INFLAMMATION IN AIRWAY DISEASE

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Asthma is a common airways disease in which inflammation plays a central role in pathogenesis. While the association of asthma and atopy is well established, the mechanisms by which allergic inflammation results in asthma have yet to be fully defined. This proposal 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 (BAL) and of tissues obtained by bronchial biopsy. The kinetics of the allergic response of the airways will be examined from l hour to 2 weeks following challenge, and the interrelationship of inflammatory events including mediator release, cell recruitment, cytokine gene expression, appearance of cytokine products, and antibody production will be assessed. The recruitment, antigen specificity, and function of THl/TH2 lymphocyte populations, will be a particular focus of study. Finally, the effect of topical corticosteroids on airway function, inflammation, and the response to allergen challenge will be examined. These studies will yield insights into the relationship between allergic inflammation and asthma which can guide approaches to treatment.