Advertisement

Annals of Biomedical Engineering

, Volume 38, Issue 12, pp 3535–3549 | Cite as

The Role of Airway Epithelium in Replenishment of Evaporated Airway Surface Liquid From the Human Conducting Airways

  • N. J. Warren
  • E. J. Crampin
  • M. H. TawhaiEmail author
Article

Abstract

This article presents a multi-scale computational model describing the transport of water vapor and heat within the human conducting airways and its interaction with cellular fluid transport kinetics. This tight coupling between the cell and the evaporative flux allows the periciliary liquid (PCL) depth to be investigated within the context of a geometric framework of the human conducting airways with spatial and temporal variations. Within the in vivo airway, the epithelium is not the only source of fluid available for hydration of the PCL, and fluid may also be supplied from submucosal glands (SMGs) or via axial transport of the PCL. The model predicts that without fluid supplied by either SMGs or via PCL transport, significant dehydration would occur under normal breathing conditions. Previous studies have suggested that PCL transport from the periphery to the trachea would require absorption of the fluid by the epithelium; here we show that this can theoretically be sustained by the evaporative load under normal breathing conditions. SMGs could also provide a significant supply of fluid for airway hydration, a hypothesis which is corroborated by comparing the distribution of SMGs as a function of airway generation with the distribution of airway evaporative flux.

Keywords

Airway evaporation Periciliary liquid Multi-scale modeling Fluid secretion Submucosal gland Periciliary liquid transport 

References

  1. 1.
    Ballard, S. T., and D. Spadafora. Fluid secretion by submucosal glands of the tracheobronchial airways. Respir. Physiol. Neurobiol., 159(3):271–277, 2007.CrossRefPubMedGoogle Scholar
  2. 2.
    Ballard, S. T., L. Trout, Z. Bebok, E. J. Sorscher, and A. Crews. Cftr involvement in chloride, bicarbonate, and liquid secretion by airway submucosal glands. AJP - Lung Cell. Mol. Physiol. 277(4):L694–L699, 1999.Google Scholar
  3. 3.
    Blake, J. R. Mechanics of ciliary transport. Cell Motil. Suppl. 1:41–45, 1982.CrossRefGoogle Scholar
  4. 4.
    Blake, J. R. Mechanics of muco-ciliary transport. J. Appl. Math., 32(1–3):69–87, 1984.Google Scholar
  5. 5.
    Boucher, R. C. Airway surface dehydration in cystic fibrosis: pathogenesis and therapy. Annu. Rev. Med. 58(1):157–170, 2007.CrossRefPubMedGoogle Scholar
  6. 6.
    Boucher, R. C. Cystic fibrosis: a disease of vulnerability to airway surface dehydration. Trends Mol. Med. 13(6):231–240, 2007.CrossRefPubMedGoogle Scholar
  7. 7.
    Boucher, R. C., M. J. Stutts, P. A. Bromberg, and J. T. Gatzy. Regional differences in airway surface liquid composition. J. Appl. Physiol. 50(3):613–620, 1981.PubMedGoogle Scholar
  8. 8.
    Choi, J.-I., and C. S. Kim. Mathematical analysis of particle deposition in human lungs: an improved single path transport model. Inhal. Toxicol. 19(11):925–939, 2007.CrossRefPubMedGoogle Scholar
  9. 9.
    Cole, P. The Respiratory Role of the Upper Airways: A Selective Clinical and Pathophysiological Review. New York: Decker Inc., 1992.Google Scholar
  10. 10.
    Daviskas, E., I. Gonda, and S. D. Anderson. Mathematical modeling of heat and water transport in human respiratory tract. J. Appl. Physiol. 69(1):362–372, 1990.PubMedGoogle Scholar
  11. 11.
    Daviskas, E., I. Gonda, and S. D. Anderson. Local airway heat and water vapour losses. Respir. Physiol. 84(1):115–132, 1991.CrossRefPubMedGoogle Scholar
  12. 12.
    Ficker, J. H. Physiology and pathophysiology of bronchial secretion. Pneumologie 62(Suppl 1):11–13, 2008.CrossRefGoogle Scholar
  13. 13.
    Folkesson, H. G., M. A. Matthay, A. Frigeri, and A. S. Verkman. Transepithelial water permeability in microperfused distal airways. Evidence for channel-mediated water transport. J. Clin. Invest. 97(3):664–671, 1996.CrossRefPubMedGoogle Scholar
  14. 14.
    Freund, B., and A. Youn. Environmental influences on body fluid balance during exercise—cold exposure. Technical report. Natick, MA: Army Research Inst. of Environmental Medicine.Google Scholar
  15. 15.
    Fulford, G. R., and J. R. Blake. Muco-ciliary transport in the lung. J. Theor. Biol. 121(4):381–402, 1986.CrossRefPubMedGoogle Scholar
  16. 16.
    Hanna, L. M. Modelling of Heat and Water Vapour Transport in the Human Respiratory Tract. PhD thesis, University of Pennsylvania, Philadelphia.Google Scholar
  17. 17.
    Ingenito, E. P., J. Solway, E. R. McFadden, B. M. Pichurko, E. G. Cravalho, and J. M. Drazen. Finite difference analysis of respiratory heat transfer. J. Appl. Physiol. 61(6):2252–2259, 1986.PubMedGoogle Scholar
  18. 18.
    Jiang, C., W. Finkbeiner, J. Widdicombe, P. B. McCray, and S. S. Miller. Altered fluid transport across airway epithelium in cystic fibrosis. Science 262:424–427, 1993.CrossRefPubMedGoogle Scholar
  19. 19.
    Kilgour, E., N. Rankin, S. Ryan, and R. Pack. Mucociliary function deteriorates in the clinical range of inspired air temperature and humidity. Intensive Care Med. 30(7):1491–1494, 2004.CrossRefPubMedGoogle Scholar
  20. 20.
    King, M., M. Agarwal, and J. Shukla. A planar model for mucociliary transport: effect of mucus viscoelasticity. Biorheology 30:49–61, 1993.PubMedGoogle Scholar
  21. 21.
    Liu, J., and R. Ewing. An operator splitting method for nonlinear reactive transport equations and its implementation based on dll and com. In: Current Trends in High Performance Computing and Its Applications. Berlin: Springer, 2005, pp. 93–102.Google Scholar
  22. 22.
    Livraghi, A., B. R. Grubb, E. J. Hudson, K. J. Wilkinson, J. K. Sheehan, M. A. Mall, W. K. O’Neal, R. C. Boucher, and S. H. Randell. Airway and lung pathology due to mucosal surface dehydration in {beta}-epithelial na+ channel-overexpressing mice: role of tnf-{alpha} and il-4r{alpha} signaling, influence of neonatal development, and limited efficacy of glucocorticoid treatment. J. Immunol. 182(7):4357–4367, 2009.CrossRefPubMedGoogle Scholar
  23. 23.
    Matsui, H., S. H. Randell, S. W. Peretti, C. William-Davis, and R. C. Boucher. Coordinated clearance of periciliary liquid and mucus from airway surfaces. J. Clin. Invest. 102(6):1125–1131, 1998.CrossRefPubMedGoogle Scholar
  24. 24.
    McFadden, E. R., B. M. Pichurko, H. F. Bowman, E. Ingenito, S. Burns, N. Dowling, and J. Solway. Thermal mapping of the airways in humans. J. Appl. Physiol. 58(2):564–570, 1985.PubMedGoogle Scholar
  25. 25.
    Mercer, R. R., M. L. Russell, V. L. Roggli, and J. D. Crapo. Cell number and distribution in human and rat airways. Am. J. Respir. Cell Mol. Biol. 10(6):613–624, 1994.PubMedGoogle Scholar
  26. 26.
    Mercke, U. The influence of varying air humidity on mucociliary activity. Acta Otolaryngol. 79(1–2):133–139, 1975.CrossRefPubMedGoogle Scholar
  27. 27.
    Mercke, U., and N. G. Toremalm. Air humidity and mucociliary activity. Ann. Otol. Rhinol. Laryngol. 85(1 Pt 1):32–37, 1976.PubMedGoogle Scholar
  28. 28.
    Mitchell, J. W., E. R. Nadel, and J. A. Stolwijk. Respiratory weight losses during exercise. J. Appl. Physiol. 32(4):474–476, 1972.PubMedGoogle Scholar
  29. 29.
    Nadel, J. A., B. Davis, and R. J. Phipps. Control of mucus secretion and ion transport in airways. Annu. Rev. Physiol. 41(1):369–381, 1979.CrossRefPubMedGoogle Scholar
  30. 30.
    Perry, R., and D. Green. Perry’s Chemical Engineers’ Handbook, 7th ed. McGraw-Hill, 1997.Google Scholar
  31. 31.
    Phillips, J. E., L. B. Wong, and D. B. Yeates. Bidirectional actively coupled water transport across tracheal epithelium. Resp. Crit. Care Med. 157(3):A848, 1998.Google Scholar
  32. 32.
    Promvonge, P., and S. Eiamsa-ard. Heat transfer augmentation in a circular tube using v-nozzle turbulator inserts and snail entry. Exp. Therm. Fluid Sci. 32(1):332–340, 2007.CrossRefGoogle Scholar
  33. 33.
    Quinton, P. M. Composition and control of secretions from tracheal bronchial submucosal glands. Nature 279(5713):551–552, 1979.CrossRefPubMedGoogle Scholar
  34. 34.
    Ryan, S. N., N. Rankin, E. Meyer, and R. Williams. Energy balance in the intubated human airway is an indicator of optimal gas conditioning. Crit. Care Med. 30(2):355–361, 2002.CrossRefPubMedGoogle Scholar
  35. 35.
    Saidel, G. M., K. L. Kruse, and F. P. Primiano. Model simulation of heat and water transport dynamics in an airway. J. Biomech. Eng. 105(2):188–193, 1983.CrossRefPubMedGoogle Scholar
  36. 36.
    Salinas, D., P. M. Haggie, J. R. Thiagarajah, Y. Song, K. Rosbe, W. E. Finkbeiner, D. W. Nielson, and A. S. Verkman. Submucosal gland dysfunction as a primary defect in cystic fibrosis. FASEB J. 19(3):431–433, 2005.PubMedGoogle Scholar
  37. 37.
    Sauret, V., P. M. Halson, I. W. Brown, J. S. Fleming, and A. G. Bailey. Study of the three-dimensional geometry of the central conducting airways in man using computed tomographic (ct) images. J. Anat. 200(Pt 2):123–134, 2002.CrossRefPubMedGoogle Scholar
  38. 38.
    Sleigh, M. A. The physiology of cilia and mucociliary interactions. Annu. Rev. Physiol. 52(1):137–155, 1990.CrossRefPubMedGoogle Scholar
  39. 39.
    Sleigh, M. A., J. R. Blake, and N. Liron. The propulsion of mucus by cilia. Am. Rev. Respir. Dis. 137(3):726–741, 1988.PubMedGoogle Scholar
  40. 40.
    Tarran, R., B. Button, and R. C. Boucher. Regulation of normal and cystic fibrosis airway surface liquid volume by phasic shear stress. Annu. Rev. Physiol. 68(1):543–561, 2006.CrossRefPubMedGoogle Scholar
  41. 41.
    Tarran, R., B. Button, M. Picher, A. M. Paradiso, C. M. Ribeiro, E. R. Lazarowski, L. Zhang, P. L. Collins, R. J. Pickles, J. J. Fredberg, and R. C. Boucher. Normal and cystic fibrosis airway surface liquid Hhomeostasis: the effects of phasic shear stress and viral infections. J. Biol. Chem. 280(42):35751–35759, 2005.CrossRefPubMedGoogle Scholar
  42. 42.
    Tawhai, M. H., and P. J. Hunter. Modeling water vapor and heat transfer in the normal and the intubated airways. Ann. Biomed. Eng. 32(4):609–622, 2004.CrossRefPubMedGoogle Scholar
  43. 43.
    Tos, M. Development of the tracheal glands in man. Dan. Med. Bull. 15(7):206–215, 1968.PubMedGoogle Scholar
  44. 44.
    Trout, L., J. T. Gatzy, and S. T. Ballard. Acetylcholine-induced liquid secretion by bronchial epithelium: role of cl- and hco-3 transport. AJP - Lung Cell. Mol. Physiol. 275(6):L1095–L1099, 1998.Google Scholar
  45. 45.
    Trout, L., M. I. Townsley, A. L. Bowden, and S. T. Ballard. Disruptive effects of anion secretion inhibitors on airway mucus morphology in isolated perfused pig lung. J. Physiol. 549(Pt 3):845–853, 2003.CrossRefPubMedGoogle Scholar
  46. 46.
    Tsai, C. L., G. M. Saidel, E. R. McFadden, and J. M. Fouke. Radial heat and water transport across the airway wall. J. Appl. Physiol. 69(1):222–231, 1990.PubMedGoogle Scholar
  47. 47.
    Tsu, M. E., A. L. Babb, D. D. Ralph, and M. P. Hlastala. Dynamics of heat, water, and soluble gas exchange in the human airways: 1. A model study. Ann. Biomed. Eng. 16(6):547–571, 1988.CrossRefPubMedGoogle Scholar
  48. 48.
    Ueki, I., V. F. German, and J. A. Nadel. Micropipette measurement of airway submucosal gland secretion. Autonomic effects. Am. Rev. Respir. Dis. 121(2):351–357, 1980.PubMedGoogle Scholar
  49. 49.
    Valvano, J., J. Allen, and H. F. Bowman. The simultaneous measurement of thermal conductivity, thermal diffusivity, and perfusion in small volumes of tissue. J. Biomech. Eng. 106:192–197, 1984.CrossRefPubMedGoogle Scholar
  50. 50.
    Warren, N. J., M. H. Tawhai, and E. J. Crampin. A mathematical model of calcium-induced fluid secretion in airway epithelium. J. Theor. Biol. 259(4):837–849, 2009.CrossRefPubMedGoogle Scholar
  51. 51.
    Warren, N. J., M. H. Tawhai, and E. J. Crampin. Mathematical modelling of calcium wave propagation in airway epithelium: evidence for regenerative atp release. Exp. Physiol. 95(1):232–249, 2010.CrossRefPubMedGoogle Scholar
  52. 52.
    Weibel, E. R. Morphometry of the Human Lung, 1st ed. Berlin: Springer-Verlag, 1963.Google Scholar
  53. 53.
    Whimster, W. (1986). Number and mean volume of individual submucous glands in the human tracheobronchial tree. Appl. Pathol. 4:24–32, 1986.PubMedGoogle Scholar
  54. 54.
    Widdicombe, J. H. Regulation of the depth and composition of airway surface liquid. J. Anat. 201(4):313–318, 2002.CrossRefPubMedGoogle Scholar
  55. 55.
    Widdicombe, J. H., S. J. Bastacky, D. X. Wu, and C. Y. Lee. Regulation of depth and composition of airway surface liquid. Eur. Respir. J. 10(12):2892–2897, 1997.CrossRefPubMedGoogle Scholar
  56. 56.
    Williams, R. B. The effects of excessive humidity. Respir. Care Clin. N. Am., 4(2):215–228, 1998.PubMedGoogle Scholar
  57. 57.
    Williams, R., N. Rankin, T. Smith, D. Galler, and P. Seakins. Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa. Crit. Care Med. 24(11):1920–1929, 1996.CrossRefPubMedGoogle Scholar
  58. 58.
    Wine, J. J., and N. S. Joo. Submucosal glands and airway defense. Proc. Am. Thorac. Soc. 1(1):47–53, 2004.CrossRefPubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2010

Authors and Affiliations

  1. 1.Auckland Bioengineering InstituteUniversity of AucklandAucklandNew Zealand
  2. 2.Department of Engineering ScienceUniversity of AucklandAucklandNew Zealand

Personalised recommendations