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

J Appl Physiol (1985). 2004 Sep;97(3):874-82. doi: 10.1152/japplphysiol.01297.2003. Epub 2004 Apr 30.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Adult
  • Computer Simulation
  • Diffusion
  • Female
  • Helium / administration & dosage*
  • Helium / metabolism*
  • Humans
  • Lung / physiology*
  • Male
  • Models, Biological
  • Nitric Oxide / metabolism*
  • Oxygen / administration & dosage*
  • Oxygen / metabolism*
  • Pulmonary Alveoli / physiology
  • Pulmonary Gas Exchange / physiology*
  • Respiration*
  • Respiratory Function Tests / methods*


  • Helium
  • Nitric Oxide
  • heliox
  • Oxygen