HYPERPNEA AND PARENCHYMAL PATHOPHYSIOLOGY IN ASTHMA

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通气时发生支气管痉挛， 通过灭活表面活性剂降低实质顺应性， 动物我们对这种对肺实质的影响很感兴趣， 当我们观察到外周阻力（Rp）上升时， 在楔形中模拟局部HP后，外周顺应性福尔斯下降 高流量冷干燥空气的气道段。这导致了一个假设 HP通过以下方式影响人类肺实质功能 其机制：1）由于直接的炎症介质释放而增加Rp; 2）对表面活性剂功能的直接影响。 目前的项目旨在探索生理和 HP在正常人和哮喘患者中的生化作用。 具体而言，我们将通过以下方式寻找肺实质力学的变化： 测量肺的弹性回缩、顺应性和滞后， 这些变化对气道功能的影响。我们还将这些全肺 参数的变化，并立即灌洗刺激气道 并分段评估介质和表面活性剂的变化， 发展到HP。β-受体激动剂和外源性表面活性剂将 直接扰动系统，以建立 机制最后，我们将确定PEEP的影响和改变 肺容量对实质力学的影响，以及 软组织和气道。

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.