Chronic Inhalation of E-Cigarette Vapor Containing Nicotine Disrupts Airway Barrier Function and Induces Systemic Inflammation and Multi-Organ Fibrosis in Mice.
Am J Physiol Regul Integr Comp Physiol. 2018 Jan 31. Epub 2018 Jan 31. PMID: 29384700
Laura E Crotty Alexander
BACKGROUND: Electronic (e)-cigarettes theoretically may be safer than conventional tobacco. However, our prior studies demonstrated direct adverse effects of e-cigarette vapor (EV) on airway cells, including decreased viability and function. We hypothesize that repetitive, chronic inhalation of EV will diminish airway barrier function, leading to inflammatory protein release into circulation, creating a systemic inflammatory state, ultimately leading to distant organ injury and dysfunction.
METHODS: C57BL/6 and CD-1 mice underwent nose-only EV exposure daily for 3-6 months, followed by cardiorenal physiologic testing. Primary human bronchial epithelial cells were grown at an air-liquid interface and exposed to EV for 15 minutes daily for 3-5 days prior to functional testing.
RESULTS: Daily inhalation of EV increased circulating pro-inflammatory and pro-fibrotic proteins in both C57BL/6 and CD-1 mice: the greatest increases observed were in angiopoietin-1 (31-fold), and EGF (25-fold). Pro-inflammatory responses were recapitulated by daily EV exposures in vitro of human airway epithelium, with EV epithelium secreting higher IL-8 in response to infection (227 vs 37 pg/mL, respectively; p<0.05). Chronic EV inhalation in vivo reduced renal filtration by 20% (p=0.017). Fibrosis, assessed by Masson's trichrome and Picrosirius red staining, was increased in EV kidneys (1.86-fold, C57BL/6; 3.2-fold, CD-1; p<0.05), heart (2.75-fold, C57BL/6 mice; p<0.05) and liver (1.77-fold in CD-1; p<0.0001). Gene expression changes demonstrated pro-fibrotic pathway activation. EV inhalation altered cardiovascular function, with decreased heart rate (p<0.01), and elevated blood pressure (p=0.016).
CONCLUSIONS: These data demonstrate that chronic inhalation of EV may lead to increased inflammation, organ damage, and cardiorenal and hepatic disease.