Menthol in electronic cigarettes causes biophysical inhibition of pulmonary surfactant

With an increasing prevalence of electronic cigarette (e-cigarette) use, especially among youth, there is an urgent need to better understand the biological risks and pathophysiology of health conditions related to e-cigarettes. A majority of e-cigarette aero-sols are in the submicron size and would deposit in the alveolar region of the lung, where they must first interact with the en-dogenous pulmonary surfactant. To date, little is known whether e-cigarette aerosols have an adverse impact on the pulmonary surfactant. We have systematically studied the effect of individual e-cigarette ingredients on an animal-derived clinical surfactant preparation, bovine lipid extract surfactant, using a combination of biophysical and analytical techniques, including in vitro bio-physical simulations using constrained drop surfactometry, molecular imaging with atomic force microscopy, chemical assays using carbon nuclear magnetic resonance and circular dichroism, and in silico molecular dynamics simulations. All data collec-tively suggest that flavorings used in e-cigarettes, especially menthol, play a predominant role in inhibiting the biophysical func-tion of the surfactant. The mechanism of biophysical inhibition appears to involve menthol interactions with both phospholipids and hydrophobic proteins of the natural surfactant. These results provide novel insights into the understanding of the health impact of e-cigarettes and may contribute to better regulation of e-cigarette products.