Technique to Characterize NIitric Oxide Exchange in the Lungs
Background: It has been reported that the concentration of Nitric oxide (NO) in the exhaled breath was substantially elevated in patients with asthma who were not treated with corticosteroids, suggesting that exhaled NO was a potential noninvasive index of assessing lung and airway inflammation. Because NO exchange dynamics are significantly different from other well-studied gases such as carbon dioxide, new models and analytical methods are needed to understand the underlying physiology and gas exchange mechanisms. Technology: University of California researchers have developed a simple two-compartment model to represent many of the observed experimental observations of exhaled NO concentration, including the marked dependence on exhalation flow rate. A patient inhales NO-free air to total lung capacity and immediately begins to exhale against a flow restrictor. The concentration of NO in the exhaled breath is measured as a function of exhaled volume. By applying a model to the data which considers the trumpet shape of the airway tree and axial diffusion of NO, peripheral and proximal NO exchange in the lungs can be determined. The model characterizes NO exchange by using three flow-independent exchange parameters. Two of the parameters describe the airway compartment (airway NO diffusing capacity and either the maximum airway wall NO flux or the airway wall NO concentration), and the third parameter describes the alveolar region (steadystate alveolar NO concentration). A potential advantage of the two-compartment model is the ability to partition exhaled NO into an airway and alveolar source and thus improve the specificity of detecting altered NO exchange dynamics that differentially impact these regions of the lungs. Several analytical techniques have been developed to estimate the flow-independent parameters in both health and disease. The techniques utilize either multiple vital capacity maneuvers at two or more constant exhalation flow rates or a single vital capacity maneuver in which the flow rate is dynamically altered during the exhalation. Future studies will focus on improving our fundamental understanding of NO exchange dynamics, the analytical techniques used to characterize NO exchange dynamics, as well as the physiological interpretation and the clinical relevance of the flow-independent parameters. Application: Early reports suggest the flow-independent NO parameters are uniquely altered in several disease states such as asthma, cystic fibrosis, scleroderma, alveolitis, COPD, and allergic rhinitis and thus may provide pathophysiological insight or assist in the clinical management of inflammatory lung diseases.
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