RESOLUTION OF ACE-INHIBITOR COUGH - CHANGES IN SUBJECTIVE COUGH AND RESPONSES TO INHALED CAPSAICIN, INTRADERMAL BRADYKININ AND SUBSTANCE-P

1 In eight hypertensive patients with ACE inhibitor-induced cough the resolution of the cough was examined in a prospective observational st udy over 4 weeks duration. Resolution of cough was measured by visual analogue scales and questionnaire at baseline and days 3, 7, 14 and 28 . In addition changes in cough sensitivity to inhaled capsaicin, and s kin responses to bradykinin and substance-P were measured at the same time points. 2 All patients recorded significant subjective improvemen t in cough questionnaire scores for severity and night time waking, an d by visual analogue scales for severity and frequency of cough (all P < 0.0005 for trend from day 0-28). Significant changes in subjective measures were recorded by 3 to 7 days for most measures, but further r eductions were observed up to day 28 (all P < 0.01 day 28 vs day 0). 3 The sensitivity to inhaled capsaicin fell over the 28 days of study a fter stopping enalapril. The potency of capsaicin relative to day 0 wa s reduced to 0.25 (95% CI 0.07-0.87) by day 14, and to 0.20 (95% CI 0. 06-0.67) by 28 days. 4 After stopping enalapril there was a highly sig nificant reduction in wheal area produced by intradermal bradykinin, w ith the majority of the effect seen by day 3 (P < 0.0005). The wheal a rea to intradermal substance-P also declined with time after stopping enalapril, but significant changes were not observed until 14 days (P < 0.01). 5 Multiple regression analysis of the rates of decline for th e subjective and objective measures of cough showed significant associ ations between the response to inhaled capsaicin and the VAS scores fo r severity of cough (P = 0.005) and frequency of cough (P = 0.011). Ca psaicin response was not related significantly to the severity of coug h measured by self-administered questionnaire. 6 There was a significa nt association between bradykinin response and VAS scores for frequenc y of cough (P < 0.04) and severity of cough (P < 0.05), but not with c ough by questionnaire or the capsaicin response. The response to subst ance-P did not relate significantly to any of the measures of cough. 7 Cough caused by enalapril improved markedly by 14 days but took up to 28 days to resolve. It was associated with increased sensitivity to i nhaled capsaicin which decreased over 28 days, and which paralleled ch anges in subjective cough scores.