Critical Review of “Background Paper on E-Cigarettes” Prepared for the World Health Organization by Grana, Benowitz, and Glantz.

Analytical Observation 1)

It has become apparent that many legislators and public health experts are relying on Background Paper On E-Cigarettes prepared for the World Health Organization by Rachel Grana, Neal Benowitz, and…

Whereas Stanton Glantz and his team do a fairly good job of assembling the current body of research for their report, they unfortunately replace the story their own data tell with their personal opinions on E-cigarettes; opinions not based at all on their own presented data.

To illustrate how the paper’s data and it’s conclusions are often at odds, VapeAwareMD has created this critical review showing side by side, the assertions made and the data presented. Not only will one quickly realize the conclusions are not actually supported by the data, but in fact their conclusions more often than not contradict the data.

The purpose of this post is to critique the objective ‘facts’ presented by the authors, and allow readers to draw their own conclusions. Quotes from the report have been indented and italicized, my own personal comments are written in regular text. Unless otherwise noted, citations refer to: Background Paper on E-Cigarettes (Electronic Nicotine Delivery Systems) by Rachel Grana, Neal Benowitz and Stanton Glantz.

Professor Stanton Glantz and his research team at the Center for Tobacco Control Research and Education at UCSF…

“Youth are rapidly adopting E-cigarettes” (page 2 line 4)

Youth are still trying tobacco at a rate of 25.9%, compared to the increase from 4.7% to 10% for E-cigarettes (CDC data). It is worth mentioning, the vast majority of young vapers began with tobacco, and the WHO paper reports an association with youth, and effectively using Vapor Devices to quit Tobacco. (Page 30 lines 23-25)

“High Levels of Dual Use” (page 2, line 6)

While any tobacco usage does indeed increase risk of death significantly, vapor devices are used principally by smokers as stated on page 29 lines 8-9, page 31 line 12, page 32 line 26, and page 33 line 17, of “Background Paper on E-cigarettes”. The paper goes on to report that

“reduction in cigarettes per day were observed in several of the clinical studies” (page 71 line 3)

and again on page 59 where he reports “89% (of vapers) decreased cigarettes per day by an average of 39%” and again on page 68 lines 16-21:

Fifty-seven percent of participants in the nicotine e-cigarette group reduced their cigarettes per day by ≥50% by 6months compared to 41% in the patch group (p=0.002) and 45% in the non-nicotine e-cigarette group (p=0.08). Those randomized to the nicotine patch group were less adherent to the treatment (46%) than the 16mg e-cigarette group (78%) and the no-nicotine e-cigarette group (82%). (Page 68 lines 16-21)

Tobacco in any amount kills, there’s no question, but on page 75 lines 10-11, The WHO paper reports dual users “would have a longer lifespan.”

“Youth who use E-cigarettes are heavier (not lighter) smokers; youth who use e-cigarettes are much less likely to have stopped smoking” (page 2 lines 7-8)

This statement is deliberately misleading, as it misrepresents cross sectional data as longitudinal data. The key distinction is, correlation does not entail causation! It is equally possible that heavier youth smokers, who are unable to quit, are turning to vapor devices as means of replacing their tobacco addiction.

“The temporal and causal relationships between e-cigarette use and smoking have not been determined”(page 2 line 10-11)

As is the case with most of conclusions presented in Background Paper on E-Cigarettes, unknowns are presented as facts, and facts are ignored in arriving at conclusions; fortunately, at least the facts are reported:

“88% (of vapers) reported being “ex-smokers,” with an average of 9 quit attempts before using e-cigarettes. Two-thirds had tried previously to quit by using FDA approved cessation devices and 99% felt the e-cigarettes helped with quit attempt. (Page 32 lines 26-28)

{Aside from the remarkable result of 88% of the respondents actually reporting they had quit tobacco altogether, it is equally as impressive that 15% quit, even though they had not originally intended to.}

The WHO paper clearly reports the temporal and causal relationships between vapor devices and tobacco; Individuals begin with tobacco, the cause to switch to E-cigarettes is a desire to quit, and the inefficacy of traditional NRT products.

“E-cigarettes have not been proven to help people quit smoking”

Again, it is unclear as to how one arrives at this conclusion; from the WHO report itself:

22% of smokers (occasional and daily) at baseline had quit smoking at one-month, and 46% had quit at one year. (Page 31 lines 30-31)

31% (of vapers) reported they were not smoking tobacco cigarettes at the 6 month Survey time point. (Page 33 line 4)

42% (of vapers) reported that they achieved complete substitution in the first month of using the devices” (page 33, lines 30-31)

41% and 66% (of vapers) reported no conventional tobacco cigarette smoking at the time of survey” (page 33 line 19)

74% of respondents (vapers) who had used an e-cigarette reported not smoking for at least a few weeks.” (Page 33, lines 10-11)

It is possible that e-cigarettes even without nicotine act as substitutes for the sensory and behavioral effects of conventional cigarettes. (Page 70, lines 11-12)

73% of users started with intention to quit smoking and 88% reported being “ex-smokers,” with an average of 9 quit attempts before using e-cigarettes. Two-thirds had tried previously to quit by using FDA approved cessation devices and 99% felt the e-cigarettes helped with quit attempt. (Page 32 lines 26-28)

It is possible that e-cigarettes even without nicotine act as substitutes for the sensory and behavioral effects of conventional cigarettes. (page 70, lines 11-12)

The effectiveness of quitting with traditional NRT therapies is 7%; the data presented in the WHO paper indicates that vapor devices range from 314%-1257% more effective than traditional NRT therapy.

“E-cigarettes pollute the air less than conventional cigarettes, but they pollute the air” (page 2 line 29-30)

The WHO paper reports that vapor is primarily composed of well studied compounds generally regarded as safe by the FDA, and presents data showing the levels of detected potentially harmful compounds are in the range of outdoor urban air, and normal human breath.

“Aerosol in both nicotine and non-nicotine e-cigarettes was primarily compromised of propylene glycol and glycerol and flavoring agents” (page 43 lines 13-14.)

Both propylene glycol and glycerol have been granted GRAS (Generally Regarded As Safe) status by the FDA.

“The level of minor alkaloids in aerosol were below the limit of detection for both e-cigarettes” (page 40, lines 14-15)

“Table 3” (page 43) [showing levels of Volatile Organic Compounds (VOCs) in e-cigarettes that are undetectable, or on par with normal human exhalation and no detection of nicotine.]

In the original paper referenced by the WHO report, the author states the detected VOCs

“might be caused by the person in the chamber itself, because people are known to exhale formaldehyde in low amounts…the rising concentrations of acetic acid and acetone during e-cigarette operation may also be attributed to the metabolism of the consumer.” (T Shripp, 2012 page 28).

It should also be noted that most VOCs in tobacco are not detectable at any level in vapor, and even those that are found in both, tobacco VOCs are at levels approaching 6000% higher than vapor.

“People passively exposed to e-cigarettes aerosol absorb nicotine (measured as cotinine) with one study showing levels comparable to passive smokers” (Page 2 lines 30-31)

This study referenced in the paper by Flouris et al, is fundamentally flawed as it generates main stream using an air pump at unrealistic concentrations, and erroneously calls this

“second hand vapor” (page 62 line 13)

There is no side stream vapor with vapor devices, the only “2nd hand vapor” comes from human exhalation. 98% of nicotine from E-cigarettes is absorbed by the human lungs; an air pump is only capable of generating “main stream” vapor that has never passed through a primary users’ lungs, thus the study’s conclusions are fundamentally flawed and misleading.

The WHO report admits the study’s conditions:

“ are extremely high, {and} may not be realistic for indoor spaces” (page 62, line 16, page 64 line 6)

the WHO report also states there was no ventilation specified, which further supports the fact that the study conditions were unrealistic and do not reflect real world conditions. (page 62 10-11)

“There is little research on direct effects”

Though the studies Glantz et al present again follow the same pattern of taking data out of context and using it to mislead readers by injecting their own unsubstantiated conjecture, direct effects are irrelevant to a public use ban. “direct use” must be compared to direct use of tobacco cigarettes, which the scientific community widely agrees are much more harmful.

“Prohibit the use of e-cigarettes anywhere where the use of conventional cigarettes is prohibited”(page 3, line 8-9)

To follow this recommendation would take away the immense benefits as stated by Glantz et al and discussed above, based on nothing more than conjecture and supposition of potential future harm, and willful ignorance of data Glantz himself presents.

“The majority of e-cigarette users were cigarette smokers when they initiated e-cigarette use” (Page 33 line 16-17) and “the most common reason given to try e-cigarettes was to use them in places where smoking is restricted.”(Page 37 lines 28-29)

It is a utterly baffling how one can conclude that public use should be banned, when public use is a strong reason for adoption of a product that the WHO paper clearly demonstrates gets people off tobacco, and poses little to no risk to bystanders.

“Ban the use of characterizing flavors in E-cigarettes” (page 3 line 12)

The myriad of flavors is another aspect of vapor devices that draw smokers away from tobacco, and keeps them quit. To ban them, ostensibly because they appeal to children, sets a very dangerous precedent; are we also going to ban flavoring in soda or coffee because caffeine has potential for addiction?

“Prohibit claims that e-cigarettes are effective smoking cessation aids until such time as there is convincing scientific evidence that such claims are true for e-cigarettes as they are actually used in the general population.” (Page 3 lines 12-15)

If the future of a life saving device did not hang in the balance, this statement would actually be comical. The WHO paper provides no fewer than 8 scientific studies characterizing use in the general population, all of which showed quit rates at 314%-1257% the quit rate of approved NRT therapy.

Both sides of the debate can agree however, that strong quality control standards need to be put in place, and this is not a product that should be marketed to children; this however falls into the jurisdiction of the federal, not state government.

“Interest in the products has been increasing (Ayers et al., 2011) and an exponential rise in sales over the past 3 years (2010- 2013) has been due, at least in part, to widespread advertising via television commercials and print advertisements, that often feature celebrities, for the most popular brands” (page 6)

Vapor devices are a new product, and exponential growth is expected in any new product adoption curve; if you begin with a small number of initial users, the relative increase of users is exaggerated compared to the absolute increase of users. For example, if there is one user of a product, and they share it with 10 other people, you just experienced a “1000% increase in product adoption”, but an absolute gain of 10 users; if however you start with 1000 users, and gain the same absolute number of 10 users, it is only a 1% increase in product adoption. the fact that sales are growing exponentially are ostensibly more a reflection of the small initial group of users, than the effectiveness of advertising.

“In 2009, the WHO Study Group on Tobacco Product Regulation (TobReg) addressed the emerging regulatory issues pertaining to e-cigarettes. TobReg noted that there was very little published scientific evidence on the health effects of e-cigarettes, or their efficacy for smoking cessation (stated in TobReg Report 955)(World Health Organization, 2009) and that there was not sufficient evidence to support the cessation and health claims made by companies and those in the public health community who were advocating e-cigarettes for harm reduction.” (Page 6)

It’s been 5 years since this was published, and the WHO themselves have published an excellent body of research confirming that vapor devices are effective cessation and harm reduction tools in addition to the multitude of papers confirming the efficacy of this product.

“There is concern about potential health effects of chronic inhalation ofthe vaporized base components of the e-liquid.”(Page 15 lines 24-25)

This is statement is deliberately vague and misleading. Unfortunately to make the case against vapor devices, one must rely on these vague concerns over potential risk that are completely unsubstantiated, because the substantiated evidence indicates there is little to no harm as discussed throughout the WHO review paper.

“For example, claims that e-cigarettes are less harmful than cigarettes may encourage adoption by non-smokers (potentially children)” (page 17 lines 26-27)

Again, the WHO paper contradicts the general consensus of the scientific community that vapor devices are indeed less harmful than tobacco, and can only allude to potential future harm, because the actual data presented indicates:

“As with adult population-based studies, data suggest that e-cigarette use is most appealing and prevalent among youth who are also experimenting with or current users of tobacco cigarettes.” (Page 38 lines 18-20)

“3.2% of never smokers had tried an E-cigarette” (page 37, lines 7-8)

“1.1% current use among non-smokers or former smokers” (page 35 line 9)

The data presented on page 29 lines 8-9, page 31 line 12, page 32 line 26, page and 33 line 17, also confirm that this product is used principally by smokers and the rate of new user initiation is well below that of tobacco adoption or current use by both adults and youth.

“Whether the levels of toxicants in e-cigarette aerosol indicate an actual health risk compared to the nicotine inhaler is unknown, but toxic deliveries from both were far lower than from conventional cigarettes.” (Page 41, lines 23-25)

Again, Glantz et al treat an unknown as a fact, and ignores actual quantitative facts in arriving at their conclusion.

“Given these uncertainties, it is not clear to what extent the ultrafine particles delivered by e-cigarettes will have similar health effects and toxicity as ambient fine particles” (Page 46, lines 17-18)

In what appears to be a strained attempt to find something harmful about vapor, Glantz et all are essentially saying “they’re the same size particle as harmful compounds, so they might* be harmful.” Particle size alone does not mean a compound harmful any more than it means its beneficial. This is incredibly important to consider when taking into account that vapor particles are liquid, not solid state.

“Cytotoxicity was related to the concentration and number of flavorings used.(Page 50, lines 30-31)

In vitro analysis bears no relevance to the discussion of a public ban; if you pour alcohol on cells in a petri dish, they will die, if you pour vinegar on cells in a petri dish, they will die, if you pour lemon juice on cells in a petri dish they die; all of these are consumed regularly by humans.

“The thresholds for human toxicity of potential toxicants in e-cigarette aerosol are not known” (page 53 line 8-9)

Glantz et al are ignoring the propensity of the past 7 years of evidence, and at best can only raise questions regarding potential harm. 0 evidence has ever proved harm from propylene glycol or glycerin, (FDA GRAS compound) and the levels of VOCs and trace elements are in line with being in a close space with another human being, or outside in a large metro area.

“E-cigarette use, with or without nicotine, decreased some nicotine/tobacco abstinence withdrawal symptoms, including cigarette craving, although not to as great an extent as smoking a conventional cigarette.” (Page 54, lines 1-3)

This quote gives us some insight into why we see such phenomenal quit rates with vapor devices, and also clarifies the impact a ban would have on the public health. Smoking is an incredibly tough habit to break; making vaping as attractive as possible through allowing public may eclipse the perceived deficit in satisfaction from making the switch.

“The authors concluded that e-cigarettes deliver nicotine, can reduce withdrawal symptoms and appear have lower abuse potential compared to conventional cigarettes” (Page 60, lines 15-16)

The WHO paper again reports; vapor devices are an effective quitting tool, with low abuse potential.

“Active e-cigarette use and passive exposure to e-cigarette aerosol did not result in a statistically significant increase in these biomarkers over one hour of exposure. This study suggests that the increase in white cell count is mediated more by tobacco combustion products than by nicotine. (Page 63, lines 4-5)

The bio makers analyzed were white blood cells, and the WHO report again indicates that vapor devices and tobacco cigarettes have completely different health effects, and researchers have not been able to identify any negative health effects of “passive vaping.”

“As part of what appears to be a broad consensus in the UK that the introduction of e-cigarettes will reduce the harm of smoking, the anti-smoking advocacy group Action on Smoking and Health (ASH) UK has announced that it “does not consider it appropriate to include e-cigarettes under smokefree regulations” (page 84 lines 13-16)

This anti-smoking group has looked at the facts, and came to the conclusion that e-cigarettes pose no danger to bystanders, and are immensely helpful at ending the #1 preventable cause of death worldwide.

—- z-ref: adf2jguz

1) (03-2014) 'Critical Review of “Background Paper on E-Cigarettes” Prepared for the World Health Organization by Grana, Benowitz, and Glantz.', (Accessed 18 Mar., 2014).
research/documents/adf2jguz.txt · Last modified: 2014/03/28 16:33 by rainman