Indomethacin modification of immediate-type immunologic airway responses in allergic asthmatic and non-asthmatic subjects: evidence for altered arachidonic acid metabolism in asthma.
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.
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D001095:Arachidonic Acids / Q000276:immunology / Q000378:metabolism*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000378:metabolism / Q000494:pharmacology*; D008168:Lung / Q000503:physiopathology; D008176:Lung Volume Measurements; D008297:Male; D008688:Methacholine Compounds / Q000378:metabolism / Q000494:pharmacology; D010919:Placebos; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000378:metabolism
D001095:Arachidonic Acids; D008688:Methacholine Compounds; D010919:Placebos; D007213:Indomethacin