• Boris Reidel, Giorgia Radicioni, Phillip W Clapp, Amina A Ford, Sabri Abdelwahab, Meghan E Rebuli, Prashamsha Haridass, Neil E Alexis, Ilona Jaspers, and Mehmet Kesimer.
• 1 Marsico Lung Institute.
• Am. J. Respir. Crit. Care Med. 2018 Feb 15; 197 (4): 492501492-501.

RationaleE-cigarettes have become increasingly popular and little is known about their potential adverse health effects.ObjectivesTo determine the effects of e-cigarette use on the airways.MethodsInduced sputum samples from cigarette smokers, e-cigarette users, and nonsmokers were analyzed by quantitative proteomics, and the total and individual concentrations of mucins MUC5AC and MUC5B were determined by light scattering/refractometry and labeled mass spectrometry, respectively. Neutrophil extracellular trap (NET) formation rates were also determined for the same groups.Measurements And Main ResultsE-cigarette users exhibited significant increases in aldehyde-detoxification and oxidative stress-related proteins associated with cigarette smoke compared with nonsmokers. The levels of innate defense proteins associated with chronic obstructive pulmonary disease, such as elastase and matrix metalloproteinase-9, were significantly elevated in e-cigarette users as well. E-cigarette users' sputum also uniquely exhibited significant increases in neutrophil granulocyte-related and NET-related proteins, such as myeloperoxidase, azurocidin, and protein-arginine deiminase 4, despite no significant elevation in neutrophil cell counts. Peripheral neutrophils from e-cigarette users showed increased susceptibility to phorbol 12-myristate 13-acetate-induced NETosis. Finally, a compositional change in the gel-forming building blocks of airway mucus (i.e., an elevated concentration of mucin MUC5AC) was observed in both cigarette smokers and e-cigarette users.ConclusionsTogether, our results indicate that e-cigarette use alters the profile of innate defense proteins in airway secretions, inducing similar and unique changes relative to cigarette smoking. These data challenge the concept that e-cigarettes are a healthier alternative to cigarettes.

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