EFFECT OF INHALED PGE(2) ON EXERCISE-INDUCED BRONCHOCONSTRICTION IN ASTHMATIC SUBJECTS

Previous studies have suggested that the endogenous release of inhibit ory prostanoids limits the bronchoconstrictor response to repeated exe rcise. The aim of our study was to determine whether inhaled prostagla ndin (PG)E(2) attenuates exercise-induced bronchoconstriction or metha choline airway responsiveness in asthmatic subjects. Eight subjects wi th mild stable asthma and exercise bronchoconstriction were studied on 4 separate days, 48 h apart. Subjects inhaled PGE(2) or placebo in a randomized, crossover, double-blind fashion, 30 min prior to an exerci se challenge or a methacholine challenge. PGE(2) inhalation significan tly attenuated exercise bronchoconstriction. The mean maximal %fall in FEV(1) after exercise was 26% (SEM 3.7%) after placebo, and was 9.7% (SEM 2.7%) after PGE(2) (p < 0.001). PGE(2) also significantly reduced the duration of exercise bronchoconstriction (p = 0.034). However, PG E(2) did not significantly attenuate methacholine airway responsivenes s. The geometric mean methacholine provocative concentration causing a 20% fall in FEV(1) (PC20) was 0.77 (%SEM 1.48) after placebo day, and 1.41 (%SEM 2.20) after PGE(2) (p = 0.30). These results demonstrate t hat inhaled PGE(2) markedly attenuates exercise bronchoconstriction in asthmatic subjects and suggest that this effect is not occurring thro ugh functional antagonism of airway smooth muscle.