Review: Effect of drugs on human cough reflex sensitivity to inhaled capsaicin

Capsaicin, the pungent extract of red pepper (capsicum), has gained widespread use as a research tool among clinical investigators, as it induces cough in humans in a safe [1], dose-dependent, and reproducible manner [2,3]. Capsaicin cough challenge in humans was first described in 1984 [4], and has since been used to evaluate the effect of numerous pharmacological agents on cough reflex sensitivity. Although many drugs have been shown to inhibit induced cough in the laboratory, others have failed to do so, including agents widely regarded as clinically effective antitussives.A United States National Library of Medicine (PubMed) search was performed in September, 2012 using the search terms “cough” and “capsaicin” limited to human studies published in English. The abstracts of the 328 articles meeting those search criteria were reviewed and 56 studies were identified in which capsaicin cough challenge was employed to assess the effect of a pharmacological intervention on cough reflex sensitivity. Studies in which a positive drug effect was demonstrated (n = 33) are listed in Table？ 1[5-37]; trials in which no effect was noted (n = 30) are summarized in Table？ 2[4,10,12,17-19,35,37-59]. In seven of these studies, multiple drugs and/or multiple subject groups were evaluated, resulting in both positive and negative results in terms of assessment of drug activity. As the purpose of this review was to assess drug trials in which a potential therapeutic (antitussive) effect of a drug was being evaluated, studies demonstrating enhancement of cough reflex sensitivity by angiotensin-converting enzyme (ACE) inhibitors or other agents were excluded.This review has identified 33 studies in which a pharmacological intervention was demonstrated to inhibit cough reflex sensitivity to inhaled capsaicin in a variety of subject populations, thus supporting the role of cough challenge as a useful clinical tool in the evaluation of potential antitussives [3]. A striking difference betw