Effects of enalapril and imidapril in the capsaicin cough challenge test and spirometry parameters in healthy volunteers

Background: Angiotensin-converting enzyme inhibitors are highly effective, welltolerated drugs, but are associated with respiratory adverse effects such as cough and wheezing. Objectives: In this double-blind, randomized, two-way crossover study, the effects of two angiotensin-converting enzyme inhibitors, enalapril and imidapril, in the capsaicin cough challenge test and spirometry parameters were investigated. Methods: The study involved two sequential 21-day periods separated by a 7-day washout period. In each period, volunteers received a once-daily oral dose of placebo during the first 7 days, imidapril 5 mg or enalapril 10 mg from days 8 to 14, and imidapril 10 mg or enalapril 20 mg from days 15 to 21. Cough challenge was performed at baseline and at the end of each week of treatment. Spirometry was performed before and immediately after the capsaicin challenge. Fourteen healthy subjects were enrolled, but one was withdrawn while taking enalapril due to dry cough. Results: Neither enalapril nor imidapril significantly altered the capsaicin cough threshold. A small but significant reduction in forced expiratory volume in 1 sec and forced vital capacity was demonstrated after treatment with enalapril (p = 0.017 and p = 0.018, respectively), but not with imidapril. Capsaicin cough challenge was not associated with bronchospasm. Conclusion: Studies in asthmatics are needed to assess the clinical relevance of these data.