Response to McNeill et al criticism of the report we prepared for WHO and subsequent review paper in Circulation on ecigs

Just as I was leaving for vacation a few weeks ago, Ann McNeill, Jean-Francois Etter, Konstantinos Farsalinos, Peter Hajek, Jacques l e Housezec, and Hayden McRobbie published a blistering critique of the review of the scientific evidence on e-cigarettes that Rachel Grana, Neal Benowitz, and I prepared for the WHO last year and the subsequent peer reviewed review paper that we published in Circulation a few months later based on the WHO report (that included several important papers published after we delivered the report to WHO).
 
When I finally read the NcNeill critique when I returned, I was surprised at its harsh tone, but, in consultation with my coauthors, decided that nothing would be gained by responding.  Our work is available for all to read to judge whether we made a fair assessment of the evidence.
 
A few days ago, however, I received a copy of a detailed response to the McNeill et al paper prepared by David W Bareham, which I reproduce in full below. 
 
It is worth mentioning that the advice that he gives his patients who are using e-cigarettes as part of quit attempts is essentially the same as what we recommented in a Cardiology Patient Page published in the same issue of Circulation as the review paper.
 
Here is what he wrote:
 
Dear Ann
 
Very many thanks for you and your colleague’s critique of The WHO’S recent document on Electronic Cigarettes/Vapourisers.
 
I am a respiratory clinician with a great interest in this issue, and I would like to point out that, from the first, I DO refer people to the their local Smoking Cessation Services for support with quitting via use of an electronic cigarette, if: they have had multiple attempts via other evidence-based methods but failed; do not wish to try anymore via those methods; and if THEY raise the topic of quitting via an electronic cigarette. I will discuss the current evidence base with them: that there is some evidence that on an individual level at least, these devices can help. I do point out that, to maximise the health benefits, that they do need to fully quit, and point out that “dual use” will reduce those potential benefits i.e. they need to “switch”. I inform them that, in my opinion, it is inconceivable that an electronic cigarette is either: more harmful, as harmful or, in fact, probably anything like as harmful, as the combustible cigarette. There is no combustion, no tar and no C02. However, I would like to raise a few issues with you regarding what you and your colleagues state, and would welcome your responses, with interest.
 

1. You state in your introduction that “e-cigarettes potentially offer a much less harmful form of nicotine delivery”, which is of course absolutely true, after you first compare the toxicity profile of ENDS with the 70+ carcinogens we know are contained in tobacco smoke. You pick up also on the language that the WHO report uses, and argue that it exaggerates the risks (the statements from Robert West in the media about “alarmist” reactions I think reflects this standpoint). I would strongly argue that there is an interesting “flip side” to this point, however, in that some of the language used by pro-harm reduction advocates understates the potential risks. For example: Peter Hajek and John Britton were associated with a 2009 New Scientist review (which I can forward you, if you like) of these devices, that ASH England still cite in their references, that stated that:

 
Although it is clearly true there is no combustion, we do know that, via the thermal decomposition of solvents (e.g. PEG), that carcinogens and toxins are produced, and indeed the Kosmider et al paper (that M. Goniewicz was involved in as you will be aware) here http://ntr.oxfordjournals.org/content/early/2014/05/14/ntr.ntu078.full  demonstrated that some of the higher-wattage/variable output devices can produce some of these toxic and potentially harmful substances, in the same volumes as combustible cigarettes. Thus, the statement by ASH in their June 2014 document on Electronic Cigarettes here http://www.ash.org.uk/files/documents/ASH_715.pdf  is also understating the known situation when proclaiming that: “Electronic cigarettes, which deliver nicotine without the harmful toxins found in tobacco smoke, . . .”. This statement from ASH was also utilised in The Sunday Times here http://www.thesundaytimes.co.uk/sto/news/uk_news/Health/article1399409.ece  in the Spring of this year, and is currently utilised by Boots here http://www.webmd.boots.com/a-to-z-guides/electronic-cigarettes-faqs?page=2    to sell electronic cigarettes on behalf of Imperial Tobacco. A statement here http://www.bbc.co.uk/news/health-27161965 from Peter Hajek claims that, in the context of electronic cigarettes, the effects of nicotine are akin to those of caffeine, was broadcast to the public on BBC Breakfast. At the time, he made no reference at all to the full toxicity profile of the devices. However, conversely here http://www.bbc.co.uk/news/health-28554456  , he subsequently states that “"This is not the final list of risks, others may emerge”, which is in fact very appropriate.
 
Therefore, please will your group, and others including organisations associated, not publically understate what is currently known about the carcinogens and toxins in the vapours in these devices. I believe the language is chosen to encourage smokers to “switch”, which from the perspective of the individual smoker is admirable. However, I would strongly argue that much of the language chosen, because it can clearly be interpreted as meaning that the devices are safe, as they emit no toxins, is clearly erroneous and misleading to all potential populations, including non-smokers and youth. Public Health policy must surely consider effects on all populations of these devices: to not to do this would be negligent. 
 

2. Dr Farsalinos has informed me that he is concerned about the effect of temperature on solvents, and the demonstrated effect that increased temperature has on Propylene Glycol, for example, will produce carbonyls, as per the Kosmider et al link above. This effect was basically replicated by Hutzler et al here http://download.springer.com/static/pdf/713/art%253A10.1007%252Fs00204-014-1294-7.pdf?auth66=1410598378_e3f439fa9f894ede33beb009d31f02f2&ext=.pdf and so we know that when the temperature applied to the solvents approaches 150oC, we see an increase in this group of carcinogens and toxins. Dr Farsalinos’ concerns are, I believe, demonstrated here on You Tube, with a series of experiments he has very recently posted, demonstrating the various temperatures produced by different vaping topologies: http://www.youtube.com/watch?v=G60Z8Npl-Gw and http://www.youtube.com/watch?v=ek1XPGrdaE4 and http://www.youtube.com/watch?v=CMMpW-G4EXs and http://www.youtube.com/watch?v=dyLdCLu_r9w and here http://www.youtube.com/watch?v=AVDSU-EUdtM. Maybe these are some of the “risks” that Professor Hajek refers to?

 
In relation to the Kosmider et al paper, the correspondence contact, Maciej Goniewicz, here http://www.prweb.com/releases/2014/05/prweb11874918.htm stated that: “These results suggest that some types of electronic cigarettes might expose their users to the same or even higher levels of carcinogenic formaldehyde than tobacco smoke. Users of high-voltage e-cigarettes need to be warned about this increased risk of harmful effects,” Potential users also clearly need to be informed, so that they can make a fully informed choice as to whether they wish to use these devices. However, as above, some of the widely broadcast language being currently utilised does not reflect this important information. (Please note, the Kosmider et al paper is also cited here http://circ.ahajournals.org/content/early/2014/08/22/CIR.0000000000000107.full.pdf in the American Heart Association’s very recent statement on electronic cigarettes).
 

3. Lungs are significantly different from other organs! The relevance of this statement is reflected here, in a paper by May and Wigand:

 
Biodetoxification Systems: The Body vs. The Lungs
 
Foods and cosmetics are “filtered” by the body’s detoxification systems, whereas the lungs lack any detoxification system. Therefore, a chemical may be “safe” if applied or ingested because the body’s detoxification systems disarm the potential harm that it may cause. But the very same chemical may be dangerous if inhaled through the lungs, since the lungs lack the capacity to disarm the potential of this chemical to do harm. The fact that the substances that appear on the GRAS list are designated to be used in foods and cosmetics/toiletries is important because ingredients that are ingested have a unique and different effect on the body than ingredients that are pyrolyzed and then inhaled. The biochemical digestion process of the approved additives has multiple opportunities to be detoxified in the body’s biochemical systems through biotransformation and biodetoxification. In the lungs, on the other hand, these same chemical reactions do not occur. This is because unlike the lungs, the body, through its biochemical systems, is able to distinguish different types of toxic substances based on their “functional groups” (i.e., the complex molecular structure that is characteristic of each chemical). For example, the body will metabolize a molecular structure known as an “aliphatic chain” more efficiently than it will metabolize a more complex structure known as an “aromatic ring.” This is because the former structure comprises a straight chain of saturated chemical bonds, whereas the latter structure is a cyclical chain of unsaturated chemical bonds. The lungs, however, not only lack the discriminatory capacity possessed by the body’s detoxification system, even worse, the lungs lack any capacity to identify the molecular structure of a toxic substance. Whereas the body has a variety of detoxification processes that correspond to the various molecular structures found in toxic substances, the lungs have none.” (May and Wigand, 2005, “The Right to Choose: Why Governments Should Compel the Tobacco Industry To Disclose Their Ingredients”).
 
Your group is not mentioning, let alone emphasising to the public, the fact that Propylene Glycol, although seen as GRAS for many uses, is not currently GRAS as utilised in an electronic cigarette, when the solvent is vapourised at temperatures approaching and sometimes exceeding 150oC, and it’s subsequent production of carbonyls. Why do you, therefore, use the analogy of a nicotine inhalator with an electronic cigarette? Does an inhalator increase its potential for harm via the thermal decomposition of solvents, as the electronic cigarette has proven to do? The lungs have far less ability than other body organs/systems to disarm this increased potential harm, as above. This fact should be made aware to all populations, so that they can make an informed choice as to whether they could/should try these products.
 

4. You state that: “Reference to placement near ‘candy’ and ‘medicines’ similarly seems intended to create an emotional response and lacks reference to evidence on what the significance of such placement might be.” This statement is sophistry in action. An excellent example of what I mean is here http://time.com/2896962/electronic-cigarette-executives-get-schooled-in-senate-hearing/ and the statement most relevant is this:

 
“There is a legal principle that people are responsible for the natural and logical effects of what you do, and you know that you are reaching children.”
 
It is a totally logical thought process that by placing candy-flavoured e-juice next to candy/confectionary, children may be preferentially attracted to the former items: you all know that to be true. In my local “Trotters Traders” shop, the confectionary is directly next to the e-juices, with “Tutti Fruiti” being one example. I believe it is absolutely clear what is going on here, and what the intentions are, remembering that currently, it is only advisable for traders not to sell electronic cigarettes and their juices to under-18s. This recent Trading Standards literature http://www.tradingstandards.gov.uk/policy/policy-pressitem.cfm/newsid/1551 exemplifies how easy it is for the under-18s to get hold of these items, as I am sure you are aware of. 
 

5. Do we have evidence that flavours attract children to e-juices more than adults? Lorillard, manufacturers of “Blu”, have warnes parents that this may be the case here http://www.realparentsrealanswers.com/what-you-need-to-know-about-e-cigarettes-infographic/, and may in fact be basing this warning on evidence that they started to collect as long ago as 1978 here http://legacy.library.ucsf.edu/tid/otl76b00/pdf . This fact is pick up on here by 29 Attorney Generals in the USA here http://www.ag.ny.gov/pdfs/FINAL_AG_FDA_Comment_Re_Deeming_Regulations.pdf who argue strongly that:

 
“We urge the FDA to ban all characterizing flavors other than tobacco and menthol in newly deemed tobacco products.29 The primary basis for doing so is the protection of public health, particularly of youth. However, quite apart from these health benefits, a complete prohibition of characterizing flavors offers many advantages for enforcement. Consumers and manufacturers would have clarity and certainty. Enforcers would not have to make difficult determinations about whether a word, phrase, logo, or packaging connoted a flavor. Regulators would not face years of disputes, laboratory tests, and litigation about whether, regardless of the name, labeling, and marketing, a tobacco product’s flavor does or does not appeal to youth, or is substantially equivalent, misbranded, or adulterated.”
 
Moreover, here http://www.aacr.org/AdvocacyPolicy/GovernmentAffairs/Documents/AACR%20ASCO%20Comments%20on%20FDA%20Proposed%20Tobacco%20Deeming%20Rule-FINAL.pdf the AACR/ASCO strongly argue that:
 
“Flavored ENDS have proliferated, and a recent study reported that there are now 7,764 unique e-cigarette flavors on the market. We are concerned that, like flavored combustible tobacco products, flavored ENDS may appeal to youth and potentiate continued use of and addiction to these products. However, some experts believe that the availability of flavored ENDS may encourage adult smokers to switch from combustible products to ENDS, prevent youth who use flavored ENDS from transitioning to combustible products, and enhance the efficacy of ENDS as cessation aids. Today, there is no evidence for or against this, and the public health benefits of flavored ENDS are currently unknown. Therefore, priority should be placed on preventing youth from using these products. (my emphasis)”
 
It is, therefore, certainly not just The WHO that are urging caution on these devices, as again you appear to be erroneously arguing in your paper: many other organisations are also, with their statements being published prior to The WHO’s.    
 

6. You state that:

 
“Current use of e-cigarettes in non-smoking youth is very low and there is currently virtually no regular use in children who have never smoked or never used tobacco”
 
Do we currently know how many children are using these devices? The ASH England position on adolescent/child use of e-cigs, their current June 2014 Brief here http://ash.org.uk/files/documents/ASH_715.pdf states that:
 
“The number of children and young people regularly using electronic cigarettes remains very low and their use is almost entirely amongst those who are current or ex-smokers.1 This is a similar pattern to that found in jurisdictions such as the USA.5”
 
There is now also this July document here http://www.ash.org.uk/files/documents/ASH_891.pdf which cites and describes the same raw data as:
 
“YouGov survey. Total sample size was 2,178 children aged 11 to 18. Fieldwork was undertaken 21st - 28th March 2013.”
 
The Faculty of Public Health Policy Document on E-Cigs here http://www.fph.org.uk/uploads/UK%20Faculty%20of%20Public%20Health%20-%20Policy%20paper%20on%20electronic%20cigarettes%20-%20FINAL%2023%20JUNE%202014.pdf states regarding this data:
 
“While research carried out for Action on Smoking and Health suggests that there is no current compelling evidence to suggest that young people are using electronic cigarettes as a ‗gateway‘ to smoking, this situation could change rapidly. The latest data from Action on Smoking and Health, a March 2013 survey of children 11-18 years old showed that of 1428 children who had heard of electronic cigarettes, 1% had tried them but none reported continued use. However, these data are now old, and a new survey is urgently indicated.” (my emphasis).
 
My point is, and probably that also shared by the Faculty, is that there have been significant changes in the market for e-cigs since March 2013. This is excellently described and discussed here http://tobaccotactics.org/index.php/E-cigarettes by the Tobacco Control Research Group “Tobacco Tactics” Team at The University of Bath.
 

7. On this same topic, I note with interest the details of the APPG Briefing, as attached and kindly forwarded to me by Robert West. Even though Deborah Arnott was apparently present, this ASH evidence was not cited, but Professor Hughes’ data was. Was this because you acknowledge that the ASH data is outdated? Moreover, the APPG document claims that:

 
“From analysis of the constituents of e-cigarette vapour, e-cigarette use from popular brands can be expected to be at least 20 times safer (and probably considerably more so) than smoking tobacco cigarettes in terms of long-term health risks” and cites the paper Hajek P, Etter J-F, Benowitz N, McRobbie H (2014) Electronic cigarettes: review of use, content, safety, effects on smokers, and potential for harm and benefit. Addiction. In Press.”
 
It appears to have escaped many reader’s attention that the cut –off point for data analysis for this paper was February 2014. Therefore, several key papers e.g. Kosmider et al and Hutzler et al are not included in this review. This fact needs to be acknowledged by your Group.
 

8. The APPG document also states that, as basically you do in the WHO Critique paper, that:

 
“The vapour exhaled from e-cigarette users consists largely of water, and propylene glycol or glycerine and is highly unlikely to be harmful to bystanders; nicotine concentrations in exhaled vapour are too low to have pharmacological effects on bystanders” and that “ Exposure of bystanders to chemicals in e-cigarette vapour is not at levels that would be expected to cause health problems”
 
There have been further studies in this field published and discussed since June 2014. Here is one, for example: http://pubs.rsc.org/en/content/articlelanding/2014/em/c4em00415a#divAbstract which I attach in full above. Moreover, there is a further source of new evidence from another very recent opinion paper demonstrating similar results by Francis Offerman, which was apparently peer reviewed via the Indoor Air 2014 Conference in July this year in Hong Kong, as demonstrated by the following link: http://www.indoorair2014.org/images/Indoor_Air%20Book_final.pdf  “Chemical emissions from e-cigarettes: direct and indirect passive exposure” T11e:x4t560 HP1448 (on page 82). Please note also this very interesting discussion regarding this literature between Professor Stanton Glantz at UCSF, Dr K Farsalinos and Francis Offerman himself: http://tobacco.ucsf.edu/indoor-air-expert-publishes-risk-assessment-e-cigarettes. On the topic of nicotine, I further attach here a piece of research published very recently with regard to the potential dangers of third hand nicotine from Electronic Cigarettes, and their potential to form carcinogens – TSNAs - in the presence of other chemicals: http://ntr.oxfordjournals.org/content/early/2014/08/28/ntr.ntu152.full.pdf+html. The main contact for this research, Maciej Goniewicz, who as you know, is prolific in this area, and I further attach a supporting key paper cited in his research. So, as well as the position statements by both The WHO and the American Heart Association on the use of electronic cigarettes in public areas, there is further evidence and analysis to demonstrate potential harm, and therefore the need for precaution.
 

9. You state “Use of the language ‘marketing is back’ is polemic and has no place in an academic report.” There is ample evidence, utilised in the Courts in the USA in the 1990s, of the type and style of marketing ploys previously utilised by the Tobacco Industry from the 1950s here, as you know http://legacy.library.ucsf.edu/popular_documents/;jsessionid=05E4D9223E62ED58C8904E4E62FC6519.tobacco03 . These are now being replicated by both “independent” electronic cigarette companies and tobacco companies that manufacture electronic cigarettes. This evidence for comparison can be seen here http://tobaccotactics.org/index.php/E-cigarettes. There is nothing impassioned or controversial about the statement made by the WHO: it is well evidenced, and highly relevant in any academic report e.g. the U.S. Courts analysing the multi-faceted issue of electronic cigarettes.  
10. You state that:

“The advent of e-cigarettes on the market has been accompanied by a continued reduction in youth smoking prevalence”.
 
However, you ignore other alternative causes for this reduction. As McKee (2014) points out:
 
“E-cigarette advocates note that the changes in the USA have coincided with a fall in smoking prevalence but ignore the long-term downward trend, as well as the impact of austerity, given that smoking rates fell during the Cuban economic crisis in the 1990s only to increase when recovery came about (Franco et al. 2013) as well as evidence that alcohol consumption, which might be expected to behave similarly to tobacco, has fallen during the current economic crisis (Harhay et al. 2014, Bor et al. 2013).”
 

11. You state that:

 
“As long as e-cigarettes continue to deliver concentrations of chemicals similar to what has been shown in tests so far, an understanding of the toxicology of these chemicals indicates a risk to users much lower than from tobacco cigarettes”.
 
At the European Respiratory Society Conference this week, this abstract was reviewed, indicating evidence in experiments in mice that electronic cigarettes vapours can induce both asthma and emphysema: https://www.ersnetsecure.org/public/prg_congres.abstract?ww_i_presentation=70441, hence the Society’s precautionary stance on these devices.
  
David W Bareham BSc Hons (Physiotherapy) MSc (Pain Management).
Specialist Respiratory Physiotherapist
Lincolnshire Community Health Services NHS Trust
Locality Office
Louth County Hospital
Louth
LN11 0EU