Asthma is a common airways disease in which inflammation plays a central role in pathogenesis. While the association of asthma is well established, the mechanisms by which allergic inflammation result in asthma have yet to be fully defined. This proosal will examine the biochemical and cellular mechanisms of inflammation in the model of segmental allergen challenge of the airways in allergic asthmatic subjects. Inflammation will be assessed by examination of cells and fluids obtained by bronchoalveolar lavage and of tissues obtained by bronchial biopsy. The kinetics of the allergic response of the airways will be examined from one hour to two weeks following challenge and the inter-relationship of inflammatory events including mediator release, cell recruitment, cytokine gene expression, appearance of cytokine products, and antibody production will be assessed. Recruitment, antigen specificity, and function of TH1/TH2 lymphocyte populations, will be a particular focus of the study. Finally, the effect of topical corticosteroids on airway function, inflammation, and the response to allergen challenge will be examined. These studies wil yield insights into the relatonship between allergic inflammation and asthma which can guide approaches to treatment.
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