E-cigarette vaping associated acute lung injury (EVALI): state of science and future research needs

Abstract

“E-Cigarette (e-cig) Vaping-Associated Acute Lung Injury” (EVALI) has been linked to vitamin-E-acetate (VEA) and Δ-9-tetrahydrocannabinol (THC), due to their presence in patients’ e-cigs and biological samples. Lacking standardized methodologies for patients’ data collection and comprehensive physicochemical/toxicological studies using real-world-vapor exposures, very little data are available, thus the underlying pathophysiological mechanism of EVALI is still unknown. This review aims to provide a comprehensive and critical appraisal of existing literature on clinical/epidemiological features and physicochemical-toxicological characterization of vaping emissions associated with EVALI. The literature review of 161 medical case reports revealed that the predominant demographic pattern was healthy white male, adolescent, or young adult, vaping illicit/informal THC-containing e-cigs. The main histopathologic pattern consisted of diffuse alveolar damage with bilateral ground-glass-opacities at chest radiograph/CT, and increased number of macrophages or neutrophils and foamy-macrophages in the bronchoalveolar lavage. The chemical analysis of THC/VEA e-cig vapors showed a chemical difference between THC/VEA and the single THC or VEA. The chemical characterization of vapors from counterfeit THC-based e-cigs or in-house-prepared e-liquids using either cannabidiol (CBD), VEA, or medium-chain triglycerides (MCT), identified many toxicants, such as carbonyls, volatile organic compounds, terpenes, silicon compounds, hydrocarbons, heavy metals, pesticides and various industrial/manufacturing/automotive-related chemicals. There is very scarce published toxicological data on emissions from THC/VEA e-liquids. However, CBD, MCT, and VEA emissions exert varying degrees of cytotoxicity, inflammation, and lung damage, depending on puffing topography and cell line. Major knowledge gaps were identified, including the need for more systematic-standardized epidemiological surveys, comprehensive physicochemical characterization of real-world e-cig emissions, and mechanistic studies linking emission properties to specific toxicological outcomes.

Keywords:

• EVALI
• vitamin E acetate (VEA)
• Δ-9-tetrahydrocannabinol (THC)
• e-cigarettes
• vaping
• counterfeit cartridges
• pneumonia
• acute lung injury
• acute respiratory distress syndrome (ARDS)

Acknowledgments

The authors gratefully acknowledge all the past and present members of the Center for Nanotechnology and Nanotoxicology, Harvard T.H. Chan School of Public Health, including Jeff Rawson Ph.D., Post-doctoral Fellow from Prof. George M. Whitesides Laboratory, Department of Chemistry and Chemical Biology, Harvard University, for helpful discussions and comments; Professor Dhimiter Bello, Department of Public Health, UMass Lowell, and Professor Ilias Kavouras, Environmental, Occupational, and Geospatial Health Sciences, CUNY Graduate School of Public Health and Health Policy, for the internal review of the manuscript; the Editor in Chief and the anonymous peer-reviewers selected by the editor for their suggestions and comments that helped to improve the quality of this manuscript.

Declaration of interest

This review aims to provide a comprehensive and critical appraisal of existing literature on clinical/epidemiological features and physicochemical-toxicological characterization of vaping emissions associated with EVALI. The authors believe that highlighting the knowledge gaps in the current literature and the limitations in the e-cigs regulations is necessary for the development of new study designs and for the federal regulatory agencies in future decisions on the regulation of e-cigs or vaping products, to prevent future outbreaks.

Supplemental material

Supplemental material for this article is available online at https://doi.org/10.1080/10408444.2022.2082918.

Additional information

Funding

This review was made possible by the T32 Grant No. HL007118 from NIH. The authors have not participated in and do not anticipate participation in any legal, regulatory, or advocacy proceedings related to the contents of the paper.