ASPIRIN-EVOKED SYNDROMES--SYSTEMATIC MAST CELL ACTIVATION AND ASTHMA

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This research addresses two clinical syndromes that are triggered by the ingestion of aspirin and other cyclooxygenase inhibitors. Aspirin-evoked asthma (AEM) is associated with bronchospasm, often severe, whereas aspirin-evoked systemic mastocyte activation (AEM) produces a syndrome of flushing, occasionally hypotension, and other consequences of the systemic release of mast cell mediators. The proposed studies on AEM will characterize the mediators released into the bronchoalveolar space following local challenge with aspirin. The biochemical and histologic responses of the upper airway to cyclooxygenase inhibition will be evaluated, and the hypothesis that a cyclooxygenase product restrains bronchoconstriction in patients with AEM will be selectively tested. In patients with-AEM, the preliminary observation that low doses of aspirin actually increase the release of the mast cell mediator, PGD2, will be examined in further studies. The question of whether either PGE2 or thromboxane A2 are the cyclooxygenase products that restrain mast cell mediator release will be examined, as will the consequences of cyclooxygenase inhibition on the morphology of cutaneous mast cells and their interactions with other cells. Integrated assessment of the biochemical, histological and functional response to aspirin in these two syndromes should provide new insights into their pathophysiology.