This is the first time that objective measures of smoking cessation are reported in smokers with a documented history of recurring relapses, who quit smoking after taking up an E-cigarette with the intention of quitting tobacco smoking. This was accomplished by heavy smokers who repeatedly failed in previous attempts with professional smoking cessation assistance based on the usual nicotine dependence treatments and smoking cessation counselling. Some studies have found that multiple failed attempts have a negative effect on a smoker's confidence in being able to quit smoking cigarettes .
The COPD patient was a particularly difficult case with an FTND of 10 (maximum score) and a documented history of recurring relapses. The available evidence in the medical literature indicates that, in contrast with smokers in the general population, COPD patients who smoke typically respond poorly to smoking cessation efforts; they have a greater degree of physical nicotine dependence  and appear to be less motivated to quit smoking .
We cannot discount that the success observed in our patients may be simply due to the repeated number of quit attempts and not necessarily to E-cigarette use. However, we later contacted these patients and asked if they took up the E-cigarette with the intention to quit and if they believed that they would not have quit if it weren't for the E-cigarettes. Answers to both questions were positive for all three patients. Thus, these patients felt that they would not have quit tobacco smoking without the help of E-cigarettes.
The remarkable success stories of these three smokers require consideration. The widely acknowledged beneficial role of pharmacotherapy in smoking cessation is likely to be due to its ability to address the physical component of tobacco dependence. However, taking pills or patches for nicotine addiction is unlikely to resolve the psychological components associated with tobacco dependence. As a matter of fact smoking is much more than the addicting effect of nicotine; the smoking habit also includes the rituals that each smoker associates with his or her habit . Smoking cessation products cannot replace the rituals associated with the act of smoking.
Counselling for smoking cessation is intended to help smokers in coping with this important aspect of their life by implementing personalized replacement rituals, but even counselling for smoking cessation lacks high levels of efficacy. Therefore, it is likely that the smokers described in our case series coped successfully with the psychological components associated with their tobacco dependence by using a device resembling a cigarette, which - although being mainly designed for the purpose of nicotine delivery to the respiratory system - has the additional advantage of being a valid substitute for the tactile sensations of the cigarette and other sensations associated with smoking gestures.
An important aspect that needs to be highlighted in relation to the findings of the present case series is the putative risk of E-cigarettes. In June 2009, the US Food and Drug Administration (FDA) announced in a press conference that 'a laboratory analysis of electronic cigarette samples has found that they contain carcinogens and toxic chemicals such as diethylene glycol (DEG), an ingredient used in antifreeze' . The actual lab report revealed that the 'carcinogens' referred to in the FDA's press conference were tobacco specific nitrosamines (TSNAs), but failed to specify the quantity detected. The FDA's report did state that the quantity of DEG detected in the liquid in one of the 18 samples was 1% (0.01 ml), but did not point out that this is a non-toxic quantity. The FDA did not report finding DEG, or any other harmful chemical, in the vapor . A number of reports available over the Internet have subsequently characterized, quite extensively, the components contained in E-cigarette liquid and vapor using gas chromatography mass spectrometry (GC-MS). They demonstrate that the primary components of E-cigarette cartridges are propylene glycol (PG), glycerin, and nicotine . Laugesen tested E-cigarette mist for more than 50 priority-listed cigarette smoke toxicants and found none . This report only revealed traces (8.2 ng/g) of TSNAs in the 'high' nicotine cartridge of an E-cigarette.
It must be noted that this amount is equal to the quantity reported to be present in a nicotine medicinal patch.
Recently, Cahn and Siegel have reviewed the results of 16 laboratory analyses of E-cigarette liquid, including the FDA's 'Final Report'. TSNAs were reported in two studies, but at trace levels, which are similar to those found in a nicotine patch, and, most importantly, about 500-fold to 1400-fold lower than TSNA levels measured in regular cigarettes. The presence of DEG was reported in the FDA's report in one of the 18 cartridges, yet none of the other 15 studies found any DEG. The authors stated, 'Other than TSNAs and DEG, few, if any, chemicals at levels detected in E-cigs raise serious health concerns. Although the current data are insufficient to conclude that E-cigarettes are safe in absolute terms and that further studies are needed to comprehensively assess their safety, these products appear to be much safer than tobacco cigarettes and comparable in toxicity to conventional nicotine replacement products' .
In a recent prospective proof-of-concept study, we monitored possible modifications in the smoking habits of 40 smokers not willing to quit who were experimenting with a 7.4 mg nicotine/cartridge E-cigarette . Combined sustained smoking reduction and smoking abstinence was shown in 55% of the participants, with an overall 88% fall in the number of cigarettes smoked per day. Mouth and throat irritation, and dry cough were common, but diminished substantially by the end of the study. Retailers all over the world have already sold hundreds of thousands of E-cigarettes, yet there is no evidence that these products have endangered anyone.
Lastly, there may be some concern that non-smokers might take up use of an E-cigarette, become addicted to nicotine, and eventually start to smoke tobacco cigarettes. The fear of this 'gateway effect' has been mentioned in connection with the European Union ban on the sale of snus, a type of smokeless tobacco that is neither chewed nor smoked. The available evidence would indicate that snus provides a gateway out of smoking rather than into it. Snus is a type of finely ground moist snuff that delivers significant levels of nicotine. Snus does not produce any of the toxic combustion products and it is manufactured in a way that produces low levels of tobacco-specific nitrosamines, the main carcinogens responsible for oral cancers in users of other smokeless tobacco products .
Sweden now has one of the lowest smoking prevalence rates in the world . Ranstrom and Foulds found the odds of initiating daily smoking were significantly lower for men who had started using snus than for those who had not (odds ratio (OR) = 0.28, 95% confidence interval (CI) 0.22 to 0.36) . Another study found that the quit ratio for smoking was significantly higher for daily snus users in six of seven data sets collected during 2003 to 2008 in Norway . In the United States of America (USA) 73% of the most recent quit attempts using smokeless tobacco resulted in smokers achieving smoking abstinence .
In a survey that included 3037 ever-users of E-cigarettes, only one of the 2850 respondents who used nicotine-containing E-cigarettes was a never-smoker . The authors of the study did not report the reason. Given the fact that 70% of the ever-users succeeded in quitting smoking, the E-cigarette would also appear to be a gateway away from smoking. In previous quit attempts, 70.5% had tried nicotine therapy, 29.1% used bupropion, and 19.4% used varenicline. Users of both snus and E-cigarettes might be less likely to later switch to smoking if governments and health organizations made it clear that smoking carries enormously greater health risks than nicotine that comes from non-smoked sources.
Obviously, these products need to be adequately regulated, but thus far, there have been heterogeneous regulatory responses. Some countries have completely banned the sale and marketing of E-cigarettes whereas others allow marketing within their regulatory frameworks. Internet marketing of E-cigarettes and the inadequacy and misapplication of import product codes, however, impede systematic regulation . More research on E-cigarettes must be conducted in order to ensure that the decisions of regulators, healthcare providers and consumers are evidence-based.