Response to McKee and Capewell
Below is a response to the central assertions of McKee and Capewell's analysis  of Public Health England's (PHE) report  on e-cigarettes (EC).
1. McKee and Capewell: “ …reduced smoking (as opposed to quitting) may not reduce overall risk of death .”
RESPONSE: Meta-analyses and a systematic review show that reduced smoking improves outcomes [4,5].
Moreover, McKee and Capewell’s citation  derives from cohorts showing similar toxicant exposure among reducers and non-reducers, indicating compensatory inhalation . This would be expected without an alternate nicotine source. Conversely, dual users supplement their nicotine intake and should reduce their toxicant exposure per cigarette [7-9].
Indeed, EC interventions precede decreased CO and acrolein exposure among continuing smokers [10-13]. Additionally, dual use has already been shown to improve lung function [14,15] and pulmonary health [15,16].
While one cross-sectional study showed no reduced exposure among dual users , it measured only for weekly EC use (L Shahab, Personal communication). Furthermore, it cannot exclude longitudinal reductions.
2. McKee and Capewell: “The expression 'dual use'… rarely occurs in the PHE report”.
RESPONSE: Searching the report for the precise term “dual use” fails to uncover an entire section titled “Use of e-cigarettes while smoking” (cf. ).
3. McKee and Capewell: "Two thirds of EC users also smoke."
RESPONSE: Definitions are crucial: Smokers who occasionally vape and vapers who occasionally smoke are all ‘dual users’, yet their health risks are disparate. Most daily EC users don’t smoke regularly [19,20].
4. McKee and Capewell: “Dual use among daily 'vapers' apparently remained above 80% after 12 months follow-up.“
RESPONSE: PHE's report addresses this study, explaining that since only EC users who have failed to quit cigarettes were recruited, efficacy is invariably underestimated. Nevertheless, dedicated EC use while smoking strongly predicts future cessation [21,22].
Multi-year cohorts and randomized trials show that using nicotine replacements, smokeless tobacco or cessation drugs together with smoking increases future smoking cessation [23-29]. It is inconceivable that ECs promote the opposite.
5. McKee and Capewell: “The recent Cochrane review… concluded that the evidence was of 'low or very low quality by GRADE standards'.”
RESPONSE: The 'low' rating (downgraded from ‘moderate’) stems from the finding that the device in one trial delivers nicotine poorly, meaning effectiveness is underestimated. The 'very low' grade relates to the randomization against NRT, not absolute efficacy.
Furthermore, the GRADE ratings are relevant only to clinical trial results, but the Cochrane Review presents many other cogent lines of evidence .
Additionally, PHE’s conclusion that “recent studies support the Cochrane Review findings“ is entirely ignored.
6. McKee and Capewell: “The PHE report authors concede the weakness of the evidence, noting how a single observational study with substantial limitations offers 'some of the best evidence to date on the effectiveness of EC for use in quit attempts.'”
RESPONSE: These “substantial limitations” – namely, being “unable to explore prospective predictors of quitting, including pre-quit nicotine dependence”  – would, if anything, bias against a positive outcome (smokers switching to EC evidently being more dependent than those confident abstaining entirely). Though, the study went beyond adjustments typically undertaken, including controlling for pre-quit dependence indirectly .
7. McKee and Capewell: “… a recent systematic review, which the PHE report surprisingly fails to cite, came to a different conclusion.”
RESPONSE: The mentioned review largely neglects comparing toxicant levels to tobacco smoke, or even to consider the clinical significance of findings , while ignoring important systematic reviews which have successfully done so [33-35].
Moreover, its misrepresentation of almost every major issue in EC toxicology include the statements:
I. “Some studies found high maximum concentrations of total TSNA”, citing studies showing TSNAs 200-1,800 times below cigarette smoke levels [36-38].
II. “Exposure to formaldehyde was comparable with smoking", referring to a study calculating formaldehyde levels nine times below that from tobacco smoke .
III. “Propylene glycol has been found to exacerbate and/or induce multiple allergic symptoms in children”, citing a study stating that "apparently… outcomes were not driven by propylene glycol” .
IV. “Values below the threshold limit don't necessarily protect against the health effect of 200–300 daily inhalations over decades”, referring to safety limits calculated for 8 hours exposures “day after day, over a working lifetime” .
V. “These metals appear on the U.S. Food and Drug Administration's 'Harmful and Potentially Harmful Chemicals' list”, referring to metals detected below levels acceptable to the FDA for chronic inhalation [7,41-43].
8. McKee and Capewell attack the 95% estimate for "coming from" an analysis they dismiss on basis of limitations and conflicts of interests.
RESPONSE: This is surprising considering that PHE’s report independently assesses the toxicology, concluding that the figure "appears to remain a reasonable estimate" .
9. McKee and Capewell: “The authors categorically dismiss the possibility that e-cigarettes may be a gateway to smoking.”
RESPONSE: They do not . They explain that gateway terminology is “poorly defined”, suggesting its use be contingent upon a framework of how the theory can be tested. Tentative evidence that ECs divert youth away from smoking was also noted.
McKee and Capewell’s alleged “emerging evidence” for the gateway hypothesis uses methodology invalidated in PHE’s report.
10. McKee and Capewell: “The PHE report seems to equate lack of evidence with evidence of lack of effect. It claims that there is 'no identified risk to bystanders,' a view that may be premature.”
RESPONSE: Reporting "no identified risk" never precludes hypothetical discoveries. However, the report shows that continuous passive exposure levels are 1,000 times below active levels, the latter being below levels known to cause harm .
Exaggerating the harms of passive vaping likely damages public health, as outlined elsewhere .
11. McKee and Capewell: “… a consensus may be emerging: the English chief medical officer recently said that if EC have a role in smoking cessation that should be as 'licensed medicines.'”
RESPONSE: In reality, a wide range of experts contend that such policies may protect cigarette sales, as outlined in PHE's report [7,46-51].
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Competing interests: No competing interests