ROLE OF PULMONARY LEUKOSTASIS IN AIRWAY DYSFUNCTION

这项建议的目的是确定粒细胞的作用 聚集在肺功能障碍和支气管疾病发病机制中的作用 自发性可逆性呼吸道模型中的高反应性 小马上的障碍物。这种肺部疾病模型是独一无二的，因为 马科动物是唯一一种自发发展成周期性的家养动物 呼吸道阻塞，类似于人的哮喘，因为这种情况 以肺粒细胞聚集和呼吸道为特征 高反应性。这项建议的具体目标是：1. 慢性阻塞性肺疾病患者肺功能、气道反应性和粒细胞计数的相关性 缓解期间和治疗期间反复出现支气管梗阻的小马 支气管痉挛发作。2.测定粒细胞的作用 肺功能、气道反应性和肺功能衰竭 复发性支气管炎患者外周血中粒细胞的变化 缓解和暴露于干草尘之后。动态合规性， 肺阻力、强迫振荡电导、功能残留物 容量、血气压力和肺泡动脉氧分压 在意识清醒的小马身上测量，作为大小呼吸道的指示器 将生成组胺剂量-反应曲线，以评估 呼吸道反应性。开胸肺活检和定量形态检查将 用于测定呼吸道、间质和组织中的粒细胞浓度 肺血管系统。如果粒细胞被证明是重要的 呼吸道功能紊乱的发病机制，我们的长期目标是 探讨粒细胞产生肺损伤的机制 功能障碍。

The aim of this proposal is to determine the role of granulocyte aggregation in the pathogenesis of pulmonary dysfunction and bronchial hyperreactivity in a spontaneously occurring model of reversible airway obstruction in the pony. This model of lung disease is unique because equids are the only domestic animals which spontaneously develop recurrent airway obstruction, similar to asthma in persons and because the condition is characterized by both pulmonary granulocyte aggregation and airway hyperreactivity. The specific objectives of this proposal are: 1. To correlate pulmonary function, airway reactivity and granulocyte numbers in ponies with recurrent bronchial obstruction during remission and during attacks of bronchospasm. 2. To determine the effect of granulocyte depletion on pulmonary function, airway reactivity and pulmonary granulocyte numbers in ponies with recurrent bronchial obstruction during remission and following exposure to hay dust. Dynamic compliance, pulmonary resistance, forced oscillating conductance, functional residual capacity, blood gas tensions and alveolar arterial oxygen differences will be measured in conscious ponies as indicators of large and small airway caliber while histamine dose-response curves will be generated to assess airway reactivity. Open lung biopsies and quantitative morphology will be used to determine granulocyte concentrations in airways, interstitium and pulmonary vasculature. If granulocytes prove to be important in the pathogenesis of derangements in airway function, our long term goal is to investigate the mechanisms whereby granulocytes produce pulmonary dysfunction.