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      Computational lung modelling in respiratory medicine

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          Abstract

          Computational modelling of the lungs is an active field of study that integrates computational advances with lung biophysics, biomechanics, physiology and medical imaging to promote individualized diagnosis, prognosis and therapy evaluation in lung diseases. The complex and hierarchical architecture of the lung offers a rich, but also challenging, research area demanding a cross-scale understanding of lung mechanics and advanced computational tools to effectively model lung biomechanics in both health and disease. Various approaches have been proposed to study different aspects of respiration, ranging from compartmental to discrete micromechanical and continuum representations of the lungs. This article reviews several developments in computational lung modelling and how they are integrated with preclinical and clinical data. We begin with a description of lung anatomy and how different tissue components across multiple length scales affect lung mechanics at the organ level. We then review common physiological and imaging data acquisition methods used to inform modelling efforts. Building on these reviews, we next present a selection of model-based paradigms that integrate data acquisitions with modelling to understand, simulate and predict lung dynamics in health and disease. Finally, we highlight possible future directions where computational modelling can improve our understanding of the structure–function relationship in the lung.

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          Most cited references168

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          HYPSOMETRIC (AREA-ALTITUDE) ANALYSIS OF EROSIONAL TOPOGRAPHY

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            Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.

            Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50). These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used. Copyright 2004 Massachusetts Medical Society
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              The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease.

              The pulmonary extracellular matrix (ECM) determines the tissue architecture of the lung, and provides mechanical stability and elastic recoil, which are essential for physiological lung function. Biochemical and biomechanical signals initiated by the ECM direct cellular function and differentiation, and thus play a decisive role in lung development, tissue remodelling processes and maintenance of adult homeostasis. Recent proteomic studies have demonstrated that at least 150 different ECM proteins, glycosaminoglycans and modifying enzymes are expressed in the lung, and these assemble into intricate composite biomaterials. These highly insoluble assemblies of interacting ECM proteins and their glycan modifications can act as a solid phase-binding interface for hundreds of secreted proteins, which creates an information-rich signalling template for cell function and differentiation. Dynamic changes within the ECM that occur upon injury or with ageing are associated with several chronic lung diseases. In this review, we summarise the available data about the structure and function of the pulmonary ECM, and highlight changes that occur in idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma and lung cancer. We discuss potential mechanisms of ECM remodelling and modification, which we believe are relevant for future diagnosis and treatment of chronic lung disease.
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                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: ResourcesRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Journal
                J R Soc Interface
                J R Soc Interface
                RSIF
                royinterface
                Journal of the Royal Society Interface
                The Royal Society
                1742-5689
                1742-5662
                June 8, 2022
                June 2022
                June 8, 2022
                : 19
                : 191
                : 20220062
                Affiliations
                [ 1 ] Department of Biomedical Engineering, Texas A&M University, , College Station, TX, USA
                [ 2 ] Department of Radiology, Perelman School of Medicine, University of Pennsylvania, , Philadelphia, PA, USA
                [ 3 ] Department of Biomedical Engineering, Tulane University, , New Orleans, LA, USA
                [ 4 ] Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, , Philadelphia, PA, USA
                [ 5 ] Department of Bioengineering, University of Colorado Denver | Anschutz Medical Campus, , Aurora, CO, USA
                [ 6 ] Department of Pediatric Pulmonary and Sleep Medicine, School of Medicine, University of Colorado, , Aurora, CO, USA
                [ 7 ] J. Mike Walker '66 Department of Mechanical Engineering, Texas A&M University, , College Station, TX, USA
                [ 8 ] Department of Cardiovascular Sciences, Houston Methodist Academic Institute, Houston, TX, USA,
                Author information
                http://orcid.org/0000-0002-5445-4070
                http://orcid.org/0000-0001-9787-1117
                Article
                rsif20220062
                10.1098/rsif.2022.0062
                9174712
                35673857
                4da2795e-9fab-43d6-87c9-b54498907e6e
                © 2022 The Authors.

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : January 20, 2022
                : May 3, 2022
                Funding
                Funded by: National Institutes of Health, http://dx.doi.org/10.13039/100000002;
                Award ID: R00HL138288
                Award ID: R01HL151630
                Categories
                1004
                25
                18
                31
                Review Articles
                Review Articles

                Life sciences
                lung biomechanics,computational modelling,lung imaging,lung biophysical models
                Life sciences
                lung biomechanics, computational modelling, lung imaging, lung biophysical models

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