The effects of indomethacin on refractoriness following exercise both with and without a bronchoconstrictor response
European Respiratory Journal
T Th he e e ef ff fe ec ct ts s o of f i in nd do om me et th ha ac ci in n o on n r re ef fr ra ac ct to or ri in ne es ss s f fo ol ll lo ow wi in ng g e ex xe er rc ci is se e b bo ot th h w wi it th h a an nd d w wi it th ho ou ut t a a b br ro on nc ch ho oc co on ns st tr ri ic ct to or r r re es sp po on ns se e ABSTRACT: Repeated exercise tests demonstrate refractoriness to the development of exercise-induced asthma (EIA). It is unclear whether it is the initial exercise per se or the
... ise per se or the resulting bronchoconstriction that causes the attenuated response to the second exercise challenge. This study was designed to determine whether the reported blocking of the refractory period by indomethacin requires a significant bronchoconstriction following the primary exercise challenge. Thirteen asthmatic teenagers (aged 12-16 yrs) were tested on four visits. Each visit included two 7 min treadmill exercise challenges at 80% maximum heart rate, separated by a 30 min rest. Conditions for the second exercise challenge (Ch2) were always thermoneutral (20-22°C and 25-35% relative humidity (RH); whilst challenge one (Ch1) was completed twice in thermoneutral and twice in warm-humid breathing conditions (33-35°C and 90-95% RH). A pretreatment for 3 days in a double-blind design with either placebo or indomethacin was completed. Forced expiratory volume in one second (FEV 1 ) was measured before and repeatedly following each challenge. The % fall in FEV 1 following Ch1 of the placebo thermoneutral trial was taken as reference. "Percent protection" at each visit was expressed as the decrease in EIA following Ch2, compared to reference. Warm-humid breathing reduced the EIA post Ch1 by 75%, whilst providing similar protection to thermoneutral conditions. Indomethacin had no significant effect on EIA after Ch1, but reduced "percent protection" for both warm-humid (from 67 to 16%) and thermoneutral (from 70 to 26%) conditions. The data indicate that inhibitory prostaglandins play a major role in EIA refractoriness and suggest that the release of these prostaglandins is initiated by some exercise factor, independent of the development of bronchoconstriction.