title: 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 9alpha,11beta-prostaglandin (PG)F2 and Ntau-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 9alpha,11beta-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 Ntau-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 9alpha,11beta-prostaglandin F2 in adults following exercise challenge and provides clear evidence for mast cell activation during exercise-induced bronchoconstriction in asthmatics.
authors.affiliation: Experimental Asthma and Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: O'Sullivan
authors.forename: A
authors.initials: A
authors.lastname: Roquet
authors.forename: B
authors.initials: B
authors.lastname: Dahlén
authors.forename: F
authors.initials: F
authors.lastname: Larsen
authors.forename: A
authors.initials: A
authors.lastname: Eklund
authors.forename: M
authors.initials: M
authors.lastname: Kumlin
authors.forename: P M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: S E
authors.initials: SE
authors.lastname: Dahlén
mesh_terms: D000328:Adult; D001250:Asthma, Exercise-Induced / Q000503:physiopathology* / Q000652:urine; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000502:physiology; D015237:Dinoprost / Q000652:urine*; D005080:Exercise Test; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D008761:Methylhistamines / Q000652:urine*; D011863:Radioimmunoassay; D013997:Time Factors
chemical_list: D008761:Methylhistamines; D017999:Leukotriene E4; D015237:Dinoprost; C048140:N-methylhistamine