UC Davis

E-cigarette or vaping product associated lung injury (EVALI) is a severe pulmonary illness, causing a rise in hospitalizations and deaths in 2019. Vitamin E acetate (VEA) became a chemical of interest as it was found in the bronchoalveolar fluid of EVALI patients and in illicit vaping devices for tetrahydrocannabinol (THC) as a cutting agent. Several studies have suggested a causative role for VEA in the genesis of EVALI. However, the mechanism(s) for the cause of EVALI is still unclear, as well as an explanation for predominance of male patients during the outbreak. To investigate, male and female C57 BL6/J mice were exposed to filtered air or VEA aerosol for 3 h/day for 3 or 10 days. Bronchoalveolar lavage fluid (BALF) analysis, histology, physiological measurements, and mRNA expression levels were analyzed in mice. VEA aerosol caused an increase in BALF protein, BALF neutrophils, and inflammatory chemokines, in mice exposed to VEA, compared to their respective sham controls. BALF analysis in male mice exposed for 10 days to VEA showed a significant increase in total cell numbers, macrophages, protein, and non-viable cells compared to female mice exposed to VEA for the same period of time. Histopathology demonstrated an increase in inflammation in all the lung regions following 10 days of VEA exposure. In summary, this study of progressive exposure of VEA resulted in a significant increase in inflammatory and cellular changes compared to control mice. Given the bronchoalveolar lavage fluid analysis with epidemiological data, these results suggest VEA may cause greater inflammation in males compared to females.