Method to Characterize Exhaled Nitric Oxide from the Airways Using a Sequence of Breathhold Maneuvers

Background: Exhaled nitric oxide (NO) arises from both airway and alveolar regions of the lungs, which provides an opportunity to characterize region-specific inflammation. Current methodologies rely on vital capacity breathing maneuvers and controlled exhalation flow rates, which can be difficult to perform, especially for young children and individuals with compromised lung function. In addition, recent theoretical and experimental studies demonstrate that gas-phase axial diffusion of NO has a significant impact on the exhaled NO signal. Technology: Researchers at the University of California have developed a new technique to characterize airway NO, which requires a series of progressively increasing breath-hold times followed by exhalation of only the airway compartment. Using our new technique, we determined values (means + SE) in healthy adults (20-38 yr, n = 8) for the airway diffusing capacity [4.5 + 1.6 pl/s-1 parts per billion (ppb)-1], the airway wall concentration (1,340 + 213 ppb), and the maximum airway wall flux (4,350 + 811 pl/s).

Relative to previously described single-breath techniques of the current art, our new breath-hold technique has two distinct advantages. First, the exhalation flow need not be controlled, providing a simpler maneuver to complete for both the subject and the investigator or clinician. Second, the technique provides improved accuracy (smaller confidence interval) for estimating DawNO relative to the single-breath technique with a 20-s breath hold and decreasing exhalation flow.

Thus, the technique is relatively simple to perform and does not require monitoring or control of exhalation flow, and determined airway NO parameters agree well with a previously described single-breath technique. In addition, the impact of two important physical and anatomical features, neglected for simplicity in previous models, have been included; namely, axial diffusion of NO in the gas phase and an increasing cross-sectional area of the airway tree with axial position (i.e., trumpet shape).

The new breath-hold technique may have potential to characterize airway NO exchange in subjects unable to perform single-breath exhalations.

Type of Offer: Licensing

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