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. ***
