Stochastic Modeling Predictions for the Clearance of Insoluble Particles from the Tracheobronchial Tree of the Human Lung

Original Article

Abstract

Bronchial clearance of deposited particles was simulated using a stochastic model of the tracheobronchial tree. The clearance model introduced in this study considers (1) a continuous decrease of the mucus thickness from the trachea to the terminal bronchioles according to a linear or an exponential function, (2) the possibility of mucus discontinuities, which are mainly found in intermediate and distal airways of the tracheobronchial compartment, (3) mucus production in proximal airways, (4) a slow bronchial clearance phase due to the capture of a defined particle fraction fs in the periciliary sol phase, and (5) an eventual delay of the mucociliary transport at carinal ridges of airway bifurcations. Based on the concept of mucus volume conservation in single bifurcations, a reduction of the thickness of the mucus blanket from proximal to distal airways causes a significant increase of the mucus velocities in small ciliated airways compared to other stochastic modeling predictions assuming a constant thickness of the mucus layer throughout the conducting airways. This effect is further enhanced by the consideration of mucus discontinuities. In contrast, the ability of bronchial airways to produce a certain volume of mucus has a decreasing effect on the mucus velocities. In all generated clearance velocity models, mucociliary clearance is completely terminated within 24 h after exposure, consistent with the experimental evidence. Implementation of a slow bronchial clearance phase predicts a long-term retention fraction, which is fully cleared from the lung after several weeks. For 1-μm MMAD particles, 24-h retention varies between 0.42 and 0.52, in line with the suggestions of the ICRP. Mucus delay at carinal ridges only affects short-term clearance by increasing the retained particle fraction at a given time, while long-term retention is not influenced.

Keywords

Stochastic model Bronchial airways Mucus layer Particle deposition Slow bronchial clearance 

References

  1. Albert, R.E., Arnett, L.C., 1955. Clearance of radioactive dust from the human lung. AMA Arch. Ind. Health 12, 99–106.Google Scholar
  2. Albert, R.E., Lippmann, M., Briscoe, W., 1969. The characteristics of bronchial clearance in humans and the effects of cigarette smoking. Arch. Env. Health 18, 738–755.Google Scholar
  3. Anjilvel, S., Asgharian, B., 1995. A multiple-path model of particle deposition in the rat lung. Fund. Appl. Toxicol. 28, 41–50.CrossRefGoogle Scholar
  4. Asgharian, B., Hofmann, W., Miller, F.J., 2001. Mucociliary clearance of insoluble particles from the tracheobronchial airways of the human lung. J. Aerosol Sci. 32, 817–832.CrossRefGoogle Scholar
  5. Brain, J.D., Gehr, P., Karvet, R.I., 1984. Airway macrophages: The importance of the fixation method. Ann. Rev. Resp. Dis. 129, 823–826.Google Scholar
  6. Cuddihy, R.G., Yeh, H.C., 1988. Respiratory tract clearance of particles and substances dissociated from particles. In: Mohr, U. (Ed.), Inhalation Toxicology: The Design and Interpretation of Inhalation Studies and Their Use in Risk Assessment. Springer, Berlin, pp. 169–193.Google Scholar
  7. Gehr, P., Im Hof, V., Geiser, M., Schürch, S., 1991. The fate of particles deposited in the intrapulmonary conducting airways. J. Aerosol Med. 4, 349–361.CrossRefGoogle Scholar
  8. Geiser, M., Cruz-Orive, L., Im Hof, V., Gehr, P., 1990. Assessment of particle retention and clearance in the intrapulmonary conducting airways of hamster lungs with the fractionator. J. Microsc. 160, 75–88.Google Scholar
  9. Hofmann, W., Martonen, T., Menaché, M., 1990. A dosimetric model for localised radon progeny accumulations at tracheobronchial bifurcations. Rad. Prot. Dosim. 30, 245–259.Google Scholar
  10. Hofmann, W., Koblinger, L., 1992. Monte Carlo modeling of aerosol deposition in human lungs. Part III: Comparison with experimental data. J. Aerosol Sci. 23, 51–63.CrossRefGoogle Scholar
  11. Hofmann, W., Asgharian, B., Winkler-Heil, R., 2001a. Modeling intersubject variability of particle deposition in human lungs. J. Aerosol Sci. 33, 219–35.CrossRefGoogle Scholar
  12. Hofmann, W., Sturm, R., Asgharian, B., 2001b. Stochastic simulation of particle clearance in human bronchial airways. J. Aerosol Sci. 32(Suppl.), S807–S808.Google Scholar
  13. Hofmann, W., Asgharian, B., 2003. The effect of lung structure on mucociliary clearance and particle retention in human and rat lungs. Toxicol. Sci. 73, 448–456.CrossRefGoogle Scholar
  14. Hofmann, W., Sturm, R., 2004. Stochastic model of particle clearance in human bronchial airways. J. Aerosol Med. 17, 73–89.CrossRefGoogle Scholar
  15. International Commission on Radiological Protection (ICRP), 1994. Human respiratory tract model for radiological protection. Publication 66. Ann. ICRP, Pergamon Press, Oxford, UK.Google Scholar
  16. Iravani, J.D., Van As, A., 1972. Mucus transport in the tracheobronchial tree of normal and bronchitic rats. J. Pathol. 106, 81–93.CrossRefGoogle Scholar
  17. Koblinger, L., Hofmann, W., 1985. Analysis of human lung morphometric data for stochastic aerosol deposition calculations. Phys. Med. Biol. 30, 541–556.CrossRefGoogle Scholar
  18. Koblinger, L., Hofmann, W., 1990. Monte Carlo modeling of aerosol deposition in human lungs. Part I: Simulation of particle transport in a stochastic lung structure. J. Aerosol Sci. 21, 661–674.CrossRefGoogle Scholar
  19. Lee, P.S., Gerrity, T.R., Hass, F.J., Lourenco, R.V., 1979. A model for tracheobronchial clearance of inhaled particles in man and a comparison with data. IEEE Trans. Biomed. Eng. 26, 624–630CrossRefGoogle Scholar
  20. Luchtel, D.L., 1976. Ultrastructural observations on the mucous layer in pulmonary airways. J. Cell Biol. 70, 350a.Google Scholar
  21. Mercer, R.R., Russell M.L., Crapo, J.D., 1992. Mucous lining layers in human and rat airways. Ann. Rev. Resp. Dis. 145, 355.Google Scholar
  22. Mercer, R.R., Russell, M.L., Roggli, V.L., Crapo, J.D., 1994. Cell number and distribution in human and rat airways. Am. J. Resp. Cell Mol. Biol. 10, 613–624.Google Scholar
  23. Mussatto, D.J., Garrard, C.S., Lourenco, R.V., 1988. The effect of inhaled histamine on human tracheal mucus velocity and bronchial mucociliary clearance. Am. Rev. Resp. Dis. 138, 774–779.Google Scholar
  24. National Council on Radiation Protection and Measurements (NCRP), 1997. Deposition, retention, and dosimetry of inhaled radioactive substances, Report No. 125, Oxford.Google Scholar
  25. Oberdörster, G., 1988. Lung clearance of inhaled insoluble and soluble particles. J. Aerosol Med. 1, 289–330.CrossRefGoogle Scholar
  26. Raabe, O.G., Yeh, H.C., Schum, G.M., Phalen, R.F., 1976. Tracheobronchial geometry: Human, dog, rat, hamster — A compilation of selected data from the project respiratory tract deposition models. Report LF-53. Lovelace Foundation, Albuquerque, New Mexico.Google Scholar
  27. Scheuch, G., Stahlhofen, W., Heyder, J., 1996. An approach to deposition and clearance measurements in human airways. J. Aerosol Med. 9, 35–41.CrossRefGoogle Scholar
  28. Stahlhofen, W., Gebhart, J., Rudolf, G., Scheuch, G., 1986. Measurement of lung clearance with pulses of radioactivity-labelled aerosols. J. Aerosol Sci. 17, 330–336.Google Scholar
  29. Stahlhofen, W., Koebrich, R., Rudolf, G., Scheuch, G., 1990. Short-term and long-term clearance of particles from the upper human respiratory tract as a function of particle size. J. Aerosol Sci. 21(Suppl.), S407–S410.CrossRefGoogle Scholar
  30. Sturgess, J.M., 1977. The mucous lining of major bronchi in the rabbit lung. Am. Rev. Resp. Dis. 115, 819–827.Google Scholar
  31. Sturm, R., Hofmann, W., 2003. Mechanistic interpretation of the slow bronchial clearance phase. Rad. Prot. Dosim. 105, 101–104.Google Scholar
  32. Sturm, R., Hofmann, W., Scheuch, G., Sommerer, K., Svartengren, M., Camner, P., 2002. Particle clearance in human bronchial airways: Comparison of stochastic model predictions with experimental data. Ann. Occ. Hyg. 46(Suppl.), 329–333.CrossRefGoogle Scholar
  33. Weibel, E.R., 1963. Morphometry of the Human Lung. Academic Press, New York.Google Scholar
  34. Wolff, R.K., 1989. Mucociliary function. In: Parent, R.A. (Ed.), Comparative Biology of the Normal Lung. CRC Press, New York, pp. 659–680.Google Scholar
  35. Yeates, D.B., Gerrity, T.R., Garrard, C.S., 1982. Characteristics of tracheobronchial deposition and clearance in man. Ann. Occ. Hyg. 26, 245–257.CrossRefGoogle Scholar
  36. Yeh, H., Schum, G.M., 1980. Models of Human lung airways and their application to inhaled particle deposition. Bull. Math. Biol. 42, 461–80.MATHGoogle Scholar
  37. Yu, C.P., Hu, J.P., Yen, B.M., Spektor, D.M., Lippmann, M., 1986. Models for mucociliary particle clearance in lung airways. In: Lee, S.D., Schneider, T., Grant, L.D., Verkerk, P.J. (Eds.), Aerosols: Research, Risk Assessment and Control Strategies, MI, Lewis, Chelsea, pp. 569–578.Google Scholar

Copyright information

© Society for Mathematical Biology 2006

Authors and Affiliations

  1. 1.SalzburgAustria
  2. 2.Division of Physics and Biophysics, Department of Molecular BiologyUniversity of SalzburgSalzburgAustria

Personalised recommendations