It is well known that the prevalence of asthma is higher in athletes, such as Olympic athletes than in the general population.
In this study, we analyzed the mechanism of exercise-induced bronchoconstriction by using animal models of athlete asthma.
Mice were made to exercise on a treadmill for a total duration of 1 week, 3 weeks, or 5 weeks. We analyzed airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF), lung homogenates, and tissue histology at each duration. For mice that were treated, i.e., the treatment model, treatments were administered from the 4th to 5th week. We also collected the induced sputum from human athletes with asthma and their supernatant were analyzed.
AHR to methacholine was enhanced with repeated exercise stimulation, although cell composition in BALF did not change. Exercise-induced hypertrophy of airway smooth muscle and subepithelial collagen deposition. Cysteinyl-leukotrienes (cys-LTs) was significantly increased with exercise duration. Montelukast treatment significantly reduced AHR and airway remodeling. The expressions of phospholipase A2 group IV (PLA2G4) and leukotriene C4 synthase in the airway epithelium were upregulated in the exercise model, and the inhibition of PLA2 ameliorated AHR and airway remodeling with associated lower levels of cys-LTs. The levels of cys-LTs in the sputum of athletes were not different between athletes with and without sputum eosinophilia.
These data suggested that AHR and airway remodeling was caused by repeated and strenuous exercise. Cys-LTs from the airway epithelium but not inflammatory cells may play an important role in this mouse model.