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| Home > Articles > Published articles > Modelling the dynamics of tuberculosis lesions in a virtual lung : |
(Universitat Politècnica de Catalunya. Departament de Física) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Universitat Politècnica de Catalunya. Departament de Física) (Universitat Politècnica de Catalunya. Departament de Física) (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Universitat Politècnica de Catalunya. Departament de Física)
| Date: | 2020 |
| Abstract: | Tuberculosis (TB) is an infectious disease that still causes more than 1. 5 million deaths annually. The World Health Organization estimates that around 30% of the world's population is latently infected. However, the mechanisms responsible for 10% of this reserve (i. e. , of the latently infected population) developing an active disease are not fully understood, yet. The dynamic hypothesis suggests that endogenous reinfection has an important role in maintaining latent infection. In order to examine this hypothesis for falsifiability, an agent-based model of growth, merging, and proliferation of TB lesions was implemented in a computational bronchial tree, built with an iterative algorithm for the generation of bronchial bifurcations and tubes applied inside a virtual 3D pulmonary surface. The computational model was fed and parameterized with computed tomography (CT) experimental data from 5 latently infected minipigs. First, we used CT images to reconstruct the virtual pulmonary surfaces where bronchial trees are built. Then, CT data about TB lesion' size and location to each minipig were used in the parameterization process. The model's outcome provides spatial and size distributions of TB lesions that successfully reproduced experimental data, thus reinforcing the role of the bronchial tree as the spatial structure triggering endogenous reinfection. A sensitivity analysis of the model shows that the final number of lesions is strongly related with the endogenous reinfection frequency and maximum growth rate of the lesions, while their mean diameter mainly depends on the spatial spreading of new lesions and the maximum radius. Finally, the model was used as an in silico experimental platform to explore the transition from latent infection to active disease, identifying two main triggering factors: a high inflammatory response and the combination of a moderate inflammatory response with a small breathing amplitude. |
| Grants: | "la Caixa" Foundation LCF/PR/GN17/50300003 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-500 Agencia Estatal de Investigación PGC2018-095456-B-I00 Instituto de Salud Carlos III CPII18/00031 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Published in: | PLoS computational biology, Vol. 16 (may 2020) , ISSN 1553-7358 |
