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) 会导致整个肺部的局灶性病变：改变气道功能，并增加气道反应性。这些局部效应是受臭氧分解程度、抗氧化剂能力的调节系统和介质代谢的程度。 O3 暴露的结果可以通过监测气道结构和功能的变化来评估。然而，由于 O3 引起的损伤的主要部位位于肺外周：外周气道仅占肺外周的一小部分总气道阻力，常规测量不太可能肺功能可以可靠地检测外周血流量的初始变化由 O3 引起的气道。因此，支气管镜将用于研究犬类外周气道对 O3 的反应。急性O3-之间的关系引起周围气道形态的变化和短暂的变化将检查外周气道功能和反应性。这些最初的 O3 引发的事件将随着时间的推移进行跟踪，以记录周围气道和血管结构的进行性变化亚急性暴露于低浓度的物质时发生的生理学变化 O3。将测试三个假设：1）O3 引起的损伤是异质分布并与局部变化相关外周气道功能和反应性，2）从功能转变毒蕈碱依赖型到毒蕈碱独立型机制发生在长时间暴露于低浓度的 O3 并有助于气道高反应性的发展，以及 3) 局部抗氧化剂和介质浓度决定 O3 诱导损伤的程度调节周围气道功能和反应性的局部变化。在检验这些假设、O3 引起的损伤的位置和程度，支气管血管通透性过高和炎症将在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、抗氧化剂和的局部浓度与 O3 诱导的外周细胞变化相关的生化介质将使用低容量确定气道功能和反应性支气管灌洗。最后，抗炎药和抗氧化剂补充剂将用于尝试减少或消除氧化剂诱发损伤。这些干预措施对周围气道的影响形态、功能和反应性将被记录下来，并且应该提供对调节程度的基本机制的见解 O3 引起的损伤以及随后发生的外周变化气道功能和反应性。