Electronic-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, 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 with 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.