Monitoring lung disease and therapy by rheometry and computer simulations

Overview

Our project is indeed dedicated to the modeling and scientific computing of realistic lung epithelium cells and their surroundingmucus, in order to exhibit two conclusions: check that we have understood the right dominant physics, predict whether a cell+mucus set is pathological or not, and follow quantitatively its evolution, applied to therapymonitoring.

From BioFiReaDy to MucoReaDy: proofs of concepts

This project has started with the numerical study of a biofilm surrounding a ciliated cell, featuring the lung wall. Originally, the ANR JCJC project BioFiReaDy has built a formulation of variable viscosity flows at the micrometer scale of an ideal ciliated cell of the lung. This has been extended to shear-thinning fluids and complemented by experimental collection of Intensity/Index values of CF patients at CHU Toulouse-Larrey. This has led to the questions and challenges raised in the present project MucoReaDy, displayed at the bottom right corner.

On the map generated by computer simulation, the first patient studied has moved from low to normal mucociliary clearance between the day 1 of his therapeutic care and three weeks later, at CHU Toulouse-Larrey.

Accurate computer simulation shows if the dominant phenomena are correctly quantified, understood and well modeled. This way, the parameters featuring the model can be easily modified and their impacts on pathologies and therapies can be investigated.

MucoReaDy will be at the Interpore2025 conference (Albuquerque, NM, USA)

J-M. Etancelin, M. Murris-Espin, S. Bui, S. Mallah, M. Fayon, P. Poncet, Motion by beating of porous biofilms with heterogeneous rheology: Simulation and clinical assessment of therapy for cystic fibrosis, Symposium MS21, Interpore 2025 conference, Albuquerque, USA (2025).

Publications and communications

S. Perez, S. Maddu, I. Sbalzarini, P. Poncet, Adaptive weighting of Bayesian physics informed neural networks for multitask and multiscale forward and inverse problems, Journal of Computational Physics 491, pp.112342 (2023).

Licence CC-BY-NC-ND: http://arxiv.org/abs/2302.12697 , https://hal.science/hal-04011497 et Elsevier JCP

J-M. Etancelin, M. Murris-Espin, P. Poncet, Particle methods for the dynamics of porous biofilms with heterogeneous rheology and its interaction with human lung epithelium, InterPore 2023 – MS05, Edinburgh, Scotland (2023).
S. Perez, P. Poncet, Chemical and morphological uncertainty quantification by auto-weighted Bayesian Physics-Informed Neural Networks for reactive two-scale porous media at the pore scale, InterPore 2023 – MS14, Edinburgh, Scotland (2023).
P. Poncet, Numerical simulation of biological films and respiratory epithelium for therapy monitoring, Journée BioMimDay, Anglet, France (2022).
P. Poncet, Particle methods for pore-scale modeling of reactive and rheological flows, Séminaire ISIFoR-IFPEN, Pau, France (2022).

Past publications of the team

N. Baït, B. Grassl, C. Derail, and A. Benaboura, Hydrogel nanocomposites as pressure-sensitive adhesives for skin-contact applications, Soft Matter 7, 2025-2032 (2011).
S. Baklouti, C. Massip, C. Mane, H. Guet-Revillet, M. Murris-Espin, D. Concordet, P. Gandia, Comment on: In vitro activity of seven 𝛽-lactams including ceftolozane/tazobactam and ceftazidime/avibactam against Burkholderia cepacia complex, Burkholderia gladioli and other non-fermentative Gram-negative bacilli isolated from cystic fibrosis patients, J Antimicrob Chemother. 74(10), 3122-3123 (2019).
C. Barthe, S. Nandakumar, L. Derlich, J. Macey, S. Bui, M. Fayon, M. Crouzet, B. Garbay, S. Vilain, P. Costaglioli, Exploring the expression of Pseudomonas aeruginosa genes directly from sputa of cystic fibrosis patients, Lett. Appl. Microbiol. 61(5), 423-428 (2015).
S. Bui, V. Boisserie-Lacroix, F. Ceccato, H. Clouzeau, S. Debelleix, M. Fayon, L’inflammation pulmonaire dans la mucoviscidose, Elsevier Masson, Archives de Pédiatrie 19, S8-S12 (2012).
P. R. Burgel, A. Munck, I. Durieu, R. Chiron, L. Mely, A. Prevotat, M. Murris-Espin, M. Porzio, M. Abely, P. Reix, C. Marguet, J. Macey, I. Sermet-Gaudelus, H. Corvol, S. Bui, L. Lemonnier, C. Dehillotte, J. Da Silva, J-L. Paillasseur, D. Hubert, French Cystic Fibrosis Reference Network Study Group, Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis, Am. J. Respir. Crit. Care Med. (2020).
R. Chatelin, D. Anne-Archard, M. Murris-Espin, M. Thiriet, P. Poncet, Numerical and experimental investigation of mucociliary clearance breakdown in cystic fibrosis, J. Biomech. 53, 56-63 (2017).
R. Chatelin, D. Anne-Archard, M. Murris-Espin, D. Sanchez, M. Thiriet, A. Didier, P. Poncet, Modelling Cystic Fibrosis and Mucociliary Clearance, in Microscale Transport Modelling in Biological Processes, Elsevier Inc. (2017).
R. Chatelin and P. Poncet, A parametric study of mucociliary transport by numerical simulations of 3D non-homogeneous mucus, J. Biomech. 49, 1772-1780 (2016).
R. Chatelin, D. Sanchez and P. Poncet, Analysis of penalized variable viscosity 3D Stokes equations coupled with transport and diffusion, ESAIM: Math. Model. Numer. Anal. 50(2), 565-591 (2016).
R. Chatelin, P. Poncet, A. Didier, M. Murris-Espin, D. Anne-Archard and M. Thiriet, Mucus and ciliated cells of human lung: splitting strategies for particle methods and 3D Stokes flows, Procedia IUTAM 18, 114-122 (2015).
R. Chatelin, P. Poncet, Hybrid grid-particle methods and Pen alization : A Sherman-Morrison-Woodbury approach to compute 3D viscous flows using FFT, J. Comp. Phys. 269, 314–328 (2014).
R. Chatelin, P. Poncet, A hybrid grid-particle method for moving bodies in a 3D Stokes flow with variable viscosity, SIAM J. Sci. Comp. 35(4), B925–B949 (2013).
G-H. Cottet, J.-M. Etancelin, F. Perignon and C. Picard, High order semi-lagrangian particles for transport equations: numerical analysis and implementations issues, M2AN 48 (2014).
G. Dournes, P. Berger, J. Refait, J. Macey, S. Bui, L. Delhaes, M. Montaudon, O. Corneloup, JF. Chateil, R. Marthan, M. Fayon, F. Laurent, Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis: MR Imaging of Airway Mucus Contrasts as a Tool for Diagnosis, Radiology 285(1), 261-269 (2017).
S. Enault, D. Lombardi, P. Poncet and M. Thiriet, Mucus dynamics subject to air and wall motion, ESAIM Proc. 30, 125–141 (2010).
M. Murris-Espin, A. Didier, Cystic fibrosis : from infancy to adulthood, Chronic infection and education, Rev. Mal. Respir. 22, 3 (2005).
B. Noetinger, L. Hume, R. Chatelin, P. Poncet, Effective viscosity of a random mixture of fluids, Phys. Rev. Fluids 3, 014103 (2018).
P. Poncet, Finite difference stencils based on particle strength exchange schemes for improvement of vortex methods, J. Turbulence 7:N23 (2006).
R. Nové-Josserand, S. Grard, L. Auzou, P. Reix, M. Murris-Espin, F. Brémont, B. Mammar, L. Mely, D. Hubert, I. Durieu, P. R. Burgel, Case series of omalizumab for allergic bronchopulmonary aspergillosis in cystic fibrosis patients, Pediatr. Pulmonol. 52(2), 190-197 (2017).
B. R. M. Perrin, M. Braccini, C. M. Bidan, C. Derail, E. Papon, Y. Leterrier, Y. Barrandon, Adhesion of surgical sealants used in cardiothoracic and vascular surgery, Int. J. Adhesion Adhesives, 70, 81–89, 2016
J. Refait, J. Macey, S. Bui, M. Fayon, P. Berger, L. Delhaes, F. Laurent, G. Dournes, CT evaluation of hyperattenuating mucus to diagnose allergic bronchopulmonary aspergillosis in the special condition of cystic fibrosis, J. Cyst. Fibros. 18(4), e31-e36 (2019).
J. Renvoise, D. Burlot, G. Marin, C. Derail, Adherence performances of Pressure Sensitive Adhesives on a model viscoelastic synthetic film : a tool for the understanding of adhesion on the human skin, Int. J. Pharma. 368, 83-88 (2009).
D. Sanchez, L. Hume, R. Chatelin, P. Poncet, Analysis of non-linear Stokes problem coupled to transport-diffusion for shear-thinning heterogeneous microscale flows, applications to digital rock physics and mucociliary clearance, ESAIM: Math. Model. Numer. Anal. 53, 1083–1124 (2019, open access).

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