Further insight into how such estimates can influence decision-making on e-cigarette regulation was provided last week in a webinar produced by the Ontario Tobacco Research Unit, which can be viewed here: https://www.youtube.com/watch?v=lbijYlq0iNI
The results of this meeting were written up and submitted for publication to the journal European Addiction Research, where they were published in September 2014. (Nutt, DJ et al, Estimating the Harms of Nicotine-Containing Products Using the MCDA Approach)(i). The report included a nod to the inherent subjectivity of the results: “A limitation of this study is the lack of hard evidence for the harms of most products on most of the criteria.”
This product of the ad-hoc committee took on a life of its own after it was embedded in reports and other communications issued by Public Health England, beginning in 2015.(ii) (The same year that Public Health England had engaged one of the participants in the process to lead its tobacco control efforts).
Very quickly PHE's claim and the study behind it came under fire. The medical journal the Lancet criticized the methods and also the conflict of interest by some of the authors (who were connected to e-cigarette manufacturers): "The reliance by PHE on work that the authors themselves accept is methodologically weak, and which is made all the more perilous by the declared conflicts of interest surrounding its funding, raises serious questions not only about the conclusions of the PHE report, but also about the quality of the agency's peer review process." (E-cigarettes: Public Health England's evidence-based confusion)(iii).
Cardiovascular effects: In a 2020 review of the cardiovascular effects of e-cigarettes Nicholas Buchanan and colleagues (xiii) urged caution in drawing conclusions about the relative safety of e-cigarettes: "While the current but still limited literature suggests that e-cigarette use may lead to fewer negative cardiovascular effects than conventional cigarettes, our review supports that there is not sufficient data to conclusively make these resolutions."
Blood Flow: In a 2022 study, Poonam Rao and colleagues (xiv) showed that a wide range of e-cigarettes impaired blood flow (as measured by flow-mediated dilation) in much the same way and to the same degree as combustible cigarettes. E-cigarette aerosol, cigarette smoke and marijuana smoke all impaired blood flow to approximately the same degree. Repeated exposure of arteries to inhaled smoke or e-cigarettes aerosols over many years is a risk factor for developing cardiovascular disease many years later. This study suggests that the cardiovascular disease risks from e-cigarette aerosol would not be less than from cigarette smoke.
Some scientists maintain that it is not possible to arrive at a relative risk assessment at this time: "It doesn't make any sense for us to claim that we know that it's 95% safer than combustible cigarettes," says Thomas Eissenberg. "The fact is: we don't know whether e-cigarette use is as lethal as combustible cigarette use, less lethal than combustible cigarette use, or more lethal than combustible cigarette use."
These different product designs produce distinct types of harms. Last year, American researchers detailed their findings that the nature and the type of tissue injury inflicted by e-cigarettes are distinct from that caused by combustible cigarettes and concluded that "Comparing e-cigarettes with combustible cigarettes using the same readouts and endpoints may be misleading as the two exposures differ markedly in the nature of the injury they induce and the types of tissues they affect."(Keith, R et al. Cardiorespiratory and Immunologic Effects of Electronic Cigarettes):(xv)
More and more scientists, including those cited above, are engaged in research which allows us to to reach a state of our knowledge and to know whether the cat is either alive or dead, but not both. From their work to date, we know that there are many adverse short-term health effects that presage future chronic disease, chiefly circulatory and respiratory diseases, for continuing vapers. This allows us to know that vaping has some harms. Until more observations are available, there can be no certainty in a conclusion that vaping is more or less hazardous than smoking, nor by how much.
(xiii) Nicholas D Buchanan, Jacob A Grimmer, Vineeta Tanwar, Neill Schwieterman, Peter J Mohler, Loren E Wold, Cardiovascular risk of electronic cigarettes: a review of preclinical and clinical studies, Cardiovascular Research, Volume 116, Issue 1, 1 January 2020, Pages 40–50. https://doi.org/10.1093/cvr/cvz256.
(xiv) Poonam Rao, MBBS, Daniel D Han, BA, Kelly Tan, Leila Mohammadi, MD, PhD, Ronak Derakhshandeh, MSc, Mina Navabzadeh, PharmD, Natasha Goyal, MD, Matthew L Springer, PhD, Comparable Impairment of Vascular Endothelial Function by a Wide Range of Electronic Nicotine Delivery Devices, Nicotine & Tobacco Research, 2022;, ntac019, https://doi.org/10.1093/ntr/ntac019.
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| OTRU Webinar: The Population Impact of E-Cigarettes in Canada: A Simulation Model |
2013: The meeting that decided that e-cigarettes are "95% safer"
It was in July of 2013 that a dozen men met for a two-day workshop in London, England to exchange views on the various forms in which nicotine could be consumed and the harms that were associated with each of those products.At the end of this exercise, they quantified their assessment of a continuum of risk for the different products they discussed. In their collective view, cigarettes were the most harmful, followed by small cigars which they felt were only two-thirds as harmful. Third and fourth on the list were cigars and water pipe (at less than 14% the risk of cigarettes). At the least harmful end of this spectrum was pharmaceutical nicotine (the nicotine patch, gums and oral sprays), which they ranked slightly ahead of e-cigarettes and snus for which the risk in comparison with cigarettes was thought to be 5% and 4%.
2015 - 2022: the persistence of "95% less harmful" in the face of direct and indirect rebuttal.
Other criticisms followed. Some characterized the estimate as a "factoid" with an "unreliable provenance" (Eissenberg et al. Invalidity of an Oft-Cited Estimate of the Relative Harms of Electronic Cigarettes)(iv). Others warned that "non-factual based predictions of comparative safety, such as the ‘95% safer’ quantification, are not helpful for the risk estimation of e-cigarettes and should not be used when discussing or promoting e-cigarettes." (Burrowes et al, Human lungs are created to breathe clean air: the questionable quantification of vaping safety “95% less harmful”(v)
Subsequent scientific panels convened by other governments have directly and indirectly rejected the Public Health England position. Neither the Nutt et al paper nor the Public Health England conclusions are referenced in the 775- page report prepared for the FDA by the National Academies of Science, Engineering and Medicine, (vi) although the 5% estimate of relative harm was identified as being supported by many scientists (p. 634). Nor does the 122 page report of the European Commission's Scientific Committee on Health, Environmental and Emerging Risks (SCHEER)(vii) published last year reference the papers, in part because it was mandated to "focus only on
health impacts compared to non-smoking." A report commissioned by the government of Spain and first released in 2020 concluded that the "the claim that the risk of e-cigarette use is reduced by 95% compared to traditional cigarettes is unsustainable with current evidence." (Informe Sobre los cigarillos electronicos: situacion actual, evidencia disponible y regulacion, p. 11).(viii)
Nonetheless, the "95% less harmful" continues to influence discussions on vaping policies. When Health Canada met with Rights 4 Vapers last fall, (ix) one of the specific questions put to the officials was: 'Do
you agree with Public Health England’s view that vaping is
95% less harmful than smoking?' (Government representatives neither endorsed nor refuted the estimate). The New Zealand cabinet made the decision to legalize vaping products with "light touch" regulations after receiving advice that they were 95% less harmful.(x)
Tobacco companies continue to use "95% less harmful" in their disinformation campaigns, such as the current "Clear the Smoke" campaign, discussed here earlier. For example, Imperial Tobacco Canada said in a February 14, 2022 news release: "Public Health England has said that vapour products are 95 percent less harmful than cigarettes." (xi)
2014-2021: Accumulating research on risks
As mentioned in previous posts, evidence on the risks of e-cigarettes is steadily growing, with increased research examining the impact of e-cigarette aerosols on cell tissues and other bio-markers of damage.
Both individual studies and systematic reviews of this expanding evidence base have come to the conclusion that e-cigarettes cannot at this time be considered safer than cigarettes with respect to:
Respiratory health effects: Jeffrey Gotts and colleagues (xii), 2019: "We conclude that current knowledge of these effects is insufficient to determine whether the respiratory health effects of e-cigarette are less than those of combustible tobacco products."
Blood Flow: In a 2022 study, Poonam Rao and colleagues (xiv) showed that a wide range of e-cigarettes impaired blood flow (as measured by flow-mediated dilation) in much the same way and to the same degree as combustible cigarettes. E-cigarette aerosol, cigarette smoke and marijuana smoke all impaired blood flow to approximately the same degree. Repeated exposure of arteries to inhaled smoke or e-cigarettes aerosols over many years is a risk factor for developing cardiovascular disease many years later. This study suggests that the cardiovascular disease risks from e-cigarette aerosol would not be less than from cigarette smoke.
Quantifying the difference between apples and oranges
In reaching this conclusion they provided a useful overview of the ways in which e-cigarettes cause harm:
"First, avoiding combustion does not remove all noxious chemicals. Although e-cigarettes do not form high levels of strongly carcinogenic benzopyrenes and tobacco-specific nitrosamines, heating mixtures of nicotine and propylene glycol and vegetable glycerin (PG:VG) in e-cigarettes generates reactive carbonyls such as formaldehyde, acetaldehyde, and acrolein [11, 12, 13, 14], which have been variably linked to carcinogenesis,[15] cardiovascular injury [16, 17], and increased risk of cardiovascular disease [18]. The generation of carbonyls from e-cigarettes varies with use patterns, e-liquid ingredients, and operating conditions [19], and even though the extent of carbonyl generation by e-cigarettes is generally lower than by combustible cigarettes, daily carbonyl exposure from e-cigarettes could still exceed exposure limits [20]. Second, e-cigarette aerosols sporadically contain metals (Fe, Ni, Cu, Cr, Zn, Pb), generated by the heating coil [21], which could add to the toxicity of the aerosol. Third, like combustible cigarettes, e-cigarettes produce aerosols that contain fine and ultrafine particles [22], which can trigger cardiovascular events and promote the progression of pulmonary and cardiovascular disease [23]. Finally, a direct comparison of the relative toxicity of e-cigarettes and combustible cigarettes may not be entirely meaningful. Toxicity due to a chemical, drug, or exposure depends upon its dose. Therefore, even though per puff, e-cigarettes may generate lower levels of toxins; their toxicity may approach that of combustible cigarettes if the use of e-cigarettes (exposure/dose) is higher than that of combustible cigarettes. For instance, if e-cigarettes are half as harmful as combustible cigarettes, but are used twice as much, there would be little harm reduction by using e-cigarettes over combustible cigarettes. Therefore, for both e-cigarettes and combustible cigarettes, harm could be reduced only by reducing exposure. Here too, the relationship is not straightforward. The dose response relationship between smoking and ischemic heart disease, for instance, is non-linear. It shows that smoking just 3 cigarettes a day imparts 80% of the harm attributable to smoking 20–40 cigarettes per day [24]. In other words, 85–92% reduction in exposure results in only 20% harm reduction. Therefore, reducing toxin exposure by using e-cigarettes may not result in proportional harm reduction. Indeed, as discussed below, recent evidence suggests that even though e-cigarettes generate lower levels of toxins than combustible cigarettes, their use may be associated with significant cardiorespiratory injury as well as immune dysregulation."
2021: More attempts to put a number on the concept of relative harm
Despite these cautions, and in the face of conflicting estimates, changing product designs and uncertain science, a group of New Zealand researchers nevertheless recently set out to establish a numerical comparison of the risks of smoking and vaping. Their motivation for doing so was ensure that policy makers who were using simulation models to evaluate regulatory options had a numerical estimate of harm to use in these calculations. Their results (Wilson, N et al. Improving on estimates of the potential relative harm to health from using modern ENDS (vaping) compared to tobacco smoking)(xvi) were published last November.
These researchers used bio-marker studies to compare relative harm. They sought to establish equivalencies among e-cigarettes, combustible cigarettes, certain toxic emissions and their known relationship to certain diseases.
In order to reflect the newer designs of products, they looked only at studies based on data collected after 2017. They only found 4 studies that provided the range of data their methods required, and within these studies was a wide range of results. The nature of the exercise meant significant lacunae remained, leading the research team to acknowledged "a high level of uncertainty of the relative harm of ENDS [electronic nicotine delivery systems] use compared to smoking."
With these caveats, they nonetheless produced an overall estimate of relative harm, finding modern e-cigarettes had 33.2% the harm of cigarettes: "This analysis suggests that the use of modern ENDS devices (vaping) could be up to a third as harmful to health as smoking in a high-income country setting."
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| Wilson et al, 2021 |
Like Schrodinger's cat ?...
Is it logical to simultaneously state that "the long-term health effects of vaping are unknown" and also that "vaping is a (much) less harmful option than smoking".? The underlying contradiction in this paradox -- that the harms are at the same time both not known and are known to be less than a certain value -- is analogous to Schrodinger's boxed cat, which was famously held to be both alive and dead until an actual observation could establish its true state.
References
(i) Nutt D, J, Phillips L, D, Balfour D, Curran H, V, Dockrell M, Foulds J, Fagerstrom K, Letlape K, Milton A, Polosa R, Ramsey J, Sweanor D: Estimating the Harms of Nicotine-Containing Products Using the MCDA Approach. Eur Addict Res 2014;20:218-225. doi: 10.1159/000360220.
(ii) Public Health England. Vaping in England: evidence update. 2015.
(ii) Public Health England. Vaping in England: evidence update. 2015.
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/733022/Ecigarettes_an_evidence_update_A_report_commissioned_by_Public_Health_England_FINAL.pdf
(iii). The Lancet. E-cigarettes: Public Health England's evidence-based confusion. Editorial. August 2015.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00042-2/fulltext
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00042-2/fulltext
(iv) Thomas Eissenberg, Aruni Bhatnagar, Simon Chapman, Sven-Eric Jordt, Alan Shihadeh, and Eric K. Soule, 2020: Invalidity of an Oft-Cited Estimate of the Relative Harms of Electronic Cigarettes American Journal of Public Health 110, 161_162, https://doi.org/10.2105/AJPH.2019.305424.
(v) Burrowes et al, Human lungs are created to breathe clean air: the questionable quantification of vaping safety “95% less harmful”. New Zealand MJ. June 2020.
https://journal.nzma.org.nz/journal-articles/human-lungs-are-created-to-breathe-clean-air-the-questionable-quantification-of-vaping-safety-95-less-harmful
https://journal.nzma.org.nz/journal-articles/human-lungs-are-created-to-breathe-clean-air-the-questionable-quantification-of-vaping-safety-95-less-harmful
(vi) National Academies of Sciences, Engineering and Medicine. Public Health Consequences of E-Cigarettes (2018) https://www.nap.edu/catalog/24952/public-health-consequences-of-e-cigarettes
(vii) European Commission's Scientific Committee on Health, Environmental and Emerging Risks (SCHEER). Opinion on electronic cigarettes. 2021. https://ec.europa.eu/health/system/files/2021-04/scheer_o_017_0.pdf
(viii) Government of Spain. Direccion general de salud publica. Informe Sobre los cigarillos electronicos: situacion actual, evidencia disponible y regulacion, 2021 (revised 2022)
https://www.sanidad.gob.es/ciudadanos/proteccionSalud/tabaco/docs/InformeCigarrilloselectronicos.pdf
https://www.sanidad.gob.es/ciudadanos/proteccionSalud/tabaco/docs/InformeCigarrilloselectronicos.pdf
(ix) Health Canada and Rights4Vapers Webinar, “The Regulatory Process: How Vaping Regulations are Decided, Drafted and Developed” – December 2, 2021
https://www.canada.ca/en/health-canada/services/health-concerns/tobacco/meeting-summaries-tobacco-vaping-industry/rights4vapers-webinar-december-2-2021.html; webinar can be viewed at:
https://www.rights4vapers.com/it-was-historic-it-was-hotly-anticipated-it-was-the-must-see-event-of-the-fall/
(x) New Zealand Cabinet Social Policy Committee. Memo from Associate Minister of Health. Regulation of smokeless tobacco and nicotine-delivery products. https://www.health.govt.nz/system/files/documents/information-release/cabinet-paper-regulation-smokeless-tobacco-and-nicotine-delivery-products.pdf
(xi) Imperial Tobacco Canada. Let's clear the smoke. Press release. February 14, 2022. https://www.imperialtobaccocanada.com/group/sites/BAT_AXYKCM.nsf/vwPagesWebLive/DOCBMM84/$FILE/Vaping-Let%27s_clear_the_smoke.pdf?openelement.
(xii) Gotts J E, Jordt S, McConnell R, Tarran R. What are the respiratory effects of e-cigarettes? BMJ 2019; 366 :l5275 doi:10.1136/bmj.l5275.
(xii) Gotts J E, Jordt S, McConnell R, Tarran R. What are the respiratory effects of e-cigarettes? BMJ 2019; 366 :l5275 doi:10.1136/bmj.l5275.
(xiii) Nicholas D Buchanan, Jacob A Grimmer, Vineeta Tanwar, Neill Schwieterman, Peter J Mohler, Loren E Wold, Cardiovascular risk of electronic cigarettes: a review of preclinical and clinical studies, Cardiovascular Research, Volume 116, Issue 1, 1 January 2020, Pages 40–50. https://doi.org/10.1093/cvr/cvz256.
(xiv) Poonam Rao, MBBS, Daniel D Han, BA, Kelly Tan, Leila Mohammadi, MD, PhD, Ronak Derakhshandeh, MSc, Mina Navabzadeh, PharmD, Natasha Goyal, MD, Matthew L Springer, PhD, Comparable Impairment of Vascular Endothelial Function by a Wide Range of Electronic Nicotine Delivery Devices, Nicotine & Tobacco Research, 2022;, ntac019, https://doi.org/10.1093/ntr/ntac019.
(xv) Keith R, Bhatnagar A. Cardiorespiratory and Immunologic Effects of Electronic Cigarettes. Curr Addict Rep. 2021;8(2):336-346. doi:10.1007/s40429-021-00359-7
(xvi) Wilson, N., Summers, J.A., Ait Ouakrim, D. et al. Improving on estimates of the potential relative harm to health from using modern ENDS (vaping) compared to tobacco smoking. BMC Public Health 21, 2038 (2021). https://doi.org/10.1186/s12889-021-12103-x.
(xvi) Wilson, N., Summers, J.A., Ait Ouakrim, D. et al. Improving on estimates of the potential relative harm to health from using modern ENDS (vaping) compared to tobacco smoking. BMC Public Health 21, 2038 (2021). https://doi.org/10.1186/s12889-021-12103-x.
