AIRWAY SECRETION IN RECURRENT AIRWAY OBSTRUCTION

本项目的目的是量化复发性气道阻塞（RAO）马的气道分泌活性，探讨气道分泌物产生和积累增加的机制，并评估这种增加的功能意义。马的RAO模拟了在人类疾病中观察到的许多变化，如慢性哮喘、慢性支气管炎和器质性粉尘引起的气道疾病，在这些疾病中，持续的粘液过量产生是气道阻塞的重要组成部分。免疫化学、形态计量学、功能和体外方法将被用于鉴定受疾病影响的马与对照组相比，粘液/黏液样物质的产生、分泌和上皮内储存的时间变化，并评估任何此类变化的功能意义。此外，增加分泌的机制将通过评估中性粒细胞弹性酶和内毒素对气道分泌活性的影响来解决。我的一般假设是，马的RAO与黏液产生的持续增加有关，即使在明显的疾病缓解期间也会导致气道阻塞，上皮内储存的增加伴随着这种持续增加，炎症介质中性粒细胞弹性蛋白酶浓度的增加或对该介质的超敏反应有助于分泌活性的增加。

The goal of this project is to quantify airway secretory activity in horses with recurrent airway obstruction (RAO), to investigate mechanisms underlying increased production and accumulation of airway secretions, and to assess the functional significance of this increase. Equine RAO mimics many of the changes observed in human diseases, such as chronic asthma, chronic bronchitis, and organic dust-induced airway disease, in which persistent mucus overproduction is an important component of airway obstruction. Immunochemical, morphometric, functional, and in vitro methods will be utilized to identify temporal alterations in the production, secretion, and intraepithelial storage of mucus/mucus-like material in disease-affected horses versus controls, and to assess the functional significance of any such alterations. In addition, mechanisms of increased secretion will be addressed by evaluating the effect of neutrophil elastase and endotoxin on airway secretory activity. It is my general hypothesis that equine RAO is associated with a persistent increase in mucus production that contributes to airway obstruction even during periods of apparent disease remission, that increased intraepithelial storage accompanies this persistent increase, and that increased concentrations of the inflammatory mediator neutrophil elastase or a hypersensitivity to this mediator contributes to increased secretory activity.