0
Research Papers

Simulation of Forced Expiration in a Biophysical Model, With Homogeneous and Clustered Bronchoconstriction

[+] Author and Article Information
Kerry L. Hedges

Auckland Bioengineering Institute,
University of Auckland,
Private Bag 92019,
Auckland 1142,
New Zealand
e-mail: k.hedges@auckland.ac.nz

Merryn H. Tawhai

Auckland Bioengineering Institute,
University of Auckland,
Private Bag 92019,
Auckland 1142,
New Zealand
e-mail: m.tawhai@auckland.ac.nz

1Corresponding author.

Manuscript received August 12, 2015; final manuscript received April 6, 2016; published online May 9, 2016. Assoc. Editor: Tim David.

J Biomech Eng 138(6), 061008 (May 09, 2016) (10 pages) Paper No: BIO-15-1404; doi: 10.1115/1.4033475 History: Received August 12, 2015; Revised April 06, 2016

One limitation of forced spirometry is that it integrates the contribution of the complex and dynamic behavior of all of the airways and tissue of the lung into a single exhaling unit, hence, it is not clear how spirometric measures are affected by local changes to the airways or tissue such as the presence of “ventilation defects.” Here, we adapt a wave-speed limitation model to a spatially distributed and anatomically based airway tree that is embedded within a deformable parenchyma, to simulate forced expiration in 1 s (FEV1). This provides a model that can be used to assess the consequence of imposed constrictions on FEV1. We first show how the model can be parameterized to represent imaging and forced spirometry data from nonasthmatic healthy young adults. We then compare the effect of homogeneous and clustered bronchoconstriction on FEV1 in six subject-specific models (three male and three female). The model highlights potential sources of normal subject variability in response to agonist challenge, including the interaction between sites of airway constriction and sites of flow limitation at baseline. The results support earlier studies which proposed that the significant constriction of nondefect airways must be present in order to match to clinical measurements of lung function.

FIGURES IN THIS ARTICLE
<>
Copyright © 2016 by ASME
Your Session has timed out. Please sign back in to continue.

References

de Lange, E. E. , Altes, T. A. , Patrie, J. T. , Gaare, J. D. , Knake, J. J. , Mugler, J. P., III , and Platts-Mills, T. A. , 2006, “ Evaluation of Asthma With Hyperpolarized Helium-3 MRI: Correlation With Clinical Severity and Spirometry,” Chest, 130(4), pp. 1055–1062. [CrossRef] [PubMed]
Tzeng, Y. , Lutchen, K. , and Albert, M. , 2009, “ The Difference in Ventilation Heterogeneity Between Asthmatic and Healthy Subjects Quantified by Using Hyperpolarized 3 He MRI,” J. Appl. Physiol., 106(3), pp. 813–822. [CrossRef] [PubMed]
Costella, S. , Kirby, M. , Maksym, G. , McCormack, D. , Paterson, N. , and Parraga, G. , 2012, “ Regional Pulmonary Response to a Methacholine Challenge Using Hyperpolarized 3He Magnetic Resonance Imaging,” Respirology, 17(8), pp. 1237–1246. [CrossRef] [PubMed]
Anafi, R. , Beck, K. , and Wilson, T. , 2003, “ Impedence, Gas Mixing, and Bimodal Ventilation in Constricted Lungs,” J. Appl. Physiol., 94(3), pp. 1003–1011. [CrossRef] [PubMed]
Venegas, J. G. , Winkler, T. , Musch, G. , Vidal Melo, M. F. , Layfield, D. , Tgavalekos, N. , Fischman, A. J. , Callahan, R. J. , Bellani, G. , and Harris, R. S. , 2005, “ Self-Organized Patchiness in Asthma as a Prelude to Catastrophic Shifts,” Nature, 434(7034), pp. 777–782. [CrossRef] [PubMed]
Lambert, R. K. , Wilson, T. A. , Hyatt, R. E. , and Rodarte, J. R. , 1982, “ A Computational Model for Expiratory Flow,” J. Appl. Physiol., 52(1), pp. 44–56.
Weibel, E. R. , 1963, Morphometry of the Human Lung, Springer-Verlag, Berlin.
Polak, A. , and Lutchen, K. , 2003, “ Computational Model for Forced Expiration From Asymmetrical Normal Lungs,” Ann. Biomed. Eng., 31(8), pp. 891–907. [CrossRef] [PubMed]
Horsfield, K. , Dart, G. , Olson, D. E. , Filley, G. F. , and Cumming, G. , 1971, “ Models of the Human Bronchial Tree,” J. Appl. Physiol., 31, pp. 207–217. [PubMed]
Pardaens, P. , Van De Woestijne, K. , and Clement, J. , 1972, “ A Physical Model of Expiration,” J. Appl. Physiol., 33(4), pp. 479–490. [PubMed]
Solway, J. , Fredberg, J. , Ingram, R., Jr. , Pedersen, O. , and Drazen, J. , 1987, “ Interdependent Regional Lung Emptying During Forced Expiration: A Transistor Model,” J. Appl. Physiol., 62(5), pp. 2013–2025. [PubMed]
Abboud, S. , Barnea, O. , Guber, A. , Narkiss, N. , and Bruderman, I. , 1995, “ Maximum Expiratory Flow-Volume Curve: Mathematical Model and Experimental Results,” Med. Eng. Phys., 17(5), pp. 332–336. [CrossRef] [PubMed]
Tgavalekos, N. , Tawhai, M. , Harris, R. , Mush, G. , Vidal-Melo, M. , Venegas, J. , and Lutchen, K. , 2005, “ Identifying Airways Responsible for Heterogeneous Ventilation and Mechanical Dysfunction in Asthma: An Image Functional Modeling Approach,” J. Appl. Physiol., 99(6), pp. 2388–2397. [CrossRef] [PubMed]
Mitchell, J. H. , Hoffman, E. A. , and Tawhai, M. H. , 2012, “ Relating Indices of Inert Gas Washout to Localised Bronchoconstriction,” Respir. Physiol. Neurobiol., 183(3), pp. 224–233. [CrossRef] [PubMed]
Tawhai, M. H. , Hunter, P. J. , Tschirren, J. , Reinhardt, J. M. , McLennan, G. , and Hoffman, E. A. , 2004, “ CT-Based Geometry Analysis and Finite Element Models of the Human and Ovine Bronchial Tree,” J. Appl. Physiol., 97(6), pp. 2310–2321. [CrossRef] [PubMed]
Hart, M. , Orzalesi, M. , and Crook, C. D. , 1963, “ Relation Between Anatomic Respiratory Dead Space and Body Size and Lung Volume,” J. Appl. Physiol., 18(3), pp. 519–522.
Dawson, S. V. , and Elliot, E. A. , 1977, “ Wave-Speed Limitation on Expiratory Flow—A Unifying Concept,” J. Appl. Physiol., 43(3), pp. 498–515.
Reynolds, D. , and Lee, J. , 1981, “ Steady Pressure-Flow Relationship of a Model of the Canine Bronchial Tree,” J. Appl. Physiol., 51(5), pp. 1072–1079.
Polak, A. , 1998, “ A Forward Model for Maximum Expiration,” Comput. Biol. Med., 28(6), pp. 613–625. [CrossRef] [PubMed]
Tawhai, M. , Nash, N. , Lin, C. , and Hoffman, E. , 2009, “ Supine and Prone Differences in Regional Lung Density and Pleural Pressure Gradients in the Human Lung With Constant Shape,” J. Appl. Physiol., 107(3), pp. 912–920. [CrossRef] [PubMed]
Fung, Y. C. , 1990, Biomechanics: Motion, Flow, Stress, Growth, Springer-Verlag, New York.
Tzelepis, G. , Pavleas, I. , Altarifi, A. , Omran, Q. , and McCool, D. , 2005, “ Expiratory Effort Enhancement and Peak Expiratory Flow in Humans,” Eur. J. Appl. Physiol., 94(1), pp. 11–16. [CrossRef] [PubMed]
Tantucci, C. , Duguet, A. , Giampiccolo, P. , Similowski, T. , Zelter, M. , and Derenne, J. , 2002, “ The Best Peak Expiratory Flow is Flow-Limited and Effort-Independent in Normal Subjects,” Am. J. Respir. Crit. Care Med., 165(9), pp. 1304–1308. [CrossRef] [PubMed]
Busacker, A. , Newell, J. D., Jr. , Keefe, T. , Hoffman, E. A. , Granroth, J. C. , Castro, M. , Fain, S. , and Wenzel, S. , 2009, “ A Multivariate Analysis of Risk Factors for the Air-Trapping Asthmatic Phenotype as Measured by Quantitative CT Analysis,” Chest, 135(1), pp. 48–56. [CrossRef] [PubMed]
Hankinson, J. L. , Odencrantz, J. R. , and Fedan, K. B. , 1999, “ Spirometric Reference Values From a Sample of the General U.S. Population,” Am. J. Respir. Crit. Care Med., 159(1), pp. 179–187. [CrossRef] [PubMed]
American Thoracic Society, 2000, “ Guidelines for Methacholine and Exercise Challenge Testing—1999,” Am. J. Respir. Crit. Care Med., 161(1), pp. 309–329. [CrossRef] [PubMed]
Chung, K. F. , Wenzel, S. E. , Brozek, J. L. , Bush, A. , Castro, M. , Sterk, P. J. , Adcock, I. M. , Bateman, E. D. , Bel, E. H. , Bleecker, E. R. , Boulet, L. P. , Brightling, C. , Chanez, P. , Dahlen, S. E. , Djukanovic, R. , Frey, U. , Gaga, M. , Gibson, P. , Hamid, Q. , Jajour, N. N. , Mauad, T. , Sorkness, R. L. , and Teague, W. G. , 2014, “ International ERS/ATS Guidelines on Definition, Evaluation and Treatment of Severe Asthma,” Eur. Respir. J., 43(2), pp. 343–373. [CrossRef] [PubMed]
Heil, M. , Hazel, A. L. , and Smith, J. A. , 2008, “ The Mechanics of Airway Closure,” Respir. Physiol. Neurobiol., 163(1–3), pp. 214–221. [CrossRef] [PubMed]
Miller, M. R. , Hankinson, J. , Brusasco, V. , Burgos, F. , Casaburi, R. , Coates, A. , Crapo, R. , Enright, P. , van der Grinten, C. P. , Gustafsson, P. , Jensen, R. , Johnson, D. C. , MacIntyre, N. , McKay, R. , Navajas, D. , Pedersen, O. F. , Pellegrino, R. , Viegi, G. , Wanger, J. , and Force, A. E. T. , 2005, “ Standardisation of Spirometry,” Eur. Respir. J., 26(2), pp. 319–338. [CrossRef] [PubMed]
Pedley, T. J. , 1977, “ Pulmonary Fluid Dynamics,” Annu. Rev. Fluid Dyn., 9(1), pp. 229–274. [CrossRef]
Schroter, R. , and Sudlow, M. , 1969, “ Flow Patterns in Models of the Human Bronchial Airways,” Respir. Physiol., 7(3), pp. 341–355. [CrossRef] [PubMed]

Figures

Grahic Jump Location
Fig. 1

Illustration of sites of clustered bronchoconstriction in subject F1. Constricted airways are shown in green. (a) six small clusters per lung and (b) two large clusters per lung.

Grahic Jump Location
Fig. 2

Simulated MEFV (maximum flow against expired volume) curves for normal young adult female (left-hand column) and male (right-hand column) subjects. Individual subject measurements of PEF and FVC are superimposed.

Grahic Jump Location
Fig. 3

Simulated results for expired volume against time for normal young adult female (left-hand column) and male (right-hand column) subjects. Individual subject measurements of FEV1 and FEF25–75 are superimposed.

Grahic Jump Location
Fig. 4

Airway resistance (Raw) normalized by its baseline value against FEV1 for homogeneous airway constriction in all the subjects. (a) shows the simulated FEV1 postconstriction normalized by the FEV1 simulated at baseline and (b) shows the simulated FEV1 postconstriction normalized by the subject's predicted value (based on their demographic data).

Grahic Jump Location
Fig. 5

Calculated sites of flow limitation in all the subjects at PEF. Clusters of same colored airways indicate regions that are distal to a flow limited airway. The color scale indicates the trachea (whole lung) flow at which the limited airway reached its maximum flow.

Grahic Jump Location
Fig. 6

Illustration of effect of variation in pressure at the bifurcations. Solid line shows results using average pressure at each bifurcation in airway tree. Dashed lines show results for ten solutions carried out using pressure values randomly chosen between maximum and minimum pressure entering each bifurcation.

Tables

Errata

Discussions

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In