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Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

Departments of ¹Biomedical Engineering, ²Chemical Engineering and Materials Science, and ³Pediatrics, and ⁴The General Clinical Research Center, University of California, Irvine, California 92697

Submitted 3 December 2003 ; accepted in final form 22 April 2004

Exhaled nitric oxide (NO) is a potential noninvasive index of lung inflammation and is thought to arise from the alveolar and airway regions of the lungs. A two-compartment model has been used to describe NO exchange; however, the model neglects axial diffusion of NO in the gas phase, and recent theoretical studies suggest that this may introduce significant error. We used heliox (80% helium, 20% oxygen) as the insufflating gas to probe the impact of axial diffusion (molecular diffusivity of NO is increased 2.3-fold relative to air) in healthy adults (21–38 yr old, n = 9). Heliox decreased the plateau concentration of exhaled NO by 45% (exhalation flow rate of 50 ml/s). In addition, the total mass of NO exhaled in phase I and II after a 20-s breath hold was reduced by 36%. A single-path trumpet model that considers axial diffusion predicts a 50% increase in the maximum airway flux of NO and a near-zero alveolar concentration (CA_NO) and source. Furthermore, when NO elimination is plotted vs. constant exhalation flow rate (range 50–500 ml/s), the slope has been previously interpreted as a nonzero CA_NO (range 1–5 ppb); however, the trumpet model predicts a positive slope of 0.4–2.1 ppb despite a zero CA_NO because of a diminishing impact of axial diffusion as flow rate increases. We conclude that axial diffusion leads to a significant backdiffusion of NO from the airways to the alveolar region that significantly impacts the partitioning of airway and alveolar contributions to exhaled NO.

gas exchange; model; exhaled breath

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