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HYPERPNEA AND PARENCHYMAL PATHOPHYSIOLOGY IN ASTHMA

哮喘的呼吸过度和实质病理生理学

基本信息

批准号：
6056082
负责人：
David A Kaminsky
金额：
$ 12.37万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
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：
1995-09-30 至 2000-08-31
项目状态：
已结题

项目摘要

Hyperpnea (HP) has important effects on lung function. It stimulates bronchospasm in asthmatics during exercise or hyperventilation, and may reduce parenchymal compliance through inactivation of surfactant in animals. We became intrigued with this effect on parenchymal lung mechanics when we observed that peripheral resistance (Rp) rises and peripheral compliance falls following simulated local HP in a wedged airway segment with high-flow cold,dry air. This led to the hypothesis that HP affects parenchymal lung.function in humans by the following mechanisms: 1) increased Rp due to direct inflammatory mediator release; and 2) direct effects on surfactant function. The current project is designed to explore the physiological and biochemical effects of HP in humans, both normal and asthmatic. Specifically, we will look for changes in parenchymal lung mechanics by measuring lung elastic recoil, compliance and hysteresis, and relate these changes to airway function. We will also relate these whole-lung parameters to changes in Rp, and immediately lavage the stimulated airway and segment to assess the changes in mediators and surfactant that may develop following HP. Beta-agonists and exogenous surfactant will then be given to directly perturbate the system in order to establish mechanism. Finally, we will determine the effects of PEEP and alterations in lung volume on parenchymal mechanics, and the interdependence of the parenchyma and airways.

呼吸过度（HP）对肺功能有重要影响。它刺激哮喘患者在运动或过度换气期间发生支气管痉挛，并且可能通过表面活性剂失活降低实质顺应性动物。我们对这种对肺实质的影响很感兴趣当我们观察到外围阻力 (Rp) 上升并且在楔形区域中模拟局部 HP 后，外围顺应性会下降气道段有高流量冷、干燥空气。这导致了假设 HP 通过以下方式影响人类肺实质功能机制：1）由于直接炎症介质释放而导致Rp增加； 2) 对表面活性剂功能的直接影响。当前的项目旨在探索生理和 HP 对正常人和哮喘患者的生化影响。具体来说，我们将通过以下方式寻找肺实质力学的变化：测量肺弹性反冲力、顺应性和滞后性，并将其关联起来这些气道功能的变化。我们还将把这些全肺联系起来参数以改变 Rp，并立即冲洗受刺激的气道和部分来评估介体和表面活性剂的变化，这些变化可能跟随HP发展。然后β-激动剂和外源性表面活性剂可以直接扰动系统以建立机制。最后，我们将确定 PEEP 和改变的效果肺容量对实质力学的影响，以及实质和气道。