E-Cigarette Use Causes a Unique Innate Immune Response in the Lung Involving Increased Neutrophilic Activation and Altered Mucin Secretion.
Am J Respir Crit Care Med. 2017 Oct 20. Epub 2017 Oct 20. PMID: 29053025
RATIONALE: E-cigarettes have become increasingly popular and little is known about their potential adverse health effects.
OBJECTIVE: To determine the effects of e-cigarette use on the airways.
METHODS: Induced sputum samples from cigarette smokers, e-cigarette users, and non-smokers, 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 RESULTS: E-cigarette users exhibited significant increases in aldehyde-detoxification and oxidative stress related proteins associated with cigarette smoke comparing to non-smokers. The levels of innate defense proteins associated with Chronic obstructive pulmonary disease (COPD), 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- 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 sensitivity to PMA-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.
CONCLUSIONS: Together, our results indicate that e-cigarette use alters the profile of innate defense proteins in airway secretions, inducing both similar and unique changes relative to cigarette smoking. These data challenge the concept that e-cigarettes are a healthier alternative to cigarettes.