The Emerging Phenomenon of Electronic Cigarettes

Pasquale Caponnetto; Davide Campagna; Gabriella Papale; Cristina Russo; Riccardo Polosa


Expert Rev Resp Med. 2012;6(1):63-74. 

In This Article

Electronic Cigarettes: What About the Clinical Evidence?

The electronic cigarette is a very hot topic that has generated considerable global debate, with some authorities wanting to ban it or, at least, regulate it. Consequently, a formal demonstration supporting the efficacy and safety of these devices in clinical trials is of the utmost importance.

One of the earliest clinical trials of electronic cigarettes was conducted at the University of Auckland (New Zealand). Forty adult smokers of ten or more cigarettes per day were randomized to use an electronic cigarette containing 16 mg of nicotine or 0 mg of nicotine (placebo), a Nicorette® (McNeil Healthcare Ltd, Wokingham, UK) nicotine inhalator or their own brand cigarette. The 16-mg electronic cigarette alleviated the desire to smoke after overnight abstinence, was well tolerated and exhibited a pharmacokinetic profile more similar to the Nicorette inhalator than a tobacco cigarette.[6] A US study of 32 smokers comparing two brands of electronic cigarettes to the participants' own brand found that ten puffs from either brand delivered little to no nicotine compared with ten puffs from the regular brand. However, both models effectively suppressed nicotine-withdrawal symptoms.[23] Canadian researchers examined the reinforcing effects of electronic cigarettes with and without nicotine on 11 volunteers. Participants reported a reduction in craving, regardless of the nicotine content.[24] The fact that the observed beneficial effects on craving and withdrawal symptoms appear to be independent of the nicotine content in the electronic cigarettes requires explanation. The well-known powerful interaction between physical and behavioral dependence of smoking[25,26] suggests that the reported positive effects of the electronic cigarette may also be owing to its capacity to provide a coping mechanism for conditioned smoking cues by replacing some of the rituals associated with smoking gestures for some smokers (e.g., the hand-to-mouth action of smoking), even if little or no nicotine is present. In agreement with this, we have recently demonstrated that nicotine-free inhalators can only improve quiting rates in those smokers for whom handling and manipulation of their cigarette played an important role in their ritual of smoking.[18]

In two recent case series, we have reported objective measures of long-term smoking abstinence in challenging smokers with severe nicotine dependence and/or major depression who have quit after taking up an electronic cigarette.[27,28] This is quite outstanding when considering the fact that this result was accomplished without the support of recommended nicotine-dependence treatments and smoking-cessation counseling, and with individuals who had repeatedly failed in previous attempts when provided with professional smoking-cessation assistance.

In our recent prospective 6-month proof-of-concept study, important modifications in smoking habits were reported in 40 smokers (not currently attempting to quit smoking or wishing to do so in the next 30 days) after using a commercial brand of electronic cigarette (Categoria electronic cigarette) loaded with a 7.4-mg nicotine cartridge.[12] Study participants were invited to attend a total of five study visits. During the first baseline visit, basic demographic and a detailed smoking history were taken. Additionally, levels of carbon monoxide in exhaled breath were measured. Participants were then given a free electronic cigarette kit containing two rechargeable batteries, a charger and two atomizers, and instructed on how to charge, activate and use the electronic cigarette. A free supply of 7.4-mg nicotine cartridges ('original' cartridges; Arbi Group Srl) was also provided throughout the study and participants were trained on how to load them onto the electronic cigarette's atomizer. Participants were invited to use it whenever they wanted and to attend four follow-up visits at weeks 4, 8, 12 and 24. At these visits we recorded their exhaled carbon monoxide levels and collected completed study diaries and unused study products. In this pilot study, we have shown for the first time that substantial and objective modifications in the smoking habits may occur in smokers using electronic cigarettes, with significant smoking reduction and smoking abstinence, and no apparent increase in withdrawal symptoms. Participants were not only enthusiastic about using the electronic cigarettes, but the majority (67.5%) were also able to adhere to the program and to return for the final follow-up visit at week 24, with an overall quit rate of 22.5% (Figure 4). Moreover, at least a 50% reduction in cigarette smoking was observed in 32.5% of participants. Overall, combined reduction and smoking abstinence was shown in 22 out of 40 (55%) participants, with an overall 88% fall in the number of cigarettes smoked per day. It is, however, possible that technical problems (particularly the product failures that went unreported) and difficulty of use (it takes time to familiarize with the puffing technique) could have had a negative influence on the total number lost to follow-up and smoking cessation/reduction failures, and that a more positive outcome would be obtainable with the new improved models. Conversely, the 'novelty' effect of this new product could explain its widespread adoption, with many smokers willing to show off their new gadget in front of their fellow smokers and to the public.

Figure 4.

Participants' smoking status after 24 weeks of electronic cigarette use.
This illustration was developed based on the findings of the study by Polosa et al. [12].

The findings of this study are of great significance in view of the fact that all smokers in the study were, by inclusion criteria, not interested in quitting. Although not directly comparable with classic cessation and/or reduction studies with other pharmaceutical products because of its design (the present study is not an ordinary cessation study and the study population included smokers not willing to quit), the results of our study are in general accordance with the findings published in the medical literature.[29] The fact that a substantial number of smokers unwilling to quit eventually switched to the electronic cigarette or quit altogether requires explanation. It is possible that for some participants, satisfaction from electronic cigarette use was good enough to compensate for their need of own brand cigarette. This by itself can explain the behavior change in the nine participants (22.5%) who were not smoking at week 24. The replacement of the ritual of smoking gestures, the opportunity to reduce a bad smell, to reduce cost of buying traditional cigarettes and the perception of an improved general sense of wellbeing might have been responsible for their switching/quitting.

Although the data presented here are encouraging, large and carefully conducted prospective, randomized controlled trials will be required before a definite answer about the efficacy of these products can be formulated. Some of these trials are already in progress in Italy[208–210] and New Zealand,[211] and hopefully they will be able to confirm and expand the positive preliminary clinical experience with these products.


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