TitleDose-Dependent Pulmonary Toxicity of Aerosolized Vitamin E Acetate.
Publication TypeJournal Article
Year of Publication2020
AuthorsMatsumoto, S, Fang, X, Traber, M, Jones, KD, Langelier, C, Serpa, PHayakawa, Calfee, CS, Matthay, MA, Gotts, JE
JournalAm J Respir Cell Mol Biol
Date Published08/2020
ISSN1535-4989
Abstract

E-cigarette, or vaping, product use-associated lung injury (EVALI) is a syndrome of acute respiratory failure characterized by monocytic and neutrophilic alveolar inflammation. Epidemiological and clinical evidence suggests a role of Vitamin E acetate (VEA) in the development of EVALI, yet it remains unclear whether VEA has direct pulmonary toxicity. To test the hypotheses that aerosolized VEA causes lung injury in mice and directly injures human alveolar epithelial cells, we exposed adult mice and primary human alveolar epithelial type II (AT II) cells to an aerosol of VEA generated by a device designed for vaping oils. Outcome measures in mice included lung edema, bronchoalveolar lavage (BAL) analysis, histology, and inflammatory cytokines; in vitro outcomes included cell death, cytokine release, cellular uptake of VEA, and gene expression analysis. Comparison exposures in both models included the popular nicotine-containing JUUL aerosol. We discovered that VEA caused dose-dependent increases in lung water and BAL protein compared to control and JUUL-exposed mice in association with increased BAL neutrophils, oil-laden macrophages, multinucleated giant cells, and inflammatory cytokines. VEA aerosol was also toxic to AT II cells, causing increased cell death and the release of monocyte and neutrophil chemokines. VEA was directly absorbed by AT II cells, resulting in the differential gene expression of several inflammatory biological pathways. Given the epidemiological and clinical characteristics of the EVALI outbreak, these results suggest that VEA plays an important causal role.

DOI10.1165/rcmb.2020-0209OC
Alternate JournalAm J Respir Cell Mol Biol
PubMed ID32822237
Grant ListU54 HL147127 / HL / NHLBI NIH HHS / United States