Cyclooxygenase metabolites play a different role in ozone-induced pulmonary function decline in asthmatics compared to normals

Indomethacin has been used to demonstrate that cyclooxygenase (COX) metabol ites of arachidonic acid play a mechanistic role in ozone-induced spirometr ic decline in normals (Nm). Since the weight of evidence suggests that asth matics (Asth) do not differ substantially from Nm subjects in the magnitude of their spirometric response to ozone, we sought to determine whether COX metabolites play a similar role in the asthmatic response to ozone. Thirte en (n = 13) Asth and nine (n = 9) Nm volunteers were pretreated with indome thacin or placebo (3 days, 75 mg/day), then exposed for 2 h to 400 ppb ozon e or clean air while performing mild intermittent exercise (Vi(min) = 30 L/ min.). Baseline changes in spirometry (FVC, FEV1, FEF25, FEF50, FEF60p, FEF 75) and soluble markers of COX metabolism (prostaglandin [PG] F2-alpha) wer e measured from induced sputum samples. Results showed similar reductions i n FVC (Asth = 12%, Nm = 10%) and FEV1 (Asth = 13%, Nm = 11%) in Asth and Nm following ozone. Variables representing small-airways function demonstrate d the greatest ozone-induced decline in Asth (FEF75 = 25%). Indomethacin pr etreatment significantly attenuated ozone-induced decreases in FVC and FEV1 in Nm, but not in Asth. Marked attenuation of ozone-induced decrements in FEF75 and FEF60p was observed in Asth but not in Nm. PCF2-alpha levels were similar in both groups prior to ozone exposure with indomethacin (Asth = 6 5 pg/ml, Nm = 59 pg/ml), but postexposure levels in Asth were significantly elevated (118 pg/ml) compared to Nm (54 pg/ml). We conclude that COX metab olites, such as PCF2-alpha, play an important but different role in asthmat ics than normals with respect to ozone-induced pulmonary function decline. Specifically, COX metabolites contribute to restrictive-type changes in nor mals and obstructive-type changes in small airways in asthmatics.