Airway immunopathology of asthma with exercise-induced bronchoconstriction

Background: Exercise-induced bronchoconstriction (EIB) is a common cause of symptoms in a subgroup of asthmatic subjects. The pathobiology that makes this group of asthmatic subjects susceptible to bronchoconstriction after a brief period of exercise remains poorly understood. Objective: We sought to determine whether there are differences in lower airway inflammation and production of cytokines and eicosanoids between asthmatic subjects with and without EIB. Methods: Two distinct groups of asthmatic subjects based on a priori definitions were identified, one with moderate-to-severe EIB and the other without significant bronchoconstriction after exercise challenge. Both groups met the definition of asthma on the basis of bronchodilator response, bronchial hyperresponsiveness, or both. A comparative immunopathology study was conducted by using induced sputum to identify differences in lower airway inflammation and production of cytokines and eicosanoids. Results: The groups had similar baseline lung function and bronchodilator response and did not have any asthma exacerbations within the prior year. The concentration of columnar epithelial cells was markedly higher in the group with EIB (1.4 X 10(5) vs 2.9 X 10(4) cells/mL, P = .01). The concentration of eosinophils was higher in the group with EIB (3.6 X 10(4) vs 4.9 X 10(3) cells/mL P = .04). Cysteinyl leukotrienes (CysLTs; 727.7 vs 151.9 pg/mL, P = .01) and the ratio of CysLTs to prostaglandin E-2 (1.85 vs 1.04, P = .002) in the airways were higher in the group with EIB. Conclusion: Injury to the airway epithelium, overexpression of CysLTs, relative underproduction of prostaglandin E2, and greater airway eosinophilia are distinctive immunopathologic features of asthma with EIB.