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Effect of e-Cigarette Use on Cough Reflex Sensitivity. BACKGROUND: E-cigarettes (e-cigs) have attained widespread popularity, yet knowledge of their physiologic effects remains minimal. The aim of this study was to evaluate the effect of a single exposure to e-cig vapor on cough reflex sensitivity. METHODS: Thirty healthy nonsmokers underwent cough reflex sensitivity measurement using capsaicin cough challenge at baseline, 15 min, and 24 h after e-cig exposure (30 puffs 30 s apart). The end point of cough challenge is the concentration of capsaicin inducing five or more coughs (C5). The number of coughs induced by each e-cig inhalation was counted. A subgroup of subjects (n = 8) subsequently underwent an identical protocol with a non-nicotine-containing e-cig. RESULTS: Cough reflex sensitivity was significantly inhibited (C5 increased) 15 min after e-cig use (?0.29; 95% CI, ?0.43 to ?0.15; P < .0001); 24 h later, C5 returned to baseline (0.24; 95% CI, 0.10-0.38; P = .0002 vs post-15-min value). A subgroup of eight subjects demonstrating the largest degree of cough reflex inhibition had no suppression after exposure to a non-nicotine-containing e-cig (P = .0078 for comparison of ?C5 after nicotine vs non-nicotine device). Furthermore, more coughing was induced by the nicotine-containing vs non-nicotine-containing device (P = .0156). CONCLUSIONS: A single session of e-cig use, approximating nicotine exposure of one tobacco cigarette, induces significant inhibition of cough reflex sensitivity. Exploratory analysis of a subgroup of subjects suggests that nicotine is responsible for this observation. Our data, consistent with previous studies of nicotine effect, suggest a dual action of nicotine: an immediate, peripheral protussive effect and a delayed central antitussive effect. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02203162; URL: www.clinicaltrials.gov.