title: Patient-Specific Airway Wall Remodeling in Chronic Lung Disease.
abstract: Chronic lung disease affects more than a quarter of the adult population; yet, the mechanics of the airways are poorly understood. The pathophysiology of chronic lung disease is commonly characterized by mucosal growth and smooth muscle contraction of the airways, which initiate an inward folding of the mucosal layer and progressive airflow obstruction. Since the degree of obstruction is closely correlated with the number of folds, mucosal folding has been extensively studied in idealized circular cross sections. However, airflow obstruction has never been studied in real airway geometries; the behavior of imperfect, non-cylindrical, continuously branching airways remains unknown. Here we model the effects of chronic lung disease using the nonlinear field theories of mechanics supplemented by the theory of finite growth. We perform finite element analysis of patient-specific Y-branch segments created from magnetic resonance images. We demonstrate that the mucosal folding pattern is insensitive to the specific airway geometry, but that it critically depends on the mucosal and submucosal stiffness, thickness, and loading mechanism. Our results suggests that patient-specific airway models with inherent geometric imperfections are more sensitive to obstruction than idealized circular models. Our models help to explain the pathophysiology of airway obstruction in chronic lung disease and hold promise to improve the diagnostics and treatment of asthma, bronchitis, chronic obstructive pulmonary disease, and respiratory failure.
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA. eskandar@stanford.edu.
authors.forename: Mona
authors.initials: M
authors.lastname: Eskandari
authors.affiliation: Medical Service, Veterans Affairs Palo Alto Health Care System, Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, 94305, USA. kuschner@stanford.edu.
authors.forename: Ware G
authors.initials: WG
authors.lastname: Kuschner
authors.affiliation: Departments of Mechanical Engineering, Bioengineering, and Cardiothoracic Surgery, Stanford University, Stanford, CA, 94305, USA. ekuhl@stanford.edu.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kuhl
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D002908:Chronic Disease; D006801:Humans; D008171:Lung Diseases / Q000473:pathology / Q000503:physiopathology*; D008954:Models, Biological; D020545:Respiratory Mucosa / Q000473:pathology / Q000503:physiopathology*
keywords: Airway remodeling; Asthma; Bronchitis; Bronchoconstriction; Chronic lung disease; Finite element analysis; Patient-specific modeling
references.citation: Am J Respir Crit Care Med. 1999 Sep;160(3):968-75
references.pmid: 10471626
references.citation: Am J Respir Crit Care Med. 2000 Jan;161(1):244-8
references.pmid: 10619827
references.citation: J Appl Physiol (1985). 2000 Feb;88(2):527-33
references.pmid: 10658019
references.citation: Respir Med. 2000 Mar;94(3):204-13
references.pmid: 10783930
references.citation: Am J Respir Crit Care Med. 2000 May;161(5):1720-45
references.pmid: 10806180
references.citation: Eur Respir J. 2000 Aug;16(2):349-54
references.pmid: 10968513
references.citation: Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):896-904
references.pmid: 10988102
references.citation: Ann Biomed Eng. 2000 Jul;28(7):793-802
references.pmid: 11016416
references.citation: J Allergy Clin Immunol. 2000 Dec;106(6):1033-42
references.pmid: 11112883
references.citation: Annu Rev Biomed Eng. 1999;1:47-72
references.pmid: 11701482
references.citation: J Appl Physiol (1985). 2002 Mar;92(3):1261-6
references.pmid: 11842066
references.citation: J Biomech Eng. 2002 Aug;124(4):334-41
references.pmid: 12188199
references.citation: Ann Biomed Eng. 2003 Apr;31(4):363-73
references.pmid: 12723678
references.citation: Ann Biomed Eng. 2003 Apr;31(4):374-90
references.pmid: 12723679
references.citation: N Engl J Med. 2004 Jun 24;350(26):2645-53
references.pmid: 15215480
references.citation: Lancet. 2004 Aug 21-27;364(9435):709-21
references.pmid: 15325838
references.citation: Clin Sci (Lond). 2005 Jun;108(6):463-77
references.pmid: 15896192
references.citation: Biomech Model Mechanobiol. 2007 Sep;6(5):321-31
references.pmid: 17119902
references.citation: Chest. 2007 Jan;131(1):20-8
references.pmid: 17218552
references.citation: N Engl J Med. 2007 Mar 8;356(10):1073; author reply 1073
references.pmid: 17347465
references.citation: J Appl Physiol (1985). 1991 Aug;71(2):666-73
references.pmid: 1938740
references.citation: J Biomech. 2009 Jul 22;42(10):1553-9
references.pmid: 19501360
references.citation: J Appl Physiol (1985). 2010 Feb;108(2):401-11
references.pmid: 19910337
references.citation: Respir Res. 2010 Jan 22;11:9
references.pmid: 20092657
references.citation: J Biomech. 2011 Jan 4;44(1):182-8
references.pmid: 20880530
references.citation: J Allergy Clin Immunol. 2011 Jan;127(1):145-52
references.pmid: 21211649
references.citation: J Appl Physiol (1985). 2011 Apr;110(4):1003-12
references.pmid: 21252217
references.citation: Comput Methods Biomech Biomed Engin. 2012;15(5):547-61
references.pmid: 21347909
references.citation: J Mech Phys Solids. 2011 Apr 1;59(4):863-883
references.pmid: 21532929
references.citation: J Appl Physiol (1985). 1990 Sep;69(3):849-60
references.pmid: 2246172
references.citation: Respiration. 2012;84(2):89-97
references.pmid: 22868355
references.citation: Mech Res Commun. 2012 Jun 1;42:1-14
references.pmid: 22919118
references.citation: Curr Opin Pulm Med. 2013 Mar;19(2):109-15
references.pmid: 23325030
references.citation: J R Soc Interface. 2013 Mar 13;10(82):20130109
references.pmid: 23486174
references.citation: J Mech Phys Solids. 2013 Jun 1;61(6):1446-1463
references.pmid: 23606760
references.citation: J Mech Behav Biomed Mater. 2014 Jan;29:594-601
references.pmid: 23768627
references.citation: J Mech Behav Biomed Mater. 2014 Jan;29:20-32
references.pmid: 24041754
references.citation: Ann Biomed Eng. 2014 Jun;42(6):1158-69
references.pmid: 24639211
references.citation: Sci Rep. 2014 Jul 10;4:5644
references.pmid: 25008163
references.citation: J Mech Phys Solids. 2014 Dec 1;72:75-92
references.pmid: 25202162
references.citation: Eur J Mech A Solids. 2014 Nov;48:38-47
references.pmid: 25267880
references.citation: Comput Mech. 2014 Jun;53(6):1183-1196
references.pmid: 25342868
references.citation: J Theor Biol. 2015 Jan 21;365:301-10
references.pmid: 25451524
references.citation: Phys Rev Lett. 2014 Dec 12;113(24):248101
references.pmid: 25541805
references.citation: Biomech Model Mechanobiol. 2015 Oct;14(5):931-65
references.pmid: 25716305
references.citation: Materials (Basel). 2013 Dec 04;6(12):5639-5658
references.pmid: 28788414
references.citation: Am Rev Respir Dis. 1989 Jan;139(1):242-6
references.pmid: 2912345
references.citation: J Appl Physiol (1985). 1988 Jun;64(6):2522-31
references.pmid: 3403436
references.citation: Chest. 1995 Mar;107(3 Suppl):111S-117S
references.pmid: 7874987
references.citation: J Appl Physiol (1985). 1994 Jun;76(6):2627-35
references.pmid: 7928893
references.citation: J Appl Physiol (1985). 1994 Aug;77(2):1011-4
references.pmid: 8002485
references.citation: J Biomech. 1994 Apr;27(4):455-67
references.pmid: 8188726
references.citation: Am Rev Respir Dis. 1993 Nov;148(5):1220-5
references.pmid: 8239157
references.citation: J Appl Physiol (1985). 1997 Dec;83(6):1814-21
references.pmid: 9390950
references.citation: Ann Biomed Eng. 1999 Jan-Feb;27(1):14-22
references.pmid: 9916756