Electronic cigarette vapor exposure exaggerates the pro-inflammatory response during influenza A viral infection in human distal airway epithelium

Abstract

Electronic cigarettes or vaping products have been marketed as a safer alternative to smoking, but very little is known about the health effects in the human lung, particularly in the distal airways, a key site of airway obstruction and destruction in chronic obstructive pulmonary disease that is often exacerbated by viral infections. The aim of this study was to investigate the effects of electronic cigarette vapor (e-vapor) on human distal airway epithelial responses to influenza A virus (IAV) infection. We isolated primary small airway epithelial cells (SAECs) from donor lungs free of lung disease, and cultured them at air–liquid interface (ALI). To measure markers of epithelial injury such as integrity of epithelial barrier structure and function, we selected a regimen of non-toxic, barrier preserving e-vapor exposure of cultured cells to 15 puffs of e-vapor from a commercially available e-cigarette once per day for 3 days, prior to IAV infection. After 72 h of infection, media and cell lysates were collected to measure cytokines involved in inflammatory and antiviral responses. Pre-exposure to e-vapor with IAV infection, compared to IAV infection alone, significantly increased inflammatory and antiviral mediators including IL-8, CXCL10, IFN-beta, and MX1. Our results suggest that e-vapor exposure amplifies human distal airway pro-inflammatory response to IAV infection, independently of the severity of cell injury during viral infection.

Alveolar macrophages from EVALI patients and e-cigarette users: a story of shifting phenotype

“…While histologic changes also demonstrated increased inflammation and edema, those animals exposed to e-cigarette vapors had decreased survival suggesting this hyperactive immune response was mounted due to vaping exposure that led to detrimental immune pathology in the delicate lung [ 30 ]; the cascade suggests e-cigarette aerosols prime the subject for an excessive inflammatory response to viral infection. This was similarly reported in an in vitro model using e-cigarette extracts on human small airway epithelial cells [ 31 ]. In contrast, in our human study we did not see increased inflammatory proteins (e.g.…”

Chronic low‐level JUUL aerosol exposure causes pulmonary immunologic, transcriptomic, and proteomic changes

“…74 Moreover, symptoms of EVALI overlap with those of COVID-19. 75 Although there is controversy on whether e-cigarette use alters COVID-19 susceptibility or severity, 76 there is evidence that e-cigarette aerosol exposure augments the inflammatory response to other types of viral infection 77,78 and is some cases may exacerbate symptoms of EVALI. 79 Thus, it is possible that prior e-cigarette use predisposes select individuals to adverse pulmonary outcomes associated with co-exposures due to subtle but significant molecular and cellular changes in the pulmonary microenvironment.…”

Aerosolized nicotine from e-cigarettes alters gene expression, increases lung protein permeability, and impairs viral clearance in murine influenza infection

“…Exposure to e-cigarette aerosols increased the infectivity of SARS-CoV-2 in a bronchial epithelial cell line ( 57 , 58 ). E-cigarette aerosols amplified the pro-inflammatory response of distal airway epithelial cells to influenza virus ( 110 ). Mice infected with influenza virus had reduced survival and greater lung injury when exposed to e-cigarette aerosols ( 50 ).…”