Inflammatory phenotype modulation in the respiratory tract and systemic circulation of e-cigarette users: a pilot study

Am J Physiol Lung Cell Mol Physiol. 2021 Dec 1;321(6):L1134-L1146. doi: 10.1152/ajplung.00363.2021. Epub 2021 Oct 27.


Over 40 million people use e-cigarettes worldwide, but the impact of chronic e-cigarette use on health has not been adequately defined. In particular, effects of e-cigarette aerosol inhalation on inflammation and host defenses across the body are not fully understood. We conducted a longitudinal cohort pilot study to explore changes in the inflammatory state and monocyte function of e-cigarette users (n = 20) versus healthy controls (n = 13) and to evaluate effects of e-cigarette use reduction on the same. Saliva, sputum, and blood were obtained from e-cigarette users at baseline and after a 2-wk intervention of decreased e-cigarette use. Overall, across 38 proteins quantified by multiplex, airway samples from e-cigarette users tended to have decreased levels of immunomodulatory proteins relative to healthy controls, whereas levels of cytokines, chemokines, and growth factors in the circulation tended to be elevated. Specifically, e-cigarette users had lower levels of IL-1 receptor antagonist (IL-1Ra) in saliva (P < 0.0001), with higher IL-1Ra and growth-regulated oncogene (GRO) levels in sputum (P < 0.01 and P < 0.05, respectively), and higher levels of both TNFβ (P < 0.0001) and VEGF (P < 0.0001) in plasma. Circulating monocytes from e-cigarette users had alterations in their inflammatory phenotype in response to reduced e-cigarette use, with blunted IL-8 and IL-6 release upon challenge with bacterial lipopolysaccharide (P < 0.001 and P < 0.05, respectively), suggesting a decreased ability to appropriately respond to bacterial infection. Based on these findings, chronic inhalation of e-cigarette aerosols alters the inflammatory state of the airways and systemic circulation, raising concern for the development of both inflammatory and infectious diseases in chronic users of e-cigarettes.

Keywords: cytokine; e-cigarette; host defense; inflammation; monocyte.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Cytokines / analysis
  • Cytokines / metabolism*
  • Electronic Nicotine Delivery Systems / statistics & numerical data*
  • Female
  • Humans
  • Inflammation / chemically induced
  • Inflammation / diagnosis*
  • Inflammation / metabolism
  • Longitudinal Studies
  • Male
  • Pilot Projects
  • Plasma / drug effects
  • Plasma / metabolism
  • Respiratory System / drug effects
  • Respiratory System / immunology*
  • Respiratory System / metabolism
  • Respiratory System / pathology
  • Saliva / drug effects
  • Saliva / metabolism
  • Smoke / adverse effects*
  • Sputum / drug effects
  • Sputum / metabolism
  • Vaping / adverse effects*
  • Young Adult


  • Cytokines
  • Smoke