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

Abstract

Shin, Hye-Won, Peter Condorelli, Christine M. Rose-Gottron, Dan M. Cooper, and Steven C. George. Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox. J Appl Physiol 97: 874 -882, 2004. First published April 30, 2004 10.1152/ japplphysiol.01297.2003.-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 ϭ 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 CANO (range 1-5 ppb); however, the trumpet model predicts a positive slope of 0.4 -2.1 ppb despite a zero CANO 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 NITRIC OXIDE (NO) performs many important functions in the lungs and has been regarded as a potential noninvasive marker of lung inflammation (2). The characteristics of NO gas exchange are unique compared with other endogenous gases because exhaled NO is thought to have a significant alveolar and airway source (6,8,15,22). A two-compartment model is commonly used to characterize NO exchange dynamics for healthy and diseased lungs (9,11,13,20,21,23,24,27,29), by partitioning exhaled NO into airway and alveolar contributions using three flow-independent NO exchange parameters: maximum flux of NO from the airways (JЈaw NO ), the diffusing capacity of NO in the airways (Daw NO ), and the steady-state alveolar concentration (CA NO ). However, the two-compartment model considers only convection of NO in the airways as a transport mechanism and has neglected axial diffusion of NO in the gas phase to preserve mathematical simplicity.Recently, our laboratory (17) and others (31) separately demonstrated theoretically that axial diffusion may play an important role in NO transport. During exhalation, the concentration of NO is higher in the airways compared with the alveoli, creating a gradient for diffusion of NO from the air...

Smokers Have Reduced Nitric Oxide Production by Conducting Airways but Normal Levels in the Alveoli

“…Shin et al also studied the rate of axial diffusion during ventilation with heliox (20% oxygen and 80% helium) and experimentally confirmed the importance of axial diffusion during single breath constant exhalations such as employed by all of the studies listed in Table 3 (Shin et al, 2004). These studies indicate that this back diffusion of NO from the conducting airways into the alveoli can reduce exhaled NO by as much as 50%.…”

Axial distribution heterogeneity of nitric oxide airway production in healthy adults

“…Experiments using heliox instead of air, hence amplifying the back diffusion, led to very consistent results in healthy adults (11,19).…”

“…Heliox criterion. At 50 ml/s of expiratory flow, FE NO was shown to systematically decrease when heliox (21% oxygen, 79% helium) was substituted for air in normal subject lungs (11,19). We defined FNO He ϭ FE NO,He /FE NO ,…”

How accurately should we estimate the anatomical source of exhaled nitric oxide?

“…The algorithms were equally simple involving linear fits of experimental measurements in which the slope and intercept reflected region-specific (i.e., alveolar) NO parameters (9,14,20,22). While these early models were elegant in their simplicity and ability to explain the strong flow dependence of exhaled NO, they neglected potentially important physical and physiological phenomena such as axial (or longitudinal) gas phase diffusion, the trumpet shape of the airway cross-sectional area, and spatial heterogeneity in flow.Recently, more advanced models have been developed (18,23) and validated with new experimental measurements (16,17) demonstrating the importance of axial diffusion of NO. In particular, the airway source of NO is large enough to create an axial gradient in NO concentration that leads to diffusion of NO from the airway tree into the alveolar region (i.e., "backdiffusion").…”

“…Recently, more advanced models have been developed (18,23) and validated with new experimental measurements (16,17) demonstrating the importance of axial diffusion of NO. In particular, the airway source of NO is large enough to create an axial gradient in NO concentration that leads to diffusion of NO from the airway tree into the alveolar region (i.e., "backdiffusion").…”