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The potential presence of formaldehyde cyanohydrin in the polylactic acid (PLA) filter of Marlboro Heatstick when heated was reported by Davis and al. PLA is a biodegradable thermoplastic derived from renewable resources such as corn starch. This tentative identification is based on the GC-MS analysis of the headspace of a heated piece of PLA, and the subsequent compound identification by mass spectra matching (acceptance criteria >85%) with the spectra library of the National Institute of Standard and Technology (NIST). However, this was not confirmed by injecting a purchased analytical grade reference standard, in order to unambiguously prove the presence of formaldehyde cyanohydrin. Therefore, we decided to repeat the experiment using headspace injection gas chromatography coupled to high resolution mass spectrometry under similar conditions as described in the publication. Our headspace GC-HR-MS analyses showed four peaks, at retention times of 16.38, 16.47, 17.14, and 18.58 min, in good agreement with the reported data reported (figure 4).

From the analysis of reference standards, we have confirmed the presence of both e-caprolactone (CAS# 502-44-3) and (S,S)-lactide (CAS# 4511-42-6) eluting at 16.47 and 17.14 min, respectively. We identified triacetin (CAS# 102-76-1) at 18.58 min, based on the reference standard, instead of 1,2-diacetin (their EI mass spectra are very similar).
However, we have demonstrated unambiguously the absence of formaldehyde cyanohydrin by injecting the reference standard (Sigma, CAS# 107-16-4, ref. 50640). The formaldehyde cyanohydrin is eluting at 11.53 min and does not correspond to the peak eluting just before e-caprolactone that the authors tentatively identified as formaldehyde cyanohydrin (17.97 min under their conditions). This peak has been confirmed, using the purchased reference standard (NatureWorks, CAS # 13076-19-2), to be meso-lactide, the third isomers of lactide. The experimental details are available on PMIScience.com (https://www.pmiscience.com/library/publication/analysis-of-polylactic-ac...).
It is well known among analytical chemists that unit mass matching with a single data base is insufficient to prove the identity of a compound. Therefore, we typically use commercially available reference standards to verify our findings. This is important to us, as we are focused on developing reduced risk alternatives to combustible cigarettes. In this context, it is key that our science is always verified to the highest possible standards.

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Coleman et al’s important report [1] on transitions in the vaping and smoking status of a nationally representative cohort of American 18+ adults who use electronic cigarettes (EC) from the PATH study provides rich data that can greatly advance our understanding of the natural history of EC use and their potential in harm reduction.

However, we were struck by the absence of emphasis in the report of what is perhaps its most important finding. If we examine the report’s data and consider the net impact of vaping on the critical goals of having vapers stopping smoking and vaping non-smokers not starting to smoke, the findings are very disturbing and should strong reason for pause among those advocating e-cigarettes as a game-changing way of stopping smoking.

At Wave 2, 12 months on from Wave 1, of the cohort of 2036 dual users (EC + smoking) only 104 (5.1%) had transitioned to using only EC and another 143 (7%) had quit both EC and smoking for a combined total of 247 or 12.1%. Of the 896 exclusive EC users at Wave 1, 277 (30.9%) had stopped vaping at Wave 2. Together, 524 out of the 2932 EC users (17.9%) followed from Wave 1 might be considered to have had positive outcomes at Wave 2.

The other side of the coin however, shows that of the 2036 dual users at Wave 1, 886 (43.5%) relapsed to using cigarettes exclusively. In addition, among the 896 exclusive EC users from Wave 1, 109 (12.2%) had stopped vaping and were now smoking, with another 121 having resumed smoking as well as using EC (i.e. became dual users). Importantly, 502 of 896 (56%) exclusive e-cigarette users were those who had never been established smokers prior to using e-cigarettes. Alarmingly, of these 502 adults, 120 (23.9%) progressed from using only e-cigarettes to either dual use (54 or 10.8%) or smoking only (66 or 13.2%).

Taken together, 886 dual users in Wave 1 relapsed to become exclusive cigarette smokers in Wave 2, and 230 exclusive vapers in Wave 1 took up cigarette smoking in Wave 2 (dual use or exclusively cigarettes). Undoubtedly, these should be considered as negative outcomes.

The table below shows that for every person vaping at Wave 1 who benefited across 12 months by quitting smoking, there are 2.1 who either relapsed to or took-up smoking. Most disturbingly, in this adult cohort nearly one in four of those who had never been established smokers took up smoking after first using EC. Concern about putative gateway effects of ECs to smoking have been dominated by concerns about youth. These data showing transitions from EC to smoking in nearly a quarter of exclusive adult EC users with no histories of established smoking should widen this debate to consider adult gateway effects too.

By far the largest proportion of those with negative outcomes are those dual users who relapsed to smoking (886 or 43.5% of dual users). As the authors note in their discussion, many of these were infrequent EC users, possibly involved in transitory experimentation at Wave 1. If we add the 902 who were still dual using at Wave 2, then 1788 of 2036 dual users (87.8%) in this sample might be said to have been held in smoking (dual using or exclusive smoking) 12 months later compared to 12.1% dual users who may have benefitted by using ECs.

We would expect commercial interests in both the tobacco and EC industries would be more than delighted with these findings. However, from a public health harm reduction perspective these results argue against EC being an effective harm reduction strategy, and point to their far stronger potential to both recruit smokers and hold many smokers in smoking.

A table summarizing the above data can be found here: https://ses.library.usyd.edu.au/bitstream/2123/18240/3/Missing%20Elephan...

Reference
1. Coleman B et al Transitions in electronic cigarette use among adults in the Population Assessment of Tobacco and Health (PATH) Study, Waves 1 and 2 (2013-2105). Tobacco Control 2018; doi:10.1136/tobaccocontrol-2017-054174

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The reporting of the results of this study is far from complete, which is concerning given the highly politicised controversy that surrounds this product. I hope the authors should respond to this comment by publishing supplementary material with all the data they collected in a an accessible form such a CSV file and summarised in tables in a supplementary memo.

In particular, the authors should provide all data on the following:
+ Vaping and JUUL current use (used in past 30-days) prevalence stratified by age, clearly differentiating between 18 and over and under-18s
+ Frequency of use of vaping products and JUUL within the 30 days among current (past-30 days) users, ideally using the same frequency breakdown used in the National Youth Tobacco Survey
+ Breakdown of vaping status by smoking status and frequency of vaping and JUUL use - to help determine the extent to which regular JUUL use is concentrated among smokers
+ Smoking prevalence and frequency

There is a rare opportunity to gain insights into a live controversy, yet the reporting of the survey is so incomplete it is difficult to draw any serious conclusions from it about the overall effect. For example, JUUL maybe displacing other vaping products used by youth as it is in the market overall. JUUL may be functioning as an alternative to smoking in both adolescents and adults and contributing to achieving smoke-free public health objectives.

The Truth Initiative is proud of its advocacy for young people, but as far as presentation and interpretation of data are concerned, such activist commitment amounts to a competing interest. For that reason, everyone, including Truth, is served by full disclosure of the survey data in an appropriate and accessible form and answers to key data questions that would help understand the JUUL phenomenon.

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In the article Potential deaths averted in USA by replacing cigarettes with e-cigarettes (1), a Status Quo model is performed, which suggests that this change will avoid premature deaths of millions. Although the statement is interesting, it´s necessary to mention that, the quantity of cigarettes consumed wasn´t considered. In addition, it´s important to recognize that a controversy still exists about the use of these devices and their toxicity.

Believing that e-cigarettes are an alternative against the use of cigarettes is tempting, but we have to be cautious. One of the major risk factors for cancer is an excessive consumption of cigarettes. In Müezzinler A et al (2), a dose response between the number of cigarettes consumed and mortality of any cause was seen. Therefore, it is not only if you smoke, it is also important how much you smoke. Nevertheless, since this outcome was not assessed, we assume that risk was uniform. In addition, they classify as “never smokers” any persons with less of forty years that smoke cigarettes. Is possible that a person of thirty-eight years who smoke twenty cigarettes per day for twenty years could be classified like a “never smoker”? We doubt it.

Currently, the use of e-cigarettes is controversial. As Chen J et al states in their study (3), we should carefully interpret this idea of a substitution. There is a great quantity of information about the risks of conventional cigarettes in estimation models like MCDA (Multi Criteria Decision Analysis); in comparison of the e-cigarettes that are “new” products, with less users and long-term information. Therefore, the possible consequences would be less precise and suggest a lower risk. Besides this, the authors found that the use of e-cigarettes expose the users to 9 from the 12 significant hazards identified in the conventional cigarettes, which are more related to neoplastic and respiratory effects. In addition, the virulence increase of the methicillin-resistant Staphylococcus aureus (MRSA) strains exposed to the vapor of e-cigarettes has also been described in rat models of pneumonia (4). Do we want to promote their use, although we don´t truly know the potential hidden risks of these devices?
As noted above, future research about e-cigarettes as an alternative to cigarettes has to consider the known risks about this topic. Therefore, it would provide a valuable conclusion about this global health problem instead of a dangerous illusion.

References:
1. Levy D, Borland R, Lindblom E, Goniewicz M, Meza R, Holford T, et al. Potential deaths averted in USA by replacing cigarettes with e-cigarettes. Tob Control. 2017 Oct 2. pii: tobaccocontrol-2017-053759.
2. Müezzinler A, Mons U, Gellert C, Schöttker B, Jansen E, Kee F, et al. Smoking and All-cause Mortality in Older Adults: Results From the CHANCES Consortium. Am J Prev Med. 2015 Nov;49(5):e53-e63.
3. Chen J, Bullen C, Dirks K. A Comparative Health Risk Assessment of Electronic Cigarettes and Conventional Cigarettes. Int J Environ Res Public Health. 2017 Apr 5;14(4).11.
4. Hwang J, Lyes M, Sladewski K, Enany S, McEachern E, Mathew D, et al. Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. J Mol Med (Berl). 2016 Jun;94(6):667-79.