E-cigarette or vaping product use–associated lung injury (EVALI) is a severe pulmonary illness caused by using e-cigarettes or vaping products. In the United States, in 2018, an alarming 25% of youth adopted e-cigarettes, with the overall number being more than 13 million individuals. E-cigarette–related respiratory diseases have been reported since 2012, but EVALI diagnoses peaked in 2019. To prioritize regulation and research to deal with the EVALI epidemic, an American Thoracic Society workshop was convened in 2021, which pinned down the need to understand the main factors that lead to EVALI. This would help prevent future outbreaks and aid in effectively managing the epidemic. The workshop proceedings have been published in a recent article in the Annals of the American Thoracic Society.

Study: The E-cigarette or Vaping Product Use–Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report. Image Credit: FOTOGRIN / Shutterstock

Regulatory Needs and Public Health Initiatives to Manage EVALI

A biorepository and national case registry are needed to comprehensively study the overall burden of EVALI-vitamin E acetate (VEA) and related disease. This will also help identify the biological alterations and chemical constituents responsible for disease progression. Further, a dedicated EVALI EMR code and coding systems are required to document EVALI and related diseases accurately. The coding systems should collect information on e-liquid components and vaping products.

Establishments of product standards and FDA regulation of nicotine vaping products are critical to guarantee that harmful chemicals like VEA are not added to products commonly consumed by the general public. To ensure the safety of cannabinoids and other vaping products, additional federal and state regulatory frameworks are needed. Another important public health initiative is continued public education on the risks of vaping product use, especially in relation to harmful chemicals like VEA.

Clinical Initiatives to Manage EVALI

More extensive clinical training to evaluate patient exposures is required. This would ensure a thorough assessment of exposure to vaping products. Further, researchers could conduct an over-time study of EVALI patients to develop better treatment protocols and standardized diagnosis and to study long-term outcomes.

Consensus is required on the diagnostic criteria to define EVALI and therapeutic management algorithms. This is particularly important to update CDC guidelines that require the exclusion of COVID-19. 

Understanding the Mechanisms of EVALI

In addition to the initiatives mentioned above, the workshop identified many initiatives needed to further our understanding of EVALI and prevent a similar outbreak in the future. Accessible compound libraries and comparable toxicity data are required in order to study e-cigarette constituents and their mixtures. Adequate safety testing has not been conducted on several chemicals that are heated and inhaled in an aerosolized form. High- and mid-throughput assessments should be developed to assess the toxicity of e-cigarette aerosol constituents. Such toxicity assessment may help answer outstanding research questions, such as the role of VEA in systemic inflammation.

More research on detecting and evaluating biomarkers of nicotine exposure is needed to understand disease pathogenesis better. The research will also help gain insights into the heterogeneous effects of a wide array of products and the sensitivity of current biomarkers. The primary aerosol products in nicotine e-cigarettes could include acrolein, formaldehyde, glycolaldehyde, and acetaldehyde-releasing agents. In addition, Isoprene epoxide, butadiene, isoprene, and methacrolein are present in cannabinoid e-cigarettes.

It is essential to devise a strategy to regulate tetrahydrocannabinol (THC)-containing products; therefore, the existing governmental restrictions on studying these products should be relaxed. Under the Controlled Substances Act, the declassification of marijuana as a Schedule I substance and a waiver of restrictions around using Schedule I substances for research is essential to study THC and other cannabis-based compounds. The interaction of cannabinoids with carrier oils, like VEA, is of particular interest to researchers. Also of great interest is the acute and long-term effects of active compounds within cannabis products. Should the restrictions be relaxed, these questions could be effectively studied in animal models.

Conclusion

The EVALI workshop identified the urgent need for a national EVALI case registry and biorepository. Besides this, sustained campaigning on the risks of e-cigarette use and the need for physician education on post-screening documentation of e-cigarette exposure was deemed highly necessary. More research on harmful e-cigarette additives, the establishment of manufacturing standards, and the regulation of e-cigarettes could be crucial in effectively managing the EVALI epidemic.

An integrated multidisciplinary approach will be needed to address the leading causes of EVALI and prevent future epidemics. The initiatives outlined in the workshop are expected to require significant federal investment and regulatory policy changes. The reduced probability of future epidemics and improvement in public health will be driven by the extent of coordinated action taken by the regulatory agencies, researchers, and users of e-cigarettes. 



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