Abstract

Diffuse alveolar damage (DAD) is a characteristic histopathologic pattern in most cases of acute respiratory distress syndrome and severe viral pneumonia, such as COVID-19. DAD is characterized by an acute phase with edema, hyaline membranes, and inflammation followed by an organizing phase with pulmonary fibrosis and hyperplasia. The degree of pulmonary fibrosis and surface tension is different in the pathological stages of DAD. The effects of pulmonary fibrosis and surface tension on alveolar sac mechanics in DAD are investigated by using the fluid–structure interaction (FSI) method. The human pulmonary alveolus is idealized by a three-dimensional honeycomb-like geometry, with alveolar geometries approximated as closely packed 14-sided polygons. A dynamic compression-relaxation model for surface tension effects is adopted. Compared to a healthy model, DAD models are created by increasing the tissue thickness and decreasing the concentration of the surfactant. The FSI results show that pulmonary fibrosis is more influential than the surface tension on flow rate, volume, P–V loop, and resistance. The lungs of the disease models become stiffer than those of the healthy models. According to the P–V loop results, the surface tension plays a more important role in hysteresis than the material nonlinearity of the lung tissue. Our study demonstrates the differences in air flow and lung function on the alveolar sacs between the healthy and DAD models.

References

1.
Konopka
,
K. E.
,
Nguyen
,
T.
,
Jentzen
,
J. M.
,
Rayes
,
O.
,
Schmidt
,
C. J.
,
Wilson
,
A. M.
,
Farver
,
C. F.
, and
Myers
,
J. L.
,
2020
, “
Diffuse Alveolar Damage (DAD) Resulting From Coronavirus Disease 2019 Infection is Morphologically Indistinguishable From Other Causes of DAD
,”
Histopathology
,
77
(
4
), pp.
570
578
.10.1111/his.14180
2.
Katzenstein, A.-L
,
A.
,
Bloor
,
C. M.
, and
Leibow
,
A. A.
,
1976
, “Diffuse Alveolar Damage- Role Oxygen, Shock,”
Relat. Factors
,
85
(
1
), p.
20
.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032554/
3.
West
,
J. B.
,
2012
,
Respiratory Physiology: The Essentials
,
Lippincott Williams & Wilkins
, San Diego, CA.
4.
Saad
,
S. M. I.
,
Neumann
,
A. W.
, and
Acosta
,
E. J.
,
2010
, “
A Dynamic Compression–Relaxation Model for Lung Surfactants
,”
Colloids Surf. A: Physicochem. Eng. Aspects
,
354
(
1–3
), pp.
34
44
.10.1016/j.colsurfa.2009.07.046
5.
Han
,
S.
, and
Mallampalli
,
R. K.
,
2015
, “
The Role of Surfactant in Lung Disease and Host Defense Against Pulmonary Infections
,”
Ann. Am. Thorac. Soc.
,
12
(
5
), pp.
765
774
.10.1513/AnnalsATS.201411-507FR
6.
Aghasafari
,
P.
,
Heise
,
R. L.
,
Reynolds
,
A.
, and
Pidaparti
,
R. M.
,
2019
, “
Aging Effects on Alveolar Sacs Under Mechanical Ventilation
,”
J. Gerontol. Ser. A
,
74
(
2
), pp.
139
146
.10.1093/gerona/gly097
7.
Pidaparti
,
R. M.
,
Burnette
,
M.
,
Heise
,
R. L.
, and
Reynolds
,
A.
,
2013
, “
Analysis for Stress Environment in the Alveolar Sac Model
,”
J. Biomed. Sci. Eng.
,
06
(
09
), pp.
901
907
.10.4236/jbise.2013.69110
8.
Xia
,
G.
,
Tawhai
,
M. H.
,
Hoffman
,
E. A.
, and
Lin
,
C.-L.
,
2010
, “
Airway Wall Stiffening Increases Peak Wall Shear Stress: A Fluid–Structure Interaction Study in Rigid and Compliant Airways
,”
Ann. Biomed. Eng.
,
38
(
5
), pp.
1836
1853
.10.1007/s10439-010-9956-y
9.
Monjezi
,
M.
, and
Saidi
,
M. S.
,
2016
, “
Fluid-Structure Interaction Analysis of Air Flow in Pulmonary Alveoli During Normal Breathing in Healthy Humans
,”
Sci. Iran.
,
23
(
4
), pp.
1826
1836
.10.24200/sci.2016.3929
10.
Oakes
,
J. M.
,
Hofemeier
,
P.
,
Vignon-Clementel
,
I. E.
, and
Sznitman
,
J.
,
2016
, “
Aerosols in Healthy and Emphysematous in Silico Pulmonary Acinar Rat Models
,”
J. Biomech.
,
49
(
11
), pp.
2213
2220
.10.1016/j.jbiomech.2015.11.026
11.
Oakes
,
J. M.
,
Day
,
S.
,
Weinstein
,
S. J.
, and
Robinson
,
R. J.
,
2010
, “
Flow Field Analysis in Expanding Healthy and Emphysematous Alveolar Models Using Particle Image Velocimetry
,”
ASME J. Biomech. Eng.
,
132
(
2
), p.
021008
.10.1115/1.4000870
12.
Dutta
,
A.
,
Vasilescu
,
D. M.
,
Hogg
,
J. C.
,
Phillion
,
A. B.
, and
Brinkerhoff
,
J. R.
,
2018
, “
Simulation of Airflow in an Idealized Emphysematous Human Acinus
,”
ASME J. Biomech. Eng.
,
140
(
7
), p.
071001
.10.1115/1.4039680
13.
Chen
,
L.
, and
Zhao
,
X.
,
2019
, “
Characterization of Air Flow and Lung Function in the Pulmonary Acinus by Fluid-Structure Interaction in Idiopathic Interstitial Pneumonias
,”
PLoS ONE
,
14
(
3
), p.
e0214441
.10.1371/journal.pone.0214441
14.
Haefeli-Bleuer
,
B.
, and
Weibel
,
E. R.
,
1988
, “
Morphometry of the Human Pulmonary Acinus
,”
Anatom. Rec.
,
220
(
4
), pp.
401
414
.10.1002/ar.1092200410
15.
Heistracher
,
T.
, and
Hofmann
,
W.
,
1995
, “
Physiologically Realistic Models of Bronchial Airway Bifurcations
,”
J. Aerosol Sci.
,
26
(
3
), pp.
497
509
.10.1016/0021-8502(94)00113-D
16.
Yeh
,
H.
, and
Schum
,
G.
,
1980
, “
Models of Human Lung Airways and Their Application to Inhaled Particle Deposition
,”
Bull. Math. Biol.
,
42
(
3
), pp.
461
480
.10.1016/S0092-8240(80)80060-7
17.
Kim
,
J.
,
Heise
,
R. L.
,
Reynolds
,
A. M.
, and
Pidaparti
,
R. M.
,
2017
, “
Aging Effects on Airflow Dynamics and Lung Function in Human Bronchioles
,”
PLos One
,
12
(
8
), p.
e0183654
.10.1371/journal.pone.0183654
18.
Verbeken
,
E. K.
,
Cauberghs
,
M.
,
Mertens
,
I.
,
Clement
,
J.
,
Lauweryns
,
J. M.
, and
Van de Woestijne
,
K. P.
,
1992
, “
The Senile Lung. Comparison With Normal and Emphysematous Lungs. 1. Structural Aspects
,”
Chest
,
101
(
3
), pp.
793
799
.10.1378/chest.101.3.793
19.
Lai-Fook
,
S. J.
, and
Hyatt
,
R. E.
,
2000
, “
Effects of Age on Elastic Moduli of Human Lungs
,”
J. Appl. Physiol.
,
89
(
1
), pp.
163
168
.10.1152/jappl.2000.89.1.163
20.
Tian
,
S.
,
Hu
,
W.
,
Niu
,
L.
,
Liu
,
H.
,
Xu
,
H.
, and
Xiao
,
S.-Y.
,
2020
, “
Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer
,”
J. Thorac. Oncol.
,
15
(
5
), pp.
700
704
.10.1016/j.jtho.2020.02.010
21.
Calabrese
,
F.
,
Pezzuto
,
F.
,
Fortarezza
,
F.
,
Hofman
,
P.
,
Kern
,
I.
,
Panizo
,
A.
,
von der Thüsen
,
J.
,
Timofeev
,
S.
,
Gorkiewicz
,
G.
, and
Lunardi
,
F.
,
2020
, “
Pulmonary Pathology and COVID-19: Lessons From Autopsy. The Experience of European Pulmonary Pathologists
,”
Virchows Arch
,
477
(
3
), pp.
359
372
.10.1007/s00428-020-02886-6
22.
Domino
,
S.
,
2015
,
Sierra Low Mach Module: Nalu Theory Manual 1.0
, Albuquerque, NM, Report No. SAND2015-3107W.
23.
Edwards
,
H.
,
Williams
,
A.
,
Sjaardema
,
G.
,
Baur
,
D.
, and
Cochran
,
W.
,
2010
,
SIERRA Toolkit Computational Mesh Computational Model
, Albuquerque, NM, SAND2010-1192.
24.
Long
,
K. R.
,
Tuminaro
,
R. S.
,
Bartlett
,
R. A.
,
Hoekstra
,
R. J.
,
Phipps
,
E. T.
,
Kolda
,
T. G.
,
Lehoucq
,
R. B.
,
Thornquist
,
H. K.
,
Hu
,
J. J.
,
Williams
,
A. B.
,
Salinger
,
A. G.
,
Howle
,
V. E.
,
Pawlowski
,
R. P.
,
Willenbring
,
J. M.
, and
Heroux
,
M. A.
,
2003
,
An Overview of Trilinos
, SAND2003-2927.
25.
Zienkiewicz
,
O. C.
, and
Taylor
,
R. L.
,
2013
,
The Finite Element Method
, 7th ed.,
Elsevier
,
Oxford, UK
.
26.
Li
,
X. S.
, and
Demmel
,
J. W.
,
2003
, “
SuperLU_DIST: A Scalable Distributed-Memory Sparse Direct Solver for Unsymmetric Linear Systems
,”
ACM Trans. Math. Softw.
,
29
(
2
), pp.
110
140
.10.1145/779359.779361
27.
Sznitman
,
J.
,
Heimsch
,
F.
,
Heimsch
,
T.
,
Rusch
,
D.
, and
Rösgen
,
T.
,
2007
, “
Three-Dimensional Convective Alveolar Flow Induced by Rhythmic Breathing Motion of the Pulmonary Acinus
,”
ASME J. Biomech. Eng.
,
129
(
5
), pp.
658
665
.10.1115/1.2768109
28.
Hofemeier
,
P.
, and
Sznitman
,
J.
,
2014
, “
Role of Alveolar Topology on Acinar Flows and Convective Mixing
,”
ASME J. Biomech. Eng.
,
136
(
6
), p.
061007
.10.1115/1.4027328
29.
Pantelidis
,
P.
, and
Veeraraghavan
,
S.
,”
Surfactant Gene Polymorphisms and Interstitial Lung Diseases
,” Respir. Res.,
3
(
1
), p.
7
.10.1186/rr163
30.
Schousboe
,
P.
,
Wiese
,
L.
,
Heiring
,
C.
,
Verder
,
H.
,
Poorisrisak
,
P.
,
Verder
,
P.
, and
Nielsen
,
H. B.
,
2020
, “
Assessment of Pulmonary Surfactant in COVID-19 Patients
,”
Crit. Care
,
24
(
1
), p.
552
.10.1186/s13054-020-03268-9
31.
Rendall
,
T. C. S.
, and
Allen
,
C. B.
,
2009
, “
Efficient Mesh Motion Using Radial Basis Functions With Data Reduction Algorithms
,”
J. Comput. Phys.
,
228
(
17
), pp.
6231
6249
.10.1016/j.jcp.2009.05.013
32.
Chen
,
L.
, and
Zhao
,
X.
,
2019
, “
Surface Tension Effects on Pulmonary Acinus Mechanics in Idiopathic Pulmonary Fibrosis Patients
,”
Basic Clin. Pharmacol. Toxicol.
,
125
(
5, SI
), pp.
36
37
.
33.
Kolanjiyil
,
A. V.
, and
Kleinstreuer
,
C.
,
2017
, “
Computational Analysis of Aerosol-Dynamics in a Human Whole-Lung Airway Model
,”
J. Aerosol Sci.
,
114
, pp.
301
316
.10.1016/j.jaerosci.2017.10.001
34.
Denny
,
E.
, and
Schroter
,
R. C.
,
1997
, “
Relationships Between Alveolar Size and Fibre Distribution in a Mammalian Lung Alveolar Duct Model
,”
ASME J. Biomech. Eng.
,
119
(
3
), pp.
289
297
.10.1115/1.2796093
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