Background: Currently available over-thecounter\ncough remedies historically have been criticized\nfor lack of scientific evidence supporting their efficacy.\nAlthough the first-generation antihistamine diphenhydramine\nis classified as an antitussive by the United States\nFood and Drug Administration, to the authorsâ�� knowledge\nit has never been shown to inhibit cough reflex sensitivity\nin subjects with pathological cough. Objective: To evaluate\nthe effect of diphenhydramine on cough reflex sensitivity.\nSetting: Montefiore Medical Center, an academic medical\ncenter in New York City. Methods: Twenty two subjects\nwith acute viral upper respiratory tract infection (common\ncold) underwent cough reflex sensitivity measurement\nemploying capsaicin challenge on 3 separate days, 2 h\nafter ingesting single doses of study drug (to coincide with\npeak blood concentrations), administered in randomized,\ndouble-blind manner: a multicomponent syrup containing\ndiphenhydramine (25 mg), phenylephrine (10 mg), in a\nnatural cocoa formulation; dextromethorphan (30 mg)\nsyrup; and, placebo syrup. The standard endpoint of\ncough challenge was used: concentration of capsaicin\ninducing C5 coughs (C5). Main outcome measure: Effect\non cough reflex sensitivity (C5). Results: A significant\ndifference (p = 0.0024) was established among groups,\nwith pairwise analysis revealing a significant increase in\nmean log C5 (0.4 �± 0.55 (SD); p\\0.01) for the\ndiphenhydramine-containing medication versus placebo,\nbut not for dextromethorphan versus placebo. Conclusions:\nOur results provide the initial evidence of the\nability of diphenhydramine to inhibit cough reflex sensitivity\nin subjects with acute pathological cough. Timing\nof cough reflex sensitivity measurement may not have\nallowed demonstration of maximal antitussive effect of\ndextromethorphan.
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