OZONE EFFECT ON PERIPHERAL AIRWAY FUNCTION

臭氧对周围气道功能的影响

基本信息

批准号：
2226817
负责人：
Arthur N Freed
金额：
$ 32.3万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-08-01 至 1998-07-31
项目状态：
已结题

项目摘要

Exposure to ozone (O3) causes focal lesions throughout the lung: alters airway function, and increases airway reactivity. These local effects are modulated by the magnitude of ozonolysis, the capacity of the antioxidant system, and the extent of mediator metabolism. The outcome of O3 exposure can be assessed by monitoring changes in airway structure and function. However, because the primary site of O3-induced injury is located in the lung periphery: and peripheral airways account for only a fraction of the total airway resistance, it is unlikely that conventional measurements of pulmonary function could reliably detect the initial changes in peripheral airways caused by O3. Thus, a bronchoscope will be used to study canine peripheral airway responses to O3. The relationship between acute O3- induced changes in peripheral airway morphology and transient changes in peripheral airway function and reactivity will be examined. These initial O3-induced events will be followed through time to document the progressive changes in peripheral airway and vascular structure and physiology that occur during subacute exposures to low concentrations of O3. Three hypotheses will be tested: 1) O3-induced injury is heterogeneously distributed and associated with local changes in peripheral airway function and reactivity, 2) A functional transition from a muscarinic-dependent to a muscarinic-independent mechanism occurs during prolonged periods of exposure to low concentrations of O3 and contributes to the development of airway hyperreactivity, and 3) Local antioxidant and media for concentrations determine the magnitude of O3-induced injury and modulate local changes in peripheral airway function and reactivity. In testing these hypotheses, the location and magnitude of O3-induced injury, bronchovascular hyperpermeability, and inflammation will be examined in relation to local changes in peripheral airway function and reactivity. Local concentrations of lipid peroxidation products, antioxidants, and biochemical mediators associated with O3-induced changes in peripheral airway function and reactivity will be determined using low volume bronchial lavage. Finally, anti-inflammatory drugs and antioxidant supplementation will be used in an attempt to reduce or eliminate oxidant- induced injury. The effects of these interventions on peripheral airway morphology, function, and reactivity will be documented, and should provide insights into the underlying mechanisms that mediate the extent of O3-induced damage and the subsequent changes that occur in peripheral airway function and reactivity.

暴露于臭氧（O3）会导致整个肺部局灶性病变：变化气道功能，并增加气道反应性。这些局部影响是由臭氧溶解的大小调节，抗氧化剂的能力系统，以及介体代谢的程度。 O3暴露的结果可以通过监视气道结构和功能的变化来评估。但是，由于O3诱导的损伤的主要部位位于肺外围：外围气道仅占一小部分总气道阻力，不太可能进行常规测量肺功能可以可靠地检测到周围的初始变化由O3引起的气道。因此，支气管镜将用于研究犬外围气道对O3的响应。急性O3-之间的关系诱发外围气道形态的变化和瞬态变化将检查外围气道功能和反应性。这些最初 O3引起的事件将在时间上遵循，以记录周围气道和血管结构的进行性变化以及亚急性暴露于低浓度的生理学 O3。将测试三个假设：1）O3诱导的伤害为异质分布，并与本地变化相关联外围气道功能和反应性，2）从毒蕈碱依赖于毒蕈碱独立的机制发生在长时间暴露于低浓度的O3并贡献开发气道高反应性，3）局部抗氧化剂和培养基的浓度决定了O3诱导的损伤的大小和调节外围气道功能和反应性的局部变化。在测试这些假设，O3诱导的损伤的位置和幅度，将检查支气管血管血管过敏性和炎症与周围气道功能和反应性的局部变化有关。脂质过氧化产物，抗氧化剂和局部浓度与O3诱导的周围变化相关的生化介体气道功能和反应性将使用低体积确定支气管灌洗。最后，抗炎药和抗氧化剂补充将用于减少或消除氧化剂 - 诱发受伤。这些干预措施对外围气道的影响形态学，功能和反应性将被记录在案，应提供有关介导的潜在机制的见解 O3诱导的损坏以及周围发生的随后变化气道功能和反应性。