Comparative study of lung toxicity of E-cigarette ingredients to investigate E-cigarette or vaping product associated lung injury

Abstract

No comparative study has yet been performed on the respiratory effects of individual E-cigarette ingredients. Here, lung toxicity of individual ingredients of E-cigarette products containing nicotine or tetrahydrocannabinol was investigated. Mice were intratracheally administered propylene glycol (PG), vegetable glycerin (VG), vitamin E acetate (VEA), or nicotine individually for two weeks. Cytological and histological changes were noticed in PG- and VEA-treated mice that exhibited pathophysiological changes which were associated with symptoms seen in patients with symptoms of E-cigarette or Vaping Use-Associated Lung Injuries (EVALI) or E-cigarette users. Compared to potential human exposure situations, while the VEA exposure condition was similar to the dose equivalent of VEA content in E-cigarettes, the PG condition was about 47-137 times higher than the dose equivalent of the daily PG intake of E-cigarette users. These results reveal that VEA exposure is much more likely to cause problems related to EVALI in humans than PG. Transcriptomic analysis revealed that PG exposure was associated with fibrotic lung injury via the AKT signaling pathway and M2 macrophage polarization, and VEA exposure was associated with asthmatic airway inflammation via the mitogen-activated protein kinase signaling pathway. This study provides novel insights into the pathophysiological effects of individual ingredients of E-cigarettes.