Speaker
Description
Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent lung disease characterized by alveolar wall damage, leading to progressive loss of lung function\cite{1}. Lymphangioleimyostasis (LAM), a rare respiratory disease, is also characterised by lung tissue destruction, but also by the growth of abnormal smooth muscle-like cells\cite{2}. The interactions between injury and abnormal repair leading to damage are not well understood. In both diseases, tissue destruction is driven by protease secretion due to complex interactions between immune and structural cells and proteins, during injury and abnormal repair processes. This impacts collagen and elastin density in lung tissue, resulting in alveolar wall thinning and eventual destruction. To investigate these mechanisms, we model evolution of tissue constituents and integrity using a system of coupled ordinary differential equations, coupled to the mechanical strain/tension experienced by springs within a 2D elastic spring network\cite{3} representing the alveolar structure in parenchymal tissue\cite{4}. As tissue integrity decreases, any increase in strains exceeding a physiological threshold leads to springs breaking (i.e., tissue damage). Our model, coupled with clinical images and spatial omics data, will allow us to investigate tissue destruction in LAM and COPD and provide time-dependent network-level measures, from which potential biomarkers could be derived.
Bibliography
@article{1,
title={Epidemiology of COPD},
author={Raherison, Chantal and Girodet, PIERRE-OLIVIER},
journal={European respiratory review},
volume={18},
number={114},
pages={213--221},
year={2009},
publisher={European Respiratory Society}
}
@article{2,
title={Cathepsin K in lymphangioleiomyomatosis: LAM cell--fibroblast interactions enhance protease activity by extracellular acidification},
author={Dongre, Arundhati and Clements, Debbie and Fisher, Andrew J and Johnson, Simon R},
journal={The American journal of pathology},
volume={187},
number={8},
pages={1750--1762},
year={2017},
publisher={Elsevier}
}
@article{3,
title={A personalized spring network representation of emphysematous lungs from CT images},
author={Yuan, Ziwen and Herrmann, Jacob and Murthy, Samhita and Peters, Kevin and Gerard, Sarah E and Nia, Hadi T and Lutchen, Kenneth R and Suki, B{\'e}la},
journal={Frontiers in Network Physiology},
volume={2},
pages={828157},
year={2022},
publisher={Frontiers Media SA}
}
@article{4,
title={Coupled immunological and biomechanical model of emphysema progression},
author={Ceresa, Mario and Olivares, Andy L and Noailly, J{\'e}r{\^o}me and Gonz{\'a}lez Ballester, Miguel A},
journal={Frontiers in physiology},
volume={9},
pages={388},
year={2018},
publisher={Frontiers Media SA}
}
