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. 2018 Feb 15;197(4):492-501. doi: 10.1164/rccm.201708-1590OC.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid
  • Cross-Sectional Studies
  • Electronic Nicotine Delivery Systems*
  • Female
  • Humans
  • Immunity, Innate / immunology*
  • Lung / immunology*
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Mucins / biosynthesis
  • Mucins / immunology*
  • Neutrophil Activation / immunology*
  • Respiratory Mucosa / immunology
  • Smoking / immunology*
  • Sputum / immunology
  • Young Adult


  • Mucins