INDOMETHACIN MODIFICATION OF IMMEDIATE-TYPE IMMUNOLOGICAL AIRWAY RESPONSES IN ALLERGIC ASTHMATIC AND NON-ASTHMATIC SUBJECTS - EVIDENCE FOR ALTERED ARACHIDONIC-ACID METABOLISM IN ASTHMA

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Abstract
To examine the role of arachidonic acid metabolism in the modulation of immediate-type immunologic airway responses, the effects of indomethacin (50 mg every 6 h for 96 h) and placebo on responses to antigen inhalation challenge in allergic asthmatic human subjects and a group of nonasthmatic subjects with allergic rhinitis were compared. Sensitivity to antigen was determined for changes in 1 s 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. After indomethacin, nonasthmatic subjects had a significant increase in antigen sensitivity. Indomethacin had no effect on antigen sensitivity in asthmatic subjects as measured by 1 s 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. Products of arachidonic acid metabolism apparently participate in vivo in the modulation of airway responses to immediate-type immunologic stimuli. This participation differs in asthmatic and nonasthmatic subjects.