(A) In the panel on the left, cells of the lung are damaged by one chemical inhaled within e-cigarette aerosols. This cell damage leads to epithelial and endothelial cell necrosis (indicated by a yellow “X”). An alternative hypothesis is depicted on the right, in which inhalation of chemicals common in e-cigarette aerosols (propylene glycol, glycerin, nicotine, or THC) alters the inflammatory state of the lungs, including changing alveolar macrophages to a proinflammatory phenotype with the release of inflammatory cytokines (indicated by yellow circles), such that a second hit causes a pathologic inflammatory response. (B) The immune state of the lungs is known to be altered by the chronic, daily inhalation of e-cigarette aerosols. It is likely that vitamin E is directly cytotoxic to lung cells (indicated by a yellow “X”), leading to necrosis, neutrophil recruitment and activation resulting in collateral damage, and noncardiac pulmonary edema. Illustration credit: Rachel Davidowitz. H&E-stained lung tissues are from the UCSD Liebow Collection, 1974.