Vaping and lung injury: No smoke without fire

E-cigarette use (generically “vaping”) is nothing if not controversial with respect to public health benefit.

Widely cited pluses are that vaping results in far lower exposure to the smoke, tar and carbon monoxide that make traditional coffin nails so dangerous, with the level of potential harm from vaping being close to that of nicotine replacement products of the patch, gum or spray variety. 

A 2018 report from Public Health England estimated that e-cigarettes were “95% less harmful” than regular cigarettes and were an aid to smoking cessation[1].

The European Public Health Association is not convinced when it comes to quantifying the relative safety of e-cigarettes (“statements that they are some percentage safer than conventional cigarettes are entirely unjustified”) and is more cautious over benefit in smoking cessation.[2] Expert authorities,  including the British Heart Foundation, recommend that non-smokers should not take up vaping[3].

Vaping has never been considered risk-free. Vaping products contain a variety of additives and solvents, including propylene glycol and glycerol: when heated, these give rise to known carcinogens and toxicants readily detectable in the urine of e-cigarette users[4]. And while vaping products may contain flavourings with a long history of safe use in the food industry, little is known about their toxic potential when heated and delivered to the lungs.

Uptake of vaping by otherwise non-smoking teenagers is of broad concern.  Teenage vapers might never adopt the less attractive smoking habits of their parents and older siblings, but there is apprehension that, despite an overall decline in tobacco use, a new generation of nicotine addicts is in the making.

The estimated 78% increase in e-cigarette use by American high school students in 2018 may prove to be a short-lived phenomenon driven by slick vaping technology and stealthy promotion, but it has prompted responses at state and federal level. A previous FDA Commissioner, Scott Gottlieb, described e-cigarette use as “an epidemic among teenagers[5], necessitating restrictions on the marketing of flavoured vaping products and tougher retail regulation[6].

The regulatory hammer now looks set to fall harder and faster with growing evidence for an association between potentially fatal lung injury and vaping, first reported in the US in August this year, and now designated as “e-cigarette, or vaping, product use associated lung injury (EVALI)” by the US Centers for Disease Control and Prevention in a newly-released interim guidance document[7]. At publication, 1,229 EVALI cases had been reported in the US or US territories, with 26 fatalities.[As of 22nd October, there were 1,604 reported EVALI cases and 34 deaths. Updates are available from the CDC website: http://tinyurl.com/y29saqdd]

Affected vapers, and their preferred products and vaping habits, are unlikely to be conveniently similar enough to easily pin down common causes of EVALI. Available data hints at a contribution from the tetrahedral cannabidiol (THC), with 76% of EVALI patients having used THC-containing products in the 90 days prior to onset of EVALI symptoms, and 32% using THC-containing products exclusively.  However, 58% reported use of nicotine-containing products, with 13% using nicotine-containing products exclusively, meaning that nicotine (or one of the many additives in vaping products) cannot be ruled out as either cause or contributor.[On November 5th, CDC announced that vitamin E acetate, often used to cut THC oil and as a thickening agent in vaping liquid, was detectable in lung fluid samples from EVALI patients. Although considered safe as a dietary supplement, vitamin E acetate is known to impair lung function  http://tinyurl.com/y29saqdd]

Analysis of lung biopsies by Mayo Clinic investigators found signs of acute lung injury in vapers consistent with chemical or toxic by-product damage, rather than suggestive of a rare form of pneumonia associated with the inhalation of oily substances (“exogenous lipoid pneumonia”)[8].

Several US states have been quick to respond to the heightened perception of serious risk from vaping, with Michigan, New York, California, Massachusetts and Rhode Island introducing outright bans or other controls on flavoured tobacco products last month[9]. India also announced an intention to ban vaping products, prompting the perhaps unfair observation that, in a country where the government is a major stakeholder in tobacco firms (and with some of the highest rates of smokeless tobacco use and oral cancer incidence in the world), public health might not be the only concern[10].

EVALI will undoubtedly precipitate widescale re-evaluation of vaping benefit versus harm, but this may only be the start of the vaping industry’s woes. A recent animal study suggests that chronic exposure to nicotine-containing e-cigarette smoke can give rise to potentially carcinogenic nitrosoamines, perhaps through chemical reaction with nitrosonium ions naturally present in mammalian cells, and result in higher rates of lung and bladder cancer than in unexposed animals.[11]

The relevance to real-life vaping product use and cancer risk awaits larger and more sophisticated investigation but the possibility exists that the carcinogenic potential of nicotine delivered via vaping is currently underestimated.

Photo credit: Lindsay Fox (Creative Commons Licence)

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[1] Evidence review of e-cigarettes and heated tobacco products. McNeill A et al. February 2018. http://tinyurl.com/ycake739

[2] Facts and fiction on e-cigs. European Public Health Association. August 2018. http://tinyurl.com/y4358wuj 

[3] Is vaping safe? Trevallion L. Heart Matters (British Heart Foundation blog) http://tinyurl.com/y3shysk4

[4] Adolescent exposure to toxic volatile organic chemicals from e-cigarettes. Pediatrics 2018: 141(4). Published online April 02, 2018 doi: 10.1542/peds.2017-3557

[5] Statement from FDA Commissioner Scott Gottlieb, M.D. on new steps to address epidemic of youth e-cigarette use . Press release online September 12^th 2018. http://tinyurl.com/y32z4yb2

[6] FDA considers regulatory action as vaping among US teens jumps 78% in a year. Dyer O. BMJ 2019;364:741 https://doi.org/10.1136/bmj.l741   Online February 14^th  2019.

[7] Update: Interim guidance for health care providers evaluating and caring for patients with suspected e-cigarette, or vaping, product use associated lung injury — United States, October 2019. Siegel DA et al. MMWR online October 11th, 2019. http://dx.doi.org/10.15585/mmwr.mm6841e3external icon 

[8] Pathology of vaping-associated lung injury. Butt YM et al. Correspondence, NEJM online 2^nd October 2019
https://www.nejm.org/doi/10.1056/NEJMc1913069 

[9] As the number of vaping-related deaths climbs, these states have implemented e-cigarette bans. Ducharme J Time Magazine online September 25^th 2019.  http://tinyurl.com/y573z8l7 

[10] India banned e-cigarettes — But beedis and chewing tobacco remain widespread. Frayer L and Pathak S. Goats and Soda. National Public Radio online 9^th October 2019 http://tinyurl.com/y5ltu3lo

[11] Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Tang M-S et al. PNAS online October 7^th 2019 https://doi.org/10.1073/pnas.1911321116