I’m happy to respond to your comments.

Your first point is absolutely correct, and I’m sorry to say that reference 3 is clearly the wrong reference. Instead, read this CDC report on e-cig use among teens http://www.cdc.gov/media/.... This report suggests that e-cig use among teens and non-smokers is a concern. These concerns are echoed in a recent study (Moore 2014 Tob Control). I’m aware of a study in adults showing that very few never smokers try e-cigs. It seems that the popularity of e-cigs is greater among non-smoking teens than among non-smoking adults.
In response to your comment regarding the usefulness of e-cigs as an aid for smoking cessation, there are some studies that suggest e-cigs may have some benefit over using no cessation aids. A recent well-written review (Grana Circulation. 2014 May 13;129(19):1972-86.) compared the results of five smoking cessation studies comparing e-cig use as a cessation aid vs no cessation aid. Two of these five studies showed significant increases in cessation rate, while the other three studies did not demonstrate clear benefit. Several other studies have also been published showing varying levels of efficacy. Many of these studies were limited by small sample sizes and reliance on self-reporting for cessation. Additionally, some studies were funded by e-cig manufacturers, or included messages to participants that e-cigs are a healthier alternative to smoking. Considering your repeated accusation that our study was biased, this criticism of other studies seems appropriate. An additional caveat to these studies is that several of the participants who successfully quit smoking continued to use e-cigs. So these individuals did not break their nicotine habit, but instead switched to a different form of nicotine. Whether or not that is a good thing, is a hotly debated topic. Thus despite numerous studies, there are still questions relating to their effectiveness as a smoking cessation aid.

In one large study that compared smoking cessation rates among 657 smokers wanting to quit, the authors showed that use of nicotine patches resulted in 5.8% smoking cessation, nicotine-free e-cigs resulted in 4.1% smoking cessation, and nicotine-containing e-cigs resulted in 7.3% smoking cessation, after 6 months (Bullen et al Lancet 2013). These differences were not significantly different from each other, and I would argue that none of them could be considered an effective device for smoking cessation. A policy statement from the American Lung Association states that “The FDA has not approved any e-cigarette as a safe or effective method to help smokers quit. When smokers are ready to quit, they should call 1-800-QUIT NOW or talk with their doctors about using one of the seven FDA-approved medications proven to be safe and effective in helping smokers quit.“ We acknowledge that the usefulness of E-cigs as an aid for smoking cessation is still open for debate and additional studies are warranted. In time, it is possible that e-cigs could become the eighth FDA-approved medication, but considering the level of regulation that would be required for this, it is unlikely. Regardless, it was never our intention in this publication to conduct a literature review on the effectiveness of e-cigs as a smoking cessation aid, nor did we test any aspect of this in our study. So perhaps our brief comment in the introduction that e-cigs may not be an effective therapy for smoking cessation did not adequately address this topic.

In regard to your point that our study was wrong to compare e-cig exposure vs room air exposure, we disagree. The questions of whether e-cigs are safe and whether they’re safer than cigarettes are both valid questions. The rising popularity of e-cigs among non-smokers further validates the rationale for this study. Additionally, it is a common perception that e-cigs are not only safer than cigarettes, but are harmless. Some of the reasons that are cited for this viewpoint include claims that e-cigs are only water vapor (which is incorrect), that they don’t contain tar, are free of carcinogens, and that they do not burn anything.

While the questions of safe and safer are both valid, it is fair to say that our study tackled the easier question. Our first goal was to establish a realistic model, in which mice inhaled e-cig vapor at a concentration that could be considered relevant. This was not a trivial task, and we feel that we were successful in this regard. Our next goal was to expose mice for a relatively brief period of time and see whether this exposure resulted in measureable effects in the lungs. We followed this up by putting the mice in a scenario where they developed a viral or bacterial respiratory infection to assess how e-cig exposure altered their response. Now that we have established a model for exposure and demonstrated that e-cig exposure induces a response, the logical future studies will focus on the relative response in comparison to cigarettes. However, we were not naïve to think that no one will ask us to put this study in context of cigarette smoke, and our manuscript makes numerous references to cigarette smoke. It’s easy to criticize this study by pointing out what wasn’t measured, and we acknowledge that there are limitations to this study.

We strongly agree with you that more studies are needed, and we hope that the NIH shares our view. You also criticize our choice to use “cheap disposable e-cigarettes using cheaply made atomisers and filled with poor quality liquid”. We used a commercial vendor that is a major player in the US e-cig market. We will be happy to test other brands; although as I’m sure you recognize, e-cigs come in an array of shapes and sizes, which presents a challenge for automating the exposures.
Lastly, I strongly disagree with you that anything presented in this study should be classified as dangerous.

Respectfully,
Thomas Sussan