Opinion: ECigIntelligence smells a rat in bad science on e-cigs and COVID-19

The COVID-19 pandemic has raised the public profile of medical research to a huge degree, and we have seen probably some of the best and worst science of recent times compressed into just a few months, not to mention outlandish claims by the likes of Donald Trump.

E-cigarette research has also had a wide spectrum of credibility since the devices were introduced in earnest about ten years ago – and the signs are that this variability is here to stay. This is despite the pressing need for the public to be properly informed on all aspects of public health in the wake of COVID-19, and indeed vaping and the virus have inevitably been the subject of connections, resulting recently in a paper slated as one of the worst of 2020 in tobacco harm reduction circles, “Association between youth smoking, electronic cigarette use, and COVID-19”.

This paper purported to show that vaping is linked to a substantially increased risk from the coronavirus among teenagers and young adults, but it has been taken to task for methodological errors and biological implausibility. Critics even set up a PubPeer thread to itemise the concerns and call for its retraction, and another peer review, “Bad data and bad conclusions will lead to bad policy”, says that the findings “are so suspect that any conclusions drawn from it cannot be relied on”.

Dubious research on COVID-19 and vaping follows rapidly on from the other major misreported issue, EVALI (e-cigarette or vaping product use associated lung injury), where regulated e-cigs have been wrongly blamed.


Unfounded links


A particular concern is that unfounded links have made their way into the most reputable journals, such as an editorial in Lancet Respiratory Medicine last month, “The EVALI outbreak and vaping in the COVID-19 era”, which in another PubPeer response is said to have implied that the EVALI outbreak and perhaps even COVID-19 can be caused by nicotine vaping (and also warned that Public Health England is wrong to recommend e-cigs as an option to quit smoking, which is an enduring tension among organisations).

These top level issues – COVID-19, EVALI, quitting smoking (and also youth use) – are joined by plenty of continuing bad science on potential toxicological and biological effects of e-cigs, which has dogged the products since their introduction and shows no sign of letting up.

A prime recent example is a paper with the long-winded title “E-cigarette or vaping product use-associated lung injury produced in an animal model from electronic cigarette vapor exposure without tetrahydrocannabinol or vitamin E oil”. In other words, the researchers went looking for EVALI without its known association with unregulated cannabis e-cigs and vitamin E acetate.

What they found, in a preliminary report, is that an EVALI‐like condition can be induced in rats after exposure to tobacco‐flavoured propylene glycol/vegetable glycerol, operated at a high power setting of 70W and heated with a nickel-chromium heating coil, without the addition of THC, vitamin E acetate, or indeed nicotine.


Helpless animals burnt by overheated fumes


Use of a stainless-steel coil in a previous device at either 60W or 70W did not cause respiratory effects, so it is possible that the nickel-chromium coil has some effect; but nothing was observed at the lower 60W setting and this short paper does not disclose what devices were used or whether conditions were realistic. There is no evidence that nickel-chromium devices now in widespread use have adverse health effects when used correctly.

The authors conclude only that “chemical composition of vapour, reactive oxygen species, and particle size may all play a role. Vaporisation of propylene glycol/vegetable glycerol at a higher temperature may also have contributed” (but they didn’t measure this).

The response of harm reduction advocate Clive Bates to this study on an email group was scathing: “We…jacked up the power on a device until the lungs of the helpless animals were burnt by the toxic fumes from overheated e-liquid undergoing pyrolysis. The animals, unlike humans, had no control over the device so they could not stop the searing pain we were inflicting on them by the simple expedient of stopping vaping or puffing differently. So we pushed on and brought them close to death and sometimes beyond and then cut out their lungs and had a good look at what we’d done by way of suffering and pain.”

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    This may be amusing (though not for the rats) and indeed the authors caution about the potential danger of operating e-cig units at high settings, but this study looks to step well over the mark of what is reasonable for simulating use in an animal model.


    How ‘rats’ became ‘people’


    There are many such studies, of course, and most are consigned to obscurity in the backwaters of academic journals. But this one, like a substantial number, was publicised in a press release, by the University of California, Irvine. And in a highly suspect write-up, the press release does not once refer to rats or even animals but merely “subjects” (and also quotes one of the researchers as linking e-cigs with COVID-19).

    In turn, the release was picked up by the media such as the UK’s Daily Mirror, which duly translated “subjects” into “people”. And so this artificial animal study, which was only preliminary, now lives on as an alarming warning about direct human experience.

    This is irresponsible at best. All the actors are at fault – the researchers for rushing out early results of a poor study; the publisher (Journal of the American Heart Association – which had to retract a study earlier this year concerning vaping and heart attacks); and the university for its press release.

    Animal studies have their place in e-cig research because data can be obtained much faster than in human studies. A review of rodent studies found a mixed picture of effects on a number of markers, and crucially that certain effects remain less severe than with cigarette smoke. Likewise, in vitro human and animal cell research have merits, but studies in human subjects are preferred by bodies tasked with assessing evidence.


    Genuine data gaps that need filling


    As usual, it’s the UK that has come up with a balanced view of risks. In its latest statement on the potential toxicological risks of e-cigs, the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT), an independent scientific committee that provides advice to the British government, has considered risks as they should be – in the context of products produced according to appropriate manufacturing standards and used as recommended, and as a replacement for cigarette smoking.

    The COT cautiously says e-cigs are likely to be associated with a reduction in overall risk of adverse health effects, although the magnitude of the decrease will depend on the effect in question. But the exhaustive review – hundreds of new papers were considered up to the cut-off of mid-2019 and 130 found relevant – reveals few concerns.

    Inevitably, data gaps include the general lack of long-term toxicity, but specifically the COT identifies exposure to flavouring chemicals (and their breakdown products) and possible effects of long-term inhaled nicotine as data gaps. It also notes a lack of evidence for non-nicotine e-cigs.

    Filling these and other gaps requires good science conducted in the context of realistic use of e-cigs by humans and certainly not in the febrile atmosphere of the COVID-19 pandemic.

    – Marc Beishon ECigIntelligence health correspondent

    Photo: Wikimedia Commons

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    Marc Beishon

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