Indomethacin modification of immediate-type immunologic airway responses in allergic asthmatic and non-asthmatic subjects: evidence for altered arachidonic acid metabolism in asthma

Abstract

To examine the role of arachidonic acid metabolism in the modulation of immediate-type immunologic airway responses, we compared the effects of indomethacin (50 mg every 6 h for 96 h) and placebo on responses to antigen inhalation challenge in allergic asthmatic subjects and a group of nonasthmatic subjects with allergic rhinitis. Sensitivity to antigen was determined for changes in one-second forced expiratory volume, specific airway conductance, and expiratory flow at 25% of the forced vital capacity measured from partial flow-volume curves. The groups differed in terms of prechallenge pulmonary function and non-immunologic airway reactivity as determined by methacholine challenge, but were comparable with respect to intradermal sensitivity to ragweed antigen. After placebo, asthmatic subjects demonstrated approximately 3.5-fold greater sensitivity to antigen than that of nonasthmatic subjects. Indomethacin had no effect on prechallenge pulmonary function in either group. However, after indomethacin, non-asthmatic subjects had a significant increase in antigen sensitivity. Indomethacin had no effect on antigen sensitivity in asthmatic subjects as measured by one-second forced expiratory volume or expiratory flow at 25% of the forced vital capacity, and produced a slight but significant decrease as measured by specific airway conductance. Indomethacin failed to alter methacholine sensitivity in atopic, non-asthmatic subjects. These findings indicate that products of arachidonic acid metabolism participate in vivo in the modulation of airway responses to immediate-type immunologic stimuli, and that this participation differs in asthmatic and non-asthmatic subjects.