Urinary leukotriene E4 excretion in exercise-induced asthma

Recent evidence suggests that the cysteinyl-leukotrienes (LTC4, LTD4, and LTE4) may be important in the pathogenesis of exercise-induced asthma. To evaluate the role of these mediators further, nine asthmatic subjects with exercise-induced bronchoconstriction were studied on two occasions. On visit 1, subjects performed 6 min of treadmill exercise; the mean maximal percent fall in FEV1 was 38.0 +/- 5.3%. On visit 2, maximal bronchoconstriction observed after exercise was matched with aerosolized methacholine. Urine was collected in two 90-min fractions (0-90 and 90-180 min) after challenges and analyzed by high-performance liquid chromatography-radioimmunoassay for LTE4. There were no significant differences in urinary LTE4 excretion between exercise and methacholine challenges for the periods 0-90 min (16.9 +/- 5.4 vs. 20.4 +/- 4.2 ng/mmol urinary creatinine), 90-180 min (24.9 +/- 8.2 vs. 20.1 +/- 5.5), or 0-180 min (21.5 +/- 6.5 vs. 18.8 +/- 4.1). Thus in contrast to allergen-induced bronchoconstriction, there is little evidence for enhanced cysteinyl-leukotriene generation in exercise-induced bronchoconstriction as assessed by urinary LTE4. If local release and subsequent participation of functionally active cysteinyl-leukotrienes in the pathways that ultimately lead to bronchoconstriction after exercise challenge do occur, these are of insufficient magnitude to perturb urinary LTE4 excretion.