The outbreak of lung injuries often known as "EVALI" was nothing to do with nicotine vaping

Introduction . Many commentators, activists, academics and public health agencies continue to assert or imply that an outbreak of severe and fatal lung injuries that occurred primarily in the United States between mid-2019 and early 2020 may have been caused in part by nicotine vaping. This condition is often known as “EVALI” (E-cigarette, or Vaping, product use-Associated Lung Injury), a term coined by the US Centers For Disease Control and Prevention (CDC). Analysis . An examination of the evidence shows that EVALI cannot have been caused by nicotine vaping . The characteristics of the lung injury outbreak are consistent with localised supply chain contamination. The contaminant has been identified and is known to be Vitamin E Acetate. This had been used as a thickener or cutting agent in illicit Tetrahydrocannabinol (THC) cannabis vape pens. This agent cannot be mixed with nicotine vaping liquids and would serve no useful purpose if it could be. No other cause or causal agent has been identified that would both implicate nicotine liquids and be consistent with the geographical and temporal pattern of the lung injury outbreak. There is a vanishingly small chance that a second independent cause would be found in nicotine liquids, coinciding with the same geography, timing and symptoms as Vitamin E Acetate contamination of THC oils. Further, it is implausible that this hypothetical and currently unidentified cause would disappear in early 2020 without some remedial action in nicotine vaping products. But there has been no identifiable remedial action - nicotine vaping products have not changed, but EVALI has largely gone. Residual uncertainties are likely to be due to the unreliable testimony of users regarding their use of THC. Implications . The attribution of nicotine vaping as a cause of EVALI should stop. The term EVALI is misleading and should be retired and replaced. Risk communicators should shoulder their responsibility to correct residual false risk perceptions. There should be an objective inquiry into how EVALI was handled. Serious consideration should be given to the advantages of legalising and regulating cannabis products.


Introduction
The outbreak of lung injuries in the United States caused over 2,800 hospitalisations and the deaths of 68 mostly young people in the period between March 2019 and February 2020 (CDC). [1] The condition was initially given various labels (VAPI, VALI, VIPI), but CDC settled on E-cigarette, or Vaping, product use-Associated Lung Injury (EVALI) in guidance issued in October 2019. [2] The outbreak generated a large volume of commentary and news coverage about vaping, much of it confusing or misleading (Gartner et al. 2020) [3] and prompted political and regulatory overreactions ). [4] The responses of public health agencies and the media led to adverse changes in the perceptions of nicotine vaping risk in the United States (Dave et al. 2020). [5] There is evidence that EVALI-related communications questioning the safety of e-cigarettes led to an increase in combustible cigarette use (Katchmar et al. 2021). [6] Though the outbreak was almost entirely US-based, it affected risk perceptions beyond the US. For example, risk perceptions were adversely affected in the UK (Tattan-Birch et al. 2020) [7] , where the impact was picked up in annual ASH(UK) YouGov surveys as a negative step-change between 2019 and 2020 in smokers' perceptions of the harms of e-cigarettes (see chart below). [8] Smokers' changing perception of harm from e-cigarettes 2013-2021: Action on Smoking and Health (UK) / YouGov: reference [8].
Author's emphasis in red.
Qeios, CC-BY 4.0 · Article, July 26, 2021 Qeios ID: ZGVHM7.3 · https://doi.org/10.32388/ZGVHM7. 3 2 /10 In May 2021, the World Health Organisation's advisory group on the scientific basis for tobacco regulation issued a report with a chapter devoted to EVALI (Kheradmand & Crotty Alexander). [9]  February 2020 (CDC hospitalisation data -see the cover image for this paper) [1] . The EVALI outbreak is essentially over. It did not arise from THC or nicotine vaping products at scale before this period and largely disappeared after this period, though it is possible a few residual cases in 2020 were initially misdiagnosed as COVID-19 (CDC, 2020). [10] The outbreak was also limited in geography, primarily to North America. [11] This geographic and temporal pattern is consistent with a cause related to localised contaminated supply (comparable to a food poisoning outbreak). It means EVALI cannot be intrinsic to nicotine or THC vaping products because it would have been seen at other times and in other places, given nicotine vaping has been a worldwide phenomenon since around 2010. The US lung injury outbreak must have been caused by something about the products available in North America in the latter half of 2019.
2. The contaminating agent has been identified. It is Vitamin E Acetate (VEA) (Blount et al. 2020), [12] [13] which is used as a thickener or diluent in Tetrahydrocannabinol (THC) cannabis oils. Its exact biochemical interaction with lung tissue is uncertain and is a subject of ongoing work. [ December 2019) [16] 3. Vitamin E Acetate was added to illicit THC vapes as a thickener or 'cutting agent' to dilute the strength of expensive THC-containing oils while maintaining the viscosity of the liquid. THC users regard liquid viscosity as a mark of product potency and quality. The addition of VEA to THC vaping oils served an economic purpose, albeit a criminal and disreputable economic purpose. It is also possible that thickeners with similar chemical or physical properties to VEA could have a role, but none has been definitively identified so far, and attention has focussed exclusively on VEA. The supply chain involves 5. CDC data show that the EVALI cases had largely cleared up by early 2020 (see title chart above). [1] This is consistent with the North American illicit supply chain steadily emptying of VEA-contaminated THC products. It would be consistent with remedial action taken to address the risk in VEAcontaminated THC vapes by removing the VEA and using different thickeners or no thickeners. The criminal suppliers have strong incentives not to harm or kill their customers, not to increase their criminal liability, and not to degrade consumer confidence in their products. They will have removed VEA as soon as it became clear this was a causal agent in EVALI, probably starting in August 2019.
Arrests of illicit operators and closure of illicit suppliers will also have contributed to the decline, and these intensified from September 2019. [23] 6. No equivalent remedial action has been taken with nicotine vaping products. It has not been possible to identify any changes to e-liquid ingredients, devices or manufacturing processes for nicotine vaping products that would have ended their hypothetical role in causing EVALI. Such changes would need to address a speculative cause that remains unknown but is specific to the geography and timing of EVALI.
Yet, without any apparent change to nicotine vaping products, EVALI has declined to negligible levels.
The absence of any remedial actions reinforces the case that nicotine vaping products never had a role in EVALI. However, that does not justify extending the uncertainty to nicotine vaping for the reasons described in 1-7 above. The major sources of uncertainty are in the sporadic and ad hoc testing of EVALI patients for THC or VEA exposure and the poor reliability of users' accounts of their exposure. It is not surprising that some illicit THC users would deny illicit THC use -it could cause them difficulties (real or perceived) with their parents, school, college, employer, parole officer, or law enforcement. Some EVALI patients have initially denied using THC but changed their account in a more detailed follow-up interview (CDC, 2020). [24] Discordant reporting of cannabis use is common and well-documented (Palamar & Le, 2021) [25] and should be recognised as a limitation by investigators seeking causes of EVALI. This issue was highlighted by Dr. Scott Aberegg, a critical care pulmonologist at University of Utah Health. In a wry comment to CNBC, he stated: "It may turn out there are only two kinds of people who get this disease: those who vape THC and those who won't admit it". [26] The epidemiological approach described above is a more reliable way to assess the causes of the lung injury outbreak than user testimony.
9. Several theories have been advanced for how nicotine vapes could cause acute lung injury. With reference to Maddison et al. 2019, [27] Eissenberg & Maziak, 2020 [28] suggest exposure to lipids in eliquids may be a cause, though this is disputed. [29] Hayeck et al. 2020 [30] suggest a possible interaction between e-liquid solvents (PG and VG) and lung tissue surfactants. Kleinman et al.
2020 [31] suggested nickel alloys as a possible cause. This is not an exhaustive review, but these theories and the supporting early-stage research do not establish nicotine vaping as a cause of EVALI, and these results are subject to contested interpretations. More importantly, whatever their merits, these theories cannot explain the following: (1)  nothing to do with the EVALI outbreak. EVALI, as discussed above, can be explained convincingly and completely as a problem arising from sales of illicit THC vaping products containing oils that had been cut with Vitamin E Acetate. EVALI cannot be explained by the typical components, ingredients and production processes of nicotine vaping products.

Implications
Commentators should stop claiming that nicotine vaping is implicated in "EVALI" . Agencies, academics, journals, peer reviewers, health organisations, activist groups, foundations, media commentators, and politicians should stop falsely asserting or implying that nicotine vaping was a cause of EVALI. It is ethically inappropriate to use false or tenuous claims or exaggerated doubt about risks to try to change the behaviour of others. That ethical problem is compounded in this case because of the risk that users would be deterred from switching from high-risk to low-risk nicotine products and would therefore suffer harm based on misleading public health information.
"EVALI" should be renamed to reflect the real risks. The contrived naming of this condition as "Ecigarette, or Vaping, product use-Associated Lung Injury" (EVALI) is misleading, and the language is unnecessarily vague. Users and suppliers of THC vapes do not use the term "e-cigarettes" to describe THC vaping products such as vape pens. The term "e-cigarette" is primarily used to refer to nicotine vaping products that are replacements for cigarettes. [33] It follows that the term EVALI, by implicating ecigarettes, is misleading to nicotine users. At the same time, THC users are misled by an overly broad definition that seems to include all possible vaping products. But it is clear that the 2019 lung injury outbreak was attributable to a specific cause: Vitamin E Acetate added to THC vaping oils. A researcher who has called for renaming EVALI points out that we would not describe the opioid epidemic as an analgesic epidemic (Foulds, 2020). [34] A new effort should be made to define the best terminology to accurately communicate the nature of the risk to the right target audiences. Given that it coined the phrase EVALI, CDC should take responsibility for changing what has become unambiguously misleading terminology. There should be an inquiry into how EVALI was handled . It is not the purpose of this paper to assess or criticise the actions or intentions of anyone involved in the response to EVALI. However, it is important that lessons are learned and there is some accountability in public health. The handling of EVALI may go down as a public health failure, in which nicotine vapers were needlessly frightened away from a beneficial behaviour change, while THC vapers were given inadequately precise risk information. [35] Michael Siegel of the Department of Community Health Sciences, Boston University

Risk communicators should address
School of Public Health, provided a high quality and, at times, disturbing real-time commentary on the conduct of experts and agencies in responding to EVALI from August 2019 to January 2020. [36] The specialist Vaping 360 website has chronicled developments over this period and criticised the role played by CDC. [37][38] A more formal investigation, taking evidence from those directly involved, would be a fair and constructive way to identify and learn lessons from the handling of EVALI.
EVALI strengthens the case for the legalisation and regulation of cannabis products . The lung injury outbreak was caused by the reckless profit-seeking behaviour of actors in an illicit supply chain meeting ongoing demand for cannabis from millions of American consumers. Past 30-day cannabis prevalence among US 12th grade students (age 17-18) has been around 20 percent for 25 years, [39] with 11.8 million young adults reporting cannabis use in the past year (2018 data). [40] This high prevalence of use is despite the cannabis trade being illegal at the United States federal level and illegal at the individual state level for most or all of that period. [41] Prohibition does not prevent access to these products, it changes how such products are made available and who supplies them. Smith & Goniewicz 2021, [42] showed that odds of suffering EVALI were three times higher among users living in states with no legal access to cannabis compared to users in states with active recreational policies.
Compared to prohibition, the EVALI outbreak suggests it would be better for public health to have a regulatory regime that permitted cannabis products to be made available with acceptable safety standards while minimising risks from rogue producers. Such a regime could require, inter alia, the listing of ingredients, black-listing of hazardous additives, reporting and verification of psychoactive ingredients at known and predictable potency, appropriate warnings, and restrictions on retail availability, marketing and branding. European Union regulation prohibits the use of vitamins in nicotine vaping products [43] , though primarily to limit appeal rather than for safety reasons. This may have given some reassurance to nicotine vapers in the EU accessing legal nicotine products. [44][45] However, it would not stop rogue THC vape products from being sold illicitly and without any regulatory supervision.
Cannabis legalisation is a multi-faceted issue and cannot be justified or rejected just on the basis of the experience with EVALI alone. However, the experience of EVALI provides an additional consumer protection argument in favour of the legalisation and regulation of cannabis products.

Feedback and review
The author would welcome feedback and critical and constructive review of this analysis and will update it accordingly.