Exercise is an important trigger of asthma. The underlying pathogenesis of exercise-induced asthma remains unclear. Heat loss or evaporative loss triggers ensuing events within the airways, although conflicting data exists about the relative importance of each factor. Recent evidence shows that exercise shares common pathophysiological features with other triggers for asthma including mediator release during the acute asthmatic response, the presence of a late airway response in many individuals, and the inhibition of the acute asthmatic response by therapies targeted at inflammatory mediators. Our hypothesis is that the pathogenesis of exercise-induced asthma is due to mediator, cytokine and chemokine release from mast cells and other airway cells during the early bronchoconstrictor response, which is followed by infiltration of the airways with inflammatory cells, during the late asthmatic response.
The specific aims are: 1) to define the nature of the cellular inflammatory response in the airways and peripheral blood during the development of the acute asthmatic response to exercise; 2) to determine if the late airway response to exercise results from infiltration of the airways by inflammatory cells; 3) to understand the relationship between the severity of preexistent airway inflammation and the development of a late airway response to exercise; 4) to determine the role of leukotriene antagonists and corticosteroids in the management of the late phase of exercise-induced asthma. The experimental approach will be to assess the release of specific mediators (histamine, tryptase, leukotrienes), Th2 cytokines (IL-3, IL-4, IL-5, IL-13), and eosinophil and neutrophil promoting chemokines (MCP-3, RANTES, eotoxin, IL-8) during the genesis of the acute asthmatic response to exercise. The late asthmatic response will be characterized by determining the composition of inflammatory cells (Eosinophils, Th2 lymphocytes, Neutrophils, Monocytes, Basophils), Th2 cytokines, eosinophil and neutrophil chemokines, and mediators (ECP, MBP, leukotrienes, histamine, tryptase) within the airways during the late asthmatic response to exercise. Elucidation of the mechanisms of exercise-induced asthma will be important in the development of new therapies for asthma.
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