MECHANISMS OF AIRWAY INFLAMMATION IN ASPIRIN INTOLERANT ASTHMA

阿司匹林不耐受性哮喘（AIA）是一种影响5-10%哮喘人群的临床综合征。一类被称为环氧合酶（COX）抑制剂的药物，包括阿司匹林和吲哚美辛，刺激这些患者释放大量的半胱氨酸白三烯。肺部释放的半胱氨酸白三烯会导致哮喘症状和呼吸恶化。我们研究的总体目标是确定半胱氨酸白三烯是如何以及为什么在阿司匹林不耐受哮喘患者中释放的。我们正在利用支气管镜检查，研究与这种反应相关的肺化学物质和细胞的变化。支气管镜检查包括将一根薄的纤维管放入肺的大气道中，对肺组织和肺液进行小块取样。在我们的实验室里，对这些组织和液体进行分析，以检查选定的炎症细胞的活性，即肥大细胞和嗜酸性粒细胞。我们还测量了与炎症有关的化学物质的产生，包括脂质介质和细胞因子。迄今为止，我们已经证明COX抑制会导致半胱氨酸白三烯和15-HETE（一种在炎症中具有活性的脂质介质）的释放，以及肺部嗜酸性粒细胞的增加。这些发现将有助于确定半胱氨酸白三烯和其他脂质介质在哮喘中的重要性。

Aspirin-intolerant asthma (AIA) is a clinical syndrome affecting 5-10% of the asthmatic population. A class of medications called cyclooxygenase (COX) inhibitors, including aspirin and indomethacin, stimulates release of large quantities of cysteinyl leukotrienes in these patients. The cysteinyl leukotrienes released in the lungs causes worsening of asthma symptoms and breathing. The overall goal of our study is to determine how and why this release of cysteinyl leukotrienes occurs in patients with aspirin-intolerant asthma. We are studying changes in lung chemicals and cells that are associated with this reaction, utilizing bronchoscopy. Bronchoscopy involves placing a thin, fiberoptic tube into the large airways of the lung to sample small pieces of lung tissue and lung fluid. In our laboratory, this tissue and fluid is analyzed to examine activity of selected inflammatory cells, namely the mast cell and eosinophil. We also measure production of chemicals involved in inflammation, including lipid mediators and cytokines. To date, we have demonstrated that COX inhibition causes release of cysteinyl leukotrienes and 15-HETE (a lipid mediator with activity in inflammation), as well as an increase in eosinophils in the lungs. These findings will help determine the importance of cysteinyl leukotrienes and other lipid mediators in asthma.