Background: Although inhaled corticosteroids are the most effective anti-inflammatory agents available for the treatment of asthma, they have, at best, only modest effects on airways responsiveness to methacholine. Thus, hyper-responsiveness to methacholine is a relatively insensitive monitor of the effectiveness of glucocorticoids in asthmatic subjects.
Objective: The study aimed to determine if airways hyper-responsiveness to bradykinin provides a more sensitive index of glucocorticoid responsiveness in asthmatic subjects than does hyper-responsiveness to methacholine.
Methods: A double-blind, placebo-controlled, parallel group study comparing the effects of inhaled fluticasone (220 micro g twice daily) on responsiveness to the two stimuli in asthmatic subjects who had never previously received corticosteroid therapy. Drug (n = 13) or placebo (n = 12) were administered for 16 weeks. Responsiveness to bradykinin and methacholine was determined at baseline and at 4 week intervals.
Results: Placebo did not alter responsiveness to either stimulus compared to baseline. Fluticasone treatment significantly reduced responsiveness to bradykinin (P < 0.001 by Friedman anova) and methacholine (P = 0.02), but changes in responsiveness to bradykinin were significantly greater than those in methacholine responsiveness (P = 0.002). Bradykinin responsiveness was decreased at all treatment times compared to baseline, while methacholine responsiveness was not decreased until 8 weeks of therapy. When data were analyzed as changes from baseline (DeltaLog PD20), DeltaLog PD20 for methacholine was not different at any time-point between the two treatment groups. By contrast, DeltaLog PD20 for bradykinin was significantly greater in patients receiving fluticasone compared to those on placebo at all but the 16-week treatment time. Ten of 13 subjects receiving fluticasone failed, on at least one post-treatment visit, to show a 20% fall in forced expiratory volume (FEV1), even at the highest dose of bradykinin.
Conclusions: Airways responsiveness to bradykinin is more profoundly, and more rapidly, reduced by inhaled glucocorticoids than is responsiveness to methacholine. Airways hyper-responsiveness to bradykinin provides a convenient and sensitive monitor of glucocorticoid responsiveness in asthma.