Effect of cigarette smoking on cough reflex induced by TRPV1 and TRPA1 stimulations

Background: Recent studies have shown that neurogenic inflammation induced by cigarette smoke is inhibited by TRPA1 antagonist, but not by TRPV1 antagonist. Since cough reflex sensitivity is known to be modified by smoking status, we investigated the effects of cigarette smoking on TRPA1- and TRPV1-induced cough and urge-to-cough in healthy males. Methods: Twenty-six healthy never-smokers and 30 healthy current smokers were recruited via public postings. Cough reflex thresholds and urge-to-cough were evaluated by inhalation of capsaicin, a TRPV1 agonist, and cinnamaldehyde, a TRPA1 agonist. The cough reflex thresholds were defined as the lowest concentrations of capsaicin and cinnamaldehyde that elicited two or more coughs (C ₂) and five or more coughs (C ₅), respectively. The urge-to-cough was evaluated using the modified Borg scale. Results: In capsaicin-induced cough, the cough reflex thresholds, as expressed by C ₂ and C ₅, in current smokers were significantly higher than those in never-smokers (p < 0.01 and p < 0.001, respectively). The urge-to-cough log-log slopes in current smokers were significantly lower than those of never-smokers (p < 0.001). There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. In cinnamaldehyde-induced cough, there were no significant differences in cough reflex thresholds in C ₂ and C ₅ between never-smokers and current smokers, nor were there any significant differences in urge-to-cough log-log slope between never-smokers and current smokers. There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. Conclusion: The study suggests that smoking has a differential effect on cough responses between TRPV1 and TRPA1 stimulations.