at follow-up (n=69; odds ratio [OR] 2.69 [1.48–4.89]) than those who had not tried ECs. Non-daily use of second generation ECs, and any use of first generation ECs, was associated with either no increase in cessation or less likelihood of cessation
Specific population groups with high smoking prevalence may find ECs helpful. ECs have been tried within current existing smoking cessation services and with a range of users. O’Brien et al. found that ECs were equally as effective as NRT for quitting, and were as safe and acceptable for people with and without mental illness. For people with mental illness, ECs may be as effective and safe as nicotine patches, yet more acceptable, and associated with greater smoking reduction
The Cochrane review found that ECs may help smokers cut down the number of cigarettes smoked compared with placebo
. It is not yet known if ‘dual use’ — using ECs but also continuing to smoke, albeit fewer, cigarettes — is just a step in the process of EC-driven smoking cessation, or if it may prolong the duration of what might have otherwise been a short cessation process. What is known is that cutting down the number of cigarettes smoked is a helpful strategy towards eventually quitting altogether and leads to less exposure to harmful toxicants than continued smoking. A recent Cochrane review found that reducing cigarettes smoked before a designated quit day led to equivalent quit rates as quitting abruptly without any prior reduction in the number of cigarettes smoked
. In a small UK study, smokers who were given an EC as part of specialist ‘stop smoking’ treatment, and who failed in their attempt to quit smoking but continued to use ECs, were exposed to fewer toxicants, compared with those who continued to smoke only tobacco cigarettes
, suggesting short-term ‘dual use’ is associated with a reduction in harm.
The increasing use of ECs has not been without controversy and there has been considerable debate in leading medical journals and the media over the safety of ECs. The main point of contention focuses on a fundamental question: are ECs of net benefit or harm to individuals and society? Within this debate lie a number of questions: are ECs introducing new forms of nicotine addiction, decreasing motivation to quit by alleviating the environmental pressures to quit
, or acting as a ‘gateway’ product for non-smokers, especially young people, to take up smoking,
? There is little question that many young people are experimenting with ECs
, but the vast majority of these are smokers and evidence for progression to ongoing cigarette use is limited. Wider concerns include the worry that ECs may ‘renormalise’ smoking behaviours just when cigarette smoking is becoming ‘not the norm’ in many societies, and that they could undermine the ‘end game’ for tobacco, playing into the tobacco industry’s hands.
With regards to safety at an individual level, there is concern about exposure to toxicants in EC vapour. Some studies have identified toxicants and these findings have attracted wide media coverage
. However, the overall level of risk to health from EC use is considered to be far lower than that of smoking. First, EC aerosol does not contain carbon monoxide, nor most of the toxicants found in cigarette smoke,
. Indeed, an authoritative national public health body, Public Health England, has stated in its recent report that ECs are 95% safer to use than smoking tobacco cigarettes
. This claim is based on work undertaken by an expert panel using a Delphi-like methodology that is widely used in other domains
. The panellists reviewed the evidence and concluded that the vast majority of harmful constituents in tobacco smoke are not found in EC vapour and, if present, are at levels that are orders of magnitude lower (i.e. in the range of 9 to 1,000 times lower). On a scale of risk of harm, they considered ECs were not only far less harmful than tobacco cigarettes, but only slightly more harmful than pharmaceutical grade nicotine products such as NRT
Mild adverse effects such as headaches, dry mouth or throat, throat or mouth irritation, dry cough or nausea have been reported by some users
. In general, users report few side effects,
, and may report health benefits compared with those who continue smoking as usual
. Research has found that current EC users improve their lung function because of smoking reduction via ECs
, as well as their working memory performance when ECs with nicotine are used compared with placebo
, a similar finding to that described by smokers who report that cigarettes aid concentration and cognition
. More recently, Farsolinas et al. found that smokers with elevated blood pressure (BP) who reduced or quit smoking by switching to ECs had a significant lowering in their systolic BP at 52 weeks after adjusting for weight change, gender and age
Government authorities and regulatory agencies were unprepared for the emergence of ECs. In general, there is a paucity of regulatory frameworks and instruments designed specifically to address the challenges such products present to individual and population health
. This is in part because of the way tobacco control policies and regulations have been configured, but also a result of the limited availability of research-based evidence on EC safety, quality and efficacy for smoking cessation that regulatory agencies usually require to approve pharmaceutical industry-sourced cessation products. Where research has been published, its validity has often been contested within the tobacco control research and advocacy communities
Uncertainty about hypothetical harms does not always justify imposing sanctions, especially when the costs and harms of such restriction are likely to far exceed the costs and harms of ‘light touch’ regulation based on what we know of the toxicology of ECs. There are now data on the chemical properties of EC aerosols, such that it is difficult to conceive that the extent of any negative health consequences from even decades of vaping will rival that produced by decades of inhaling toxic tobacco smoke. Even if there was an unknown adverse health effect, it is likely authorities could be waiting for several decades before any signal was apparent. Hall and others have suggested that those who propose to wait have an ethical obligation to specify what type of evidence would convince them to lift a ban on EC sales
. An appropriate approach would be to allow product availability while ensuring a robust regulatory requirement for product constituents, and use surveillance and enforcement was in place at each level of tobacco control and point of sale.
Current approaches to EC regulation vary from country to country. In the UK, the sale, advertising and use of ECs are permitted as long as they are marketed as a smoking alternative, in which case they come under consumer product regulations. No therapeutic claims — including as a smoking cessation aid — are allowed to be made; to do so would imply a medicinal function and a pharmaceutical license would be required.
The current directive before the European Parliament would permit ECs to be sold in European Union countries but it would also introduce a ban on all advertising and sponsorship, limit the strength of nicotine liquids to 20mg/ml, limit liquid container sizes, and require large warning labels
In the United States, ECs are currently ‘unregulated tobacco products’. The US Food and Drug Administration plan is to apply tobacco control legislation to ECs (the ‘deeming’ regulation), meaning that the Family Smoking Prevention and Tobacco Control Act will apply
Some countries, such as Australia and New Zealand, treat nicotine and non-nicotine products differently. Unless sold as closed disposable systems, companies are permitted to advertise and sell the devices themselves as long as they do not claim that they are smoking cessation aids. Liquids (in cartridges or refill bottles) without nicotine are also currently permitted. However, refills containing nicotine, or closed devices sold pre-filled with a nicotine-containing liquid, can only be sold with medical authorisation. While there is currently limited evidence to support the claims that ECs are a gateway to smoking
, there can be little disagreement that ECs should not be made attractive to young people and advertising should not appeal to young audiences
. More restrictive regulation should be applied to products with the highest abuse potential. For example, most people would agree that tobacco cigarettes should be heavily taxed because they are known to be lethal in almost half of long-term users. But it could be argued that ECs that have a low (but not absent) risk of harm should not be taxed at all, or taxed at a lower level than tobacco cigarettes. Too restrictive a regulatory regimen is unlikely to achieve the desired policy objective — to reduce smoking-related harm.
Given what is already known about these products, countries that permit the sale and use of ECs should consider introducing regulations, or using existing regulations, to provide consumers with greater confidence in product safety, quality and reliability, and to remove any unsafe products from the market.
Advice for smokers
At a minimum, all healthcare professionals should take every opportunity to encourage smokers to stop smoking and should assist them in their attempts to quit using evidence-based treatments and behavioural support. This is not an optional extra but an ethical imperative
Many people will ask about ECs, may have tried them, may be using them, or may be contemplating using them. They should be informed that ECs are a safer option than continuing to smoke tobacco and are probably as effective for smoking cessation as NRT. Those who are unwilling to quit smoking or who have tried the full range of evidence-based approaches available, yet repeatedly relapsed to smoking, should not be actively stopped from trying or continuing to use ECs if they are already using them. Rather, they should be offered support and should be advised that if they do use ECs, it is safest that they are used without continuing to smoke tobacco, even a single cigarette. If they find it hard to cut out cigarettes completely, then ‘dual use’ should be contemplated for a limited time only, with the intention of cutting down, and eventually cutting out, cigarettes altogether.
In addition to the wide range of products within the EC group, several novel inhalable nicotine devices that show promise are in development. These include products developed by tobacco companies, such as ‘heat not burn’ cigarettes, metered-dose aerosol systems, and the nicotine pyruvate inhaler. Such products, especially those being developed by the tobacco industry and their subsidiaries, present a challenge to the tobacco control community: while they have potential as new options for the many smokers seeking help to stop smoking and improve their health, they raise the issue of tobacco harm reduction as a valid tobacco control strategy and pose questions about engagement with industry. As ECs evolve and new reduced-harm products are developed, it is vital that healthcare professionals keep pace with innovation and evidence in this field to be able to guide people who smoke, the wider public and policymakers.
Chris Bullen is professor and director of the National Institute for Health Innovation (NIHI) School of Population Health, the University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Carla LÃ³pez-NÃºÃ±ez is a researcher and psychologist at Oviedo University, Spain. Oliver Knight-West is a psychologist based in the UK (formerly at University of Auckland, New Zealand). Correspondence to:
Financial and conflicts of interest disclosure:
Chris Bullen has received grants from the New Zealand Health Research Council. The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilised in the production of this manuscript.
Reading this article counts towards your CPD
You can use the following forms to record your learning and action points from this article from Pharmaceutical Journal Publications.
Your CPD module results are stored against your account here at The Pharmaceutical Journal. You must be registered and logged into the site to do this. To review your module results, go to the ‘My Account’ tab and then ‘My CPD’.
Any training, learning or development activities that you undertake for CPD can also be recorded as evidence as part of your RPS Faculty practice-based portfolio when preparing for Faculty membership. To start your RPS Faculty journey today, access the portfolio and tools at www.rpharms.com/Faculty
If your learning was planned in advance, please click:
If your learning was spontaneous, please click:
 US Department of Health and Human Services. The health consequences of smoking — 50 years of progress: a report of the Surgeon General. Rockville (MD): U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. 2014. Available at: http://www.surgeongeneral.gov/library/reports/50-years-of-progress/full-report.pdf (accessed March 2016).
 World Health Organization. Tobacco fact sheet NÂº339. 2014. Available at: http://www.who.int/mediacentre/factsheets/fs339/en/ (accessed March 2016).
 Cahill K, Stead L & Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systematic Reviews 2012;4:CD006103. doi: 10.1002/14651858.CD006103.pub6
 Stead L, Perera R, Bullen C et al. Nicotine replacement therapy for smoking cessation. Cochrane Database of Systematic Reviews 2012;14;11:CD000146. doi: 10.1002/14651858.CD000146.pub4
 Brugal MT, Domingo-Salvany A, Puig R et al. Evaluating the impact of methadone maintenance programmes on mortality due to overdose and aids in a cohort of heroin users in Spain. Addiction 2005;100(7):981–989. doi: 10.1111/j.1360-0443.2005.01089.x
 McNeill A & Munafo MR. Reducing harm from tobacco use. Journal of Psychopharmacology 2013;27(1):13–18. doi: 10.1177/0269881112458731
 Rodu B & Godshall WT. Tobacco harm reduction: an alternative cessation strategy for inveterate smokers. Harm Reduction Journal 2006;3:37. doi: 10.1186/1477-7517-3-37
 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(1):5–7. doi: 10.1007/s00204-013-1127-0
 Farsalinos K & 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. doi: 10.1177/2042098614524430
 National Institute for Clinical Excellence (NICE). Tobacco: harm-reduction approaches to smoking (2013). London: NICE. Available from: https://www.nice.org.uk/guidance/ph45 (accessed 1 December 2014).
 Polosa R, Rodu B, Caponnetto P et al. A fresh look at tobacco harm reduction: the case for the electronic cigarette. Harm Reduction Journal 2013;10:19. doi: 10.1186/1477-7517-10-19
 Adriaens K, Van Gucht D, Declerck P et al. Effectiveness of the electronic cigarette: an eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health 2014;11(11):11220–11248. doi: 10.3390/ijerph111111220
 Farsalinos K, Romagna G, Tsiapras D et al. Evaluation of electronic cigarette use (vaping) topography and estimation of liquid consumption: implications for research protocol standards definition and for public health authorities’ regulation. Int J Environ Res Public Health 2013;10(6):2500–2514. doi: 10.3390/ijerph10062500
 McRobbie H, Bullen C, Hartmann-Boyce J et al. Electronic cigarettes for smoking cessation and reduction. Cochrane Database of Systematic Reviews 2014;12:CD010216. doi: 10.1002/14651858.CD010216.pub2
 Foulds J, Veldheer S & Berg A. Electronic cigarettes (e-cigs): views of aficionados and clinical/public health perspectives. Int J Clin Pract 2011;65(10):1037–1042. doi: 10.1111/j.1742-1241.2011.02751.x
 Dawkins L & Corcoran O. Acute electronic cigarette use: nicotine delivery and subjective effects in regular users. Psychopharmacology (Berl) 2014;231(2):401–407. doi: 10.1007/s00213-013-3249-8
 Farsalinos K, Spyrou A, Tsimopoulou K et al. Nicotine absorption from electronic cigarette use: comparison between first and new-generation devices. Scientific Reports 2014;4:7. doi: 10.1038/srep04133 10.1038/srep04133
 Zhu SH, Sun JY, Bonnevie E et al. Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation. Tob Control 2014;23(Suppl 3):iii3–9. doi: 10.1136/tobaccocontrol-2014-051670
 Farsalinos K, Romagna G, Tsiapras D et al. Impact of flavour variability on electronic cigarette use experience: an internet survey. Int J Environ Res Public Health 2013;10(12):7272–7282. doi: 10.3390/ijerph10127272
 Goniewicz ML, Kuma T, Gawron M et al. Nicotine levels in electronic cigarettes. Nicotine & Tobacco Research 2013;15(1):158–166. doi: 10.1093/ntr/nts103
 Goniewicz ML, Hajek P & McRobbie H. Nicotine content of electronic cigarettes, its release in vapour and its consistency across batches: regulatory implications. Addiction 2014;109(3):500–507. doi: 10.1111/add.12410
 Orr KK & Asal NJ. Efficacy of electronic cigarettes for smoking cessation. Annals of Pharmacotherapy 2014;48(11):1502–1506. doi: 10.1177/1060028014547076
 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. Int J Environ Res Public Health 2014;11(4):4356. doi: 10.3390/ijerph110404356
 Brown J, Beard E, Kotz D et al. Realâworld effectiveness of eâcigarettes when used to aid smoking cessation: a crossâsectional population study. Addiction 2014;109(9):1531–1540. doi: 10.1111/add.12623
 Noel JK, Rees VW & Connolly GN. Electronic cigarettes: a new ‘tobacco’ industry? Tob Control 2011;20:81. doi: 10.1136/tc.2010.038562
 Etter JF. Electronic cigarettes: a survey of users. BMC Public Health 2010;10:231. doi: 10.1186/1471-2458-10-231
 Pepper JK & Brewer NT. Electronic nicotine delivery system (electronic cigarette) awareness, use, reactions and beliefs: a systematic review. Tob Control 2014;23(5):375–384. doi: 10.1136/tobaccocontrol-2013-051122
 Rose JE, Behm FM, Westman EC et al. Dissociating nicotine and nonnicotine components of cigarette smoking. Pharmacology Biochemistry and Behavior 2000;67(1):71–81. doi: 10.1016/s0091-3057(00)00301-4
 Westman EC, Behm FM & Rose JE. Dissociating the nicotine and airway sensory effects of smoking. Pharmacology Biochemistry and Behavior 1996;53(2):309–315. doi: 10.1016/0091-3057(95)02027-6
 Barbeau AM, Burda J & Siegel M. Perceived efficacy of e-cigarettes versus nicotine replacement therapy among successful e-cigarette users: a qualitative approach. Addiction Science & Clinical Practice 2013;8:5. doi: 10.1186/1940-0640-8-5
 Bell K & Keane H. Nicotine control: e-cigarettes, smoking and addiction. International Journal of Drug Policy 2012;23(3):242–247. doi: 10.1016/j.drugpo.2012.01.006
 Palazzolo DL. Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review. Frontiers in Public Health 2013;1:56. doi: 10.3389/fpubh.2013.00056
 Bullen C. Electronic cigarettes for smoking cessation. Curr Cardiol Rep 2014;16(11):538. doi: 10.1007/s11886-014-0538-8
 Zhang Y, Sumner W & Chen DR. In vitro particle size distributions in electronic and conventional cigarette aerosols suggest comparable deposition patterns. Nicotine & Tobacco Research 2013;15(2):501–508. doi: 10.1093/ntr/nts165
 Vansickel AR & Eissenberg T. Electronic cigarettes: effective nicotine delivery after acute administration. Nicotine & Tobacco Research 2013;15(1):267–270. doi: 10.1093/ntr/ntr316
 Etter JF & Bullen C. Saliva cotinine levels in users of electronic cigarettes. European Respiratory Journal 2011;38(5):1219–1220. doi: 10.1183/09031936.00066011
 Bullen C, McRobbie H, Thornley S et al. Effect of an electronic nicotine delivery device (e-cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial. Tob Control 2010;19(2):98–103. doi: 10.1136/tc.2009.031567
 Dawkins L, Turner J, Hasna S et al. The electronic-cigarette: effects on desire to smoke, withdrawal symptoms and cognition. Addict Behav 2012;37(8):970–973. doi: 10.1016/j.addbeh.2012.03.004
 Etter JF & Bullen C. Electronic cigarette: users profile, utilization, satisfaction and perceived efficacy. Addiction 2011;106(11):2017–2028. doi: 10.1111/j.1360-0443.2011.03505.x
 Vansickel AR, Cobb CO, Weaver MF et al. A clinical laboratory model for evaluating the acute effects of electronic “cigarettes”: nicotine delivery profile and cardiovascular and subjective effects. Cancer Epidemiology, Biomarkers & Prevention 2010;19(8):1945–1953. doi: 10.1158/1055-9965.EPI-10-0288
 Vansickel AR, Weaver MF & Eissenberg T. Clinical laboratory assessment of the abuse liability of an electronic cigarette. Addiction 2012;107(8):1493–1500. doi: 10.1111/j.1360-0443.2012.03791.x
 Polosa R, Caponnetto P, Morjaria JB et al. Effect of an electronic nicotine delivery device (e-cigarette) on smoking reduction and cessation: a prospective 6-month pilot study. BMC Public Health 2011;11:786. doi: 10.1186/1471-2458-11-786
 Siegel MB, Tanwar KL & Wood KS. Electronic cigarettes as a smoking-cessation: tool results from an online survey. American Journal of Preventive Medicine 2011;40(4):472–475. doi: 10.1016/j.amepre.2010.12.006
 Bullen C, Howe C, Laugesen M et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet 2013;382(9905):1629–1637. doi: 10.1016/S0140-6736(13)61842-5
 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. doi: 10.1371/journal.pone.0066317
 Hitchman SC, Brose LS, Brown J et al. Associations between e-cigarette type, frequency of use, and quitting smoking: findings from a longitudinal online panel survey in Great Britain. Nicotine & Tobacco Research 2015;17(10):1187–1194. doi: 10.1093/ntr/ntv078
 O’Brien B, Knight-West O, Walker N et al. E-cigarettes versus NRT for smoking reduction or cessation in people with mental illness: secondary analysis of data from the ASCEND trial. Tobacco Induced Disease 2015;13(1):5. doi: 10.1186/s12971-015-0030-2
 Lindson-Hawley N, Aveyard P & Hughes J. Reduction versus abrupt cessation in smokers who want to quit. Cochrane Database of Systematic Reviews 2012;11:CD008033. doi: 10.1002/14651858.CD008033.pub3
 Hajek P, Goniewicz ML, Myers Smith K et al. Effect on acrolein delivery of the use of electronic cigarettes with and without current smoking. Paper presented at the 2014 Proceedings of the Annual Meeting of the Society for Research on Nicotine & Tobacco, Seattle, United States.
 Grana RA. Electronic cigarettes: a new nicotine gateway? The Journal of Adolescent Health 2013;52(2):135–136. doi: 10.1016/j.jadohealth.2012.11.007
 Cobb NK & Abrams DB. E-cigarette or drug-delivery device? Regulating novel nicotine products. N Engl J Med 2011;365(3):193–195. doi: 10.1056/NEJMp1105249
 Al-Delaimy WK, Myers MG, Leas EC et al. E-cigarette use in the past and quitting behavior in the future: a population-based study. Am J Public Health 2015:105(6);1213–1219. doi: 10.2105/ajph.2014.302482
 Arrazola R, Singh T, Corey C et al. Tobacco use among middle and high school students — United States, 2011–2014. MMWR Morbidity Mortality Weekly Reports 2015;17;64(14):381–385. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6414a3.htm (accessed March 2016).
 Jensen RP, Luo W, Pankow JF et al. Hidden formaldehyde in e-cigarette aerosols. N Engl J Med 2015;372(4):392–394. doi: 10.1056/NEJMc1413069
 Public Health England. E-cigarettes: An evidence update (2015). London: Public Health England. Available from: www.gov.uk/government/publications/e-cigarettes-an-evidence-update
 Nutt DJ, Phillips LD, Balfour D et al. Estimating the harms of nicotine-containing products using the MCDA approach. European Addiction Research 2014;20(5):218–225. doi: 10.1159/000360220
 Heishman SJ, Kleykamp BA & Singleton EG. Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology (Berl) 2010;210(4):453–469. doi: 10.1007/s00213-010-1848-1
 Farsalinos K, Cibella F, Caponnetto P et al. Effect of continuous smoking reduction and abstinence on blood pressure and heart rate in smokers switching to electronic cigarettes. Internal and Emergency Medicine 2016. PMID: 26749533
 Benowitz NL & Goniewicz ML. The regulatory challenge of electronic cigarettes. JAMA 2013;15(10):109501. doi: 10.1001/jama.2013.109501
 Etter J-F. Should electronic cigarettes be as freely available as tobacco? Yes. BMJ (Clinical research ed) 2013;346:f3845. doi: 10.1136/bmj.f3845
 Hall W, Gartner C & Forlini C. Ethical issues raised by a ban on the sale of electronic nicotine devices. Addiction 2015;110(7):1061–1067. doi: 10.1111/add.12898
 European Union Directive 2014/40/EU Tobacco Products Directive. (2014).
 US Food and Drug Administration. Press release. 24 April 2014. Available from: www.fda.gov/newsevents/newsroom/pressannouncements/ucm394667.htm (accessed March 2016).
 Hajek P, Etter J-F, Benowitz N et al. Electronic cigarettes: review of use, content, safety, effects on smokers and potential for harm and benefit. Addiction 2014;109(11):1801–1810. doi: 10.1111/add.12659
 Bullen C, Whittaker R, McRobbie H et al. A clinical imperative: assisting patients who smoke to reduce their risk of cardiovascular disease. Preventive Cardiology 2007;10(2):5–9. doi: 10.1111/j.1520-037X.2007.06525.x