Skip to main content
SpringerLink
Log in

Impact of Volume-Dependent Alveolar Diffusing Capacity on Exhaled Nitric Oxide Concentration

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Exhaled endogenous nitric oxide (NO) holds promise as a potential biomarker of pulmonary inflammation. Previous experimental and theoretical work has concluded that the alveolar concentration approaches a constant steady state value at end exhalation due to both a constant maximum flux or release of NO (Jmax,alv) and a constant diffusing capacity (DNO,alv) in the alveolar region. We have recently demonstrated that DNO,alv is not constant, but increases with alveolar volume (VA) given by the following average relationship: DNO,alv=48*V 2/3A ml/min/mmHg (where VA is expressed in liters, STPD). We investigated the potential impact of a variable DNO,alv on exhaled concentration by incorporating the volume dependence into the currently accepted two-compartment model for NO exchange dynamics. Our results suggest that the mechanism underlying the plateau in exhaled concentration is a constant ratio Jmax,alv/DNO,alv.This constant ratio requires a volume dependence of Jmax,alv similar to DNO,alv, and is likely due to a decreasing alveolar surface area during exhalation. © 2001 Biomedical Engineering Society.

PAC01: 8719Uv, 8710+e, 8715Vv, 8239Rt

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alving, K., E. Weitzberg, and J. M. Lundberg. Increased amount of nitric oxide in exhaled air of asthmatics. Eur. Respir. J.6:1368–1370, 1993.

    Google Scholar 

  2. Bannenberg, G. L., and L. E. Gustafsson. Stretch-induced stimulation of lower airway nitric oxide formation in the guinea-pig: Inhibition by gadolinium chloride. Pharm. Toxicol.81:13–18, 1997.

    Google Scholar 

  3. Davidson, M. R., and J. M. Fitzgerald. Transport of O2 along a model pathway through the respiratory region of the lung. Bull. Math. Biol.36:275–303, 1974.

    Google Scholar 

  4. DuBois, A. B., P. M. Kelley, J. S. Douglas, and V. Mohsenin. Nitric oxide production and absorption in trachea, bronchi, bronchioles, and respiratory bronchioles of humans. J. Appl. Physiol.86:159–167, 1999.

    Google Scholar 

  5. Fukuto, J. M. Chemistry of nitric oxide: Biologically relevant aspects. In: Nitric Oxide: Biochemistry, Molecular Biology, and Therapeutic Implications, edited by Ignarro and Murad. San Diego: Academic, 1995, pp. 1–15.

    Google Scholar 

  6. Gaston, B., J. M. Drazen, J. Loscalzo, and J. S. Stamler. The biology of nitrogen oxides in the airways. Am. J. Respir. Crit. Care Med. 149:538–551, 1994.

    Google Scholar 

  7. Hung, J. F., K. Fang, R. Malik, A. Snyder, N. Malhotra, T. A. Platts-Mills, and B. Gaston. Endogenous airway acidification. Implications for asthma pathophysiology. Am. J. Respir. Crit. Care Med.161:694–699, 2000.

    Google Scholar 

  8. Hyde, R. W., E. J. Geigel, A. J. Olszowka, J. A. Krasney, R. E. Forster, M. J. Utell, and M. W. Frampton. Determination of production of nitric oxide by lower airways: Theory. J. Appl. Physiol.82:1290–1296, 1997.

    Google Scholar 

  9. Kharitonov, S., K. Alving, and P. J. Barnes. Exhaled and nasal nitric oxide measurements: Recommendations. The European Respiratory Society Task Force. Eur. Respir. J.10:1683–1693, 1997.

    Google Scholar 

  10. Moilanen, E., and H. Vapaatalo. Nitric oxide in inflammation and immune response. Ann. Med.27:359–367, 1995.

    Google Scholar 

  11. Paiva, M., and L. A. Engel. The anatomical basis for the sloping N2 plateau. Respir. Physiol.44:325–337, 1981.

    Google Scholar 

  12. Pietropaoli, A. P., I. B. Perillo, A. Torres, P. T. Perkins, L. M. Frasier, M. J. Utell, M. W. Frampton, and R. W. Hyde. Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans. J. Appl. Physiol.87:1532–1542, 1999.

    Google Scholar 

  13. Scheid, P., M. P. Hlastala, and J. Piiper. Inert gas elimination from lungs with stratified inhomogeneity: Theory. Respir. Physiol.44:299–309, 1981.

    Google Scholar 

  14. Silkoff, P. E., P. A. McClean, A. S. Slutsky, H. G. Furlott, E. Hoffstein, S. Wakita, K. R. Chapman, J. P. Szalai, and N. Zamel. Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. Am. J. Respir. Crit. Care Med.155:260–267, 1997.

    Google Scholar 

  15. Silkoff, P. E., J. T. Sylvester, N. Zamel, and S. Permutt. Airway nitric oxide diffusion in asthma. Role in pulmonary function and bronchial responsiveness. Am. J. Respir. Crit. Care Med.161:1218–1228, 2000.

    Google Scholar 

  16. Six, D. P., W. R. de Vries, and S. C. Luijendijk. Sloping alveolar plateaus of He and SF6 measured in excised cat lungs ventilated at constant volume by pressure changes. Respir. Physiol.83:277–293, 1991.

    Google Scholar 

  17. Slutsky, A. S., and J. M. Drazen. Recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide in adults and children 1999. Am. J. Respir. Crit. Care Med.160:2104–2117, 1999.

    Google Scholar 

  18. Staub, N. C., Respiration. Annu. Rev. Physiol.31:173–202, 1969.

    Google Scholar 

  19. Stewart, T. E., F. Valenza, S. P. Reveiro, A. D. Wener, G. Volgyesi, J. Brendan, M. Mullen, and A. S. Slutksy. Increased nitric oxide in exhaled gas as an early marker of lung inflammation in a model of sepsis. Am. J. Respir. Crit. Care Med.151:713–718, 1995.

    Google Scholar 

  20. Tsoukias, N. M., D. Dabdub, A. F. Wilson, and S. C. George. Effect of alveolar volume and sequential filling on the diffusing capacity of the lungs. I. Theory. Respir. Physiol.120:231–250, 2000.

    Google Scholar 

  21. Tsoukias, N. M., and S. C. George. A two-compartment model of pulmonary nitric oxide exchange dynamics. J. Appl. Physiol.85:653–666, 1998.

    Google Scholar 

  22. Tsoukias, N. M., Z. Tannous, A. F. Wilson, and S. C. George. Single-exhalation profiles of NO and CO2 in humans: Effect of dynamically changing flow rate. J. Appl. Physiol.85:642–652, 1998.

    Google Scholar 

  23. Tsoukias, N. M., A. F. Wilson, and S. C. George. Effect of alveolar volume and sequential filling on the diffusing capacity of the lungs. II. Experiment. Respir. Physiol.120:251–271, 2000.

    Google Scholar 

  24. Weibel, E. R., P. Untersee, J. Gil, and M. Zulauf. Morphometric estimation of pulmonary diffusion capacity. VI. Effect of varying positive pressure inflation of air spaces. Respir. Physiol.18:285–308, 1973.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering and Materials Science, University of California, Irvine, Irvine, CA

    Nikolaos M. Tsoukias & Steven C. George

  2. Center for Biomedical Engineering, University of California, Irvine, Irvine, CA

    Steven C. George

Authors
  1. Nikolaos M. Tsoukias
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven C. George
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsoukias, N.M., George, S.C. Impact of Volume-Dependent Alveolar Diffusing Capacity on Exhaled Nitric Oxide Concentration. Annals of Biomedical Engineering 29, 731–739 (2001). https://doi.org/10.1114/1.1397786

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1114/1.1397786

Search

Navigation