Evidence for mast cell activation during exercise-induced bronchoconstriction

Abstract

Controversy remains about the causative mediators in the bronchoconstrictive response to exercise in asthma. This study examined whether mast cell activation is a feature of exercise-induced bronchoconstriction by measuring urinary metabolites of mast cell mediators. Twelve nonsmoking subjects with mild asthma and a history of exercise- induced bronchoconstriction exercised on a stationary bicycle ergometer for 5 min at 80% maximum work load. Pulmonary function was monitored and urine was collected before and 30 and 90 min after the provocation. The urinary concentrations of the mast cell markers 9α,11β-prostaglandin (PG)F2 and N(T)-methylhistamine, as well as leukotriene E4 (LTE4) were determined by immunoassay. Seven of the 12 subjects (responders) experienced bronchoconstriction (>15% fall in the forced expiratory volume in one second) following exercise, whereas the pulmonary function of the remaining five subjects (nonresponders) remained stable. The urinary excretion (mean±SE) of 9α,11β-PGF2 in the responders increased significantly compared with the nonresponders at 30 (77.1±14.4 versus 37.2±5.6; p<0.05) and 90 min (79.3±8.6 versus 40.4±8.5, p<0.05) after exercise challenge. The urinary excretion of N(T)-methylhistamine and LTE4 was not significantly different between the two groups at 30 or 90 min after exercise. The findings represent the first documentation of increased urinary levels of 9α,11β-prostaglandin F2 in adults following exercise challenge and provides clear evidence for mast cell activation during exercise-induced bronchoconstriction in asthmatics.