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Am J Respir Crit Care Med. 2018 Feb 15;197(4):492-501. doi: 10.1164/rccm.201708-1590OC.

E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving Increased Neutrophilic Activation and Altered Mucin Secretion.

Author information

1
1 Marsico Lung Institute.
2
2 Department of Pathology and Laboratory Medicine, and.
3
3 Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Abstract

RATIONALE:

E-cigarettes have become increasingly popular and little is known about their potential adverse health effects.

OBJECTIVES:

To determine the effects of e-cigarette use on the airways.

METHODS:

Induced 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 RESULTS:

E-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.

CONCLUSIONS:

Together, 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.

KEYWORDS:

NET; e-cigarette; lung; mucin; neutrophil

PMID:
29053025
PMCID:
PMC5821909
[Available on 2019-02-15]
DOI:
10.1164/rccm.201708-1590OC

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