Comparative effects of a fixed combination of reproterol hydrochloride and disodium cromoglycate with each agent alone on antigen-induced airway responses in sheep

The purpose of this study was to compare the effectiveness of an eight day treatment with clinically relevant doses of a fixed combination of the beta(2) mimetic reproterol hydrochloride and disodium cromoglycate with each agent given alone against antigen-induced early (EAR) and late airway responses (LAR) as well as postantigen-induced airway hyperresponsiveness (AHR) in allergic sheep, Animals were treated in a randomized fashion with either the inhaled combination (n = 6), reproterol hydrochloride alone (n = 6), disodium cromoglycate alone (n = 6), or placebo (n = 8), Treatments (two puffs from a metered dose inhaler) were given three times a day for 7 days and once on the 8th day 1 h before airway challenge with Ascaris suum antigen. In the placebo trial, antigen challenge resulted in EAR and LAR as measured by increases in specific lung resistance; these changes were followed 24 h later by AHR to inhaled carbachol, With respect to the placebo trial, treatment with reproterol hydrochloride reduced the EAR (P<0.05) and blocked the LAR (P<0.05), but had no effect on the post-challenge AHR, Treatment with disodium cromoglycate also reduced the EAR (P<0.05), blocked the LAR (P<0.05), and blocked the post-antigen-induced AHR (P<0.05). Treatment with the fixed combination reduced the EAR (P<0.05), blocked the LAR (P<0.05), and blocked the post-antigen-induced AHR (P<0.05), Comparison of the different agents indicated that the fixed combination gave significantly increased protection against the EAR than either agent alone, gave slightly better (P<0.05) protection against the late response than cromolyn sodium and gave better protection against post-antigen-induced AHR than reproterol hydrochloride alone. These results suggest that a fixed combination of a beta(2)-mimetic and disodium cromoglycate provides some increased protection against antigen-induced airway responses when compared to either agent alone in a controlled laboratory setting. (C) 1998 Academic Press.