Pulmonary Exchange of Nitric Oxide: A Quantitative Description

9619340乔治·一氧化氮(NO)是哺乳动物体内普遍存在的一种具有生理活性的分子，最近在人类呼气中被检测到。呼气中的NO浓度在出现肺部疾病时会发生变化。呼气剖面的形状反映了肺内NO的潜在交换动力学，因此，可以作为一种工具来提高我们对正常人和炎症性肺部疾病患者的NO交换动力学和生理学的理解。此外，吸入性源性NO有望成为治疗哮喘、肺动脉高压和成人呼吸窘迫综合征(ARDS)等疾病的一种方法。气体吸入策略可以克服静脉或雾化给药带来的许多问题。目前，关于NO在肺内的基本气体交换动力学的有限信息一直以实验为主，很少注意将建模作为理解实验结果的工具。许多炎症性疾病影响到小气道(细支气管壁)和肺泡，而这些区域基本上无法直接进行实验测量。因此，理论建模提供了了解呼吸道内气体交换过程的重要途径，该项目的目标是1)建立内源性NO在肺内交换的数学模型，2)使用一系列呼吸条件下的呼气曲线来验证模型的性能，3)了解炎症对呼气曲线的影响，以及4)开发使用性源NO作为治疗的治疗策略。该提议在理论和实验之间取得了很好的平衡，结果将提供与肺内NO交换动力学相关的基本信息，这将提高我们对正常肺和病变肺的理解。***

9619340 George Nitric Oxide (NO) is a pervasive and physiologically active molecule in mammalian systems, and has recently been detected in the exhaled breath of humans. The concentration of NO in the exhaled breath changes in the presence of lung disease. The shape of the exhalation profile reflects the underlying exchange dynamics of NO in the lung, and, therefore, can be used as a tool to improve our understanding of NO exchange dynamics and physiology in both normals and those suffering from inflammatory lung diseases. In addition, inhaled erogenous NO holds promise as a therapy for diseases such as asthma, pulmonary hypertension, and Adult Respiratory Distress Syndrome (ARDS). A gas inhalation strategy can overcome many of the problems associated with intravenous or aerosol administration of drugs. Currently, the limited information available regarding the basic gas exchange dynamics of NO in the lungs has been dominated by experimentation with little attention paid to modeling as a tool to understand the experimental results. Many inflammatory diseases afflict the smaller airways (bronchioles) and alveoli which are essentially inaccessible to direct experimental measurement. Thus, theoretical modeling provides an important avenue to understanding the exchange process of gases within the airway tree, The goals of the project are to 1) develop a mathematical of endogenous NO exchange in the lungs, 2) validate the performance of the model using a series of exhalation profiles under a range, of breathing conditions, 3) understand the effect of inflammation on the exhalation profile, and 4) develop therapeutic strategies for using erogenous NO as a therapy. The proposal is well-balanced between theory and experiment, and the results will provide fundamental information related NO exchange dynamics in the, lungs that will improve our understanding of both normal and diseased lungs. ***