HYPERPNEA AND PARENCHYMAL PATHOPHYSIOLOGY IN ASTHMA

哮喘的呼吸过度和实质病理生理学

• 批准号: 2771169
• 负责人: David A Kaminsky
• 金额: $ 9.05万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/2771169
• 关键词: asthma; biochemistry; bronchoscopy; human subject; hyperpnea; isoproterenol; lung alveolus; lung lavage; methacholine; pulmonary respiration; pulmonary surfactants; respiratory airflow disorder; respiratory airflow measurement; respiratory airway pressure; respiratory airway volume; respiratory function; stimulant /agonist; stop flow technique; surfactant

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.

绩高（HP）对肺功能具有重要影响。它刺激 运动或过度换气过程中哮喘的支气管痉挛，可能 通过灭活表面活性剂在 动物。我们对这种对实质肺的影响很感兴趣 当我们观察到外围电阻（RP）上升时，力学 在楔形的模拟本地HP之后，外围合规性下降 气道细分市场，带有高流冷的干燥空气。这导致了假设 HP会影响实质肺。通过以下 机制：1）直接炎症介质释放引起的RP增加； 2）直接影响表面活性剂功能。 当前项目旨在探索生理和 HP对人类的生化作用，无论是正常还是哮喘。 具体而言，我们将通过 测量肺弹性后坐力，合规性和滞后，并相关 这些变化对气道功能。我们还将联系这些全肺 RP变化的参数，并立即向刺激的气道灌输 和细分以评估介体和表面活性剂的变化 遵循HP。然后，β-激动剂和外源表面活性剂将 可以直接扰动系统以建立 机制。最后，我们将确定窥视和改变的影响 在实质力学上的肺体积和相互依赖性 实质和气道。