PATHOPHYSIOLOGY OF BRONCHIAL ASTHMA

支气管哮喘的病理生理学

• 批准号: 3336316
• 负责人: Adam Wanner
• 金额: $ 17.64万
• 依托单位: MOUNT SINAI MEDICAL CENTER (MIAMI BEACH)
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336316
• 关键词: Pasteurella; acetylcholine; airborne allergen; anaphylaxis; antihistamines; asthma; autoradiography; bacterial pneumonia; biological models; body fluid viscosity; bronchial mucus; bronchodilators; bronchoscopy; cilium /flagellum motility; disease /disorder model; histamine; ion transport; neurotransmitters; nonblood rheology; prostaglandins; radiotracer; respiratory airflow disorder; respiratory airflow measurement; respiratory airway clearance; respiratory airway pressure; respiratory airway volume; respiratory imaging /visualization; respiratory pharmacology; scanning electron microscopy; secretion; tissue /cell culture

Bronchial asthma is characterized by the triad of airway smooth muscle contraction, mucociliary dysfunction and edema. Two of these manifestations involve the mucosa. During the previous and current grant periods, we conducted a series of experiments in an attempt to characterized airway mucociliary function in a sheep model of allergic bronchoconstriction. Those studies have demonstrated that antigen challenge leads to an impairment of mucociliary clearance which is related to chemical mediators of anaphylaxis, is caused by abnormal airway secretory functions, and persists for several days. The overall objective of the present proposal is to extend those observations to other aspects of mucosal function and to assess the role of inflammation in the demonstrated defects. Specifically, we will determine if, in the same sheep model, 1) the sustained mucociliary dysfunction after antigen challenge is causally related to inflammation, 2) the depth and distribution of airway mucus influences the bronchial responsiveness to inhaled bronchoconstrictor aerosols, 3) the allergic airway is characterized by an inappropriate adaptation in epithelial water transport to osmotic stimuli and this abnormality is caused by inflammatory cell products, and 4) thermal stress produces differential vascular responses in allergic and non- allergic airways due to differences in mediator generation of autonomic responsiveness. The in vitro techniques will include the measurement of tracheal mucus velocity, respiratory mechanics, aerosol deposition, tracheal mucosal blood flow and tissue volume. In vitro techniques will include the measurement of mucus glycoprotein, ion, water fluxes and hydraulic conductivity in tracheal tissue, and determination of the interaction among ciliary beat frequency, mucus depth, mucus rheology and mucus transport rate. These physiologic parameters will be correlated with histopathologic and humoral indices (RIA and HPLC) of inflammation. Most of the proposed in vivo and in vitro methods have been previously used and validated in this and other laboratories. We expect to show that in the allergic airway, mucosal defects re involved in the abnormal airway responses to physical and pharmacologic stimuli and are related to inflammation. The results may form the basis for new treatment strategies in patients with bronchial asthma.

支气管哮喘的特征是气道通畅三联征 肌肉收缩、粘膜纤毛功能障碍和水肿。 两 这些表现涉及粘膜。 在前一次和 在目前的资助期间，我们在一个 尝试表征绵羊气道粘膜纤毛功能 过敏性支气管收缩模型。 这些研究 证明抗原攻击导致 粘膜纤毛清除，这与化学介质有关， 过敏反应，是由异常的气道分泌功能引起的， 并持续数天。 目前的总体目标 建议将这些意见扩展到其他方面， 粘膜功能，并评估炎症在 显示缺陷。 具体来说，我们将确定，在 相同的绵羊模型，1）持续的粘膜纤毛功能障碍后， 抗原攻击与炎症有因果关系，2）深度 气道粘液的分布影响支气管 对吸入性支气管收缩剂气雾剂的反应性，3） 过敏性气道的特征是不适当的适应， 上皮细胞对渗透压刺激的水转运和这种异常 是由炎症细胞产物引起的，以及4）热应激 在过敏性和非过敏性中产生不同的血管反应， 过敏性气道由于介质产生的差异， 自主反应 体外技术将包括 气管粘液流速测定，呼吸道 力学、气溶胶沉积、气管粘膜血流和 组织体积。 体外技术将包括测量 粘液糖蛋白，离子，水通量和水力 气管组织中的电导率，以及 纤毛搏动频率、粘液深度、粘液 流变学和粘液运输速率。 这些生理参数 与组织病理学和体液免疫指标（RIA）相关 和HPLC）。 大多数提议的体内和体内 体外方法先前已在本研究中使用并得到验证， 其他实验室。 我们希望在过敏性气道中， 粘膜缺损与气道对哮喘的异常反应有关， 物理和药理刺激，并与 炎症 这些结果可能会成为新疗法的基础 支气管哮喘患者的治疗策略