Pulmonary Exchange of Nitric Oxide: A Quantitative Description

一氧化氮（NO）是哺乳动物系统中普遍存在的具有生理活性的分子，最近在人类呼出的气体中被检测到。在肺部疾病存在时，呼出气体中的NO浓度会发生变化。呼气轮廓的形状反映了肺中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和患有炎症性肺部疾病的NO交换动力学和生理学的理解。此外，吸入性NO有望作为哮喘、肺动脉高压和成人呼吸窘迫综合征（ARDS）等疾病的治疗方法。气体吸入策略可以克服与静脉或气雾剂给药有关的许多问题。目前，关于NO在肺中的基本气体交换动力学的信息有限，主要是通过实验，很少关注建模作为理解实验结果的工具。许多炎症性疾病影响较小的气道（细支气管）和肺泡，这些气道基本上无法进行直接的实验测量。因此，理论建模为理解气道树内气体交换过程提供了一条重要途径。该项目的目标是：1)建立肺部内源性NO交换的数学模型；2)在一系列呼吸条件下使用一系列呼出曲线验证模型的性能；3)了解炎症对呼出曲线的影响；4)开发使用性NO作为治疗方法的治疗策略。该建议在理论和实验之间取得了很好的平衡，结果将提供有关肺中NO交换动力学的基本信息，从而提高我们对正常和病变肺的理解。＊＊＊

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. ***