Mucosal rheology in the airways of patients with severe lung disease. A bibliographic, experimental and computational insight.

Worldwide rising pollution, global warming and demographic explosion over the last decades increase the rate of severe acute (correlated to SARS-Cov-2) and chronical (Asthma, Chronical Obstructive Bronch Pneumopathy (COPB) and cystic fibrosis (CF)) respiratory pathologies. These are associated with a clearance defect that causes congestion basically linked to a change in the production, composition and rheology of bronchial mucus. It trade to the necessity to carry out rheological studies to characterize the behaviour of this viscoelastic shier-thinning fluid. In this context the project undertaken by the experimental and computational research laboratories of the Aix-Marseille University (M2P2 and ISM2) and the C2VN (Cardio-Vascular and Nutrition Research Centre of La Timone University Hospital in Marseille) is about the intensification of research in this field with a dual aim. First able determine the rheological properties of airway mucus overcoming the problems of small quantity and significant variability (in composition and behaviour) of natural samples. At second provide a fluid-dynamic model for the flow of mucus in lungs, based on a relevant rheological parameter or model. It will grant a technical improvements of the air-respiratory machines, and an increase of the efficiency of the therapeutic procedure as a function of the possible pathology. To pursue both purposes this thesis project produced a preliminary intensive literature review that allows to characterizing the change in pulmonary mucus composition and rheological behaviour for for COPD, asthma and CF pathologies. Even bibliographic studies provided standard operating modes and components to reconstruct pulmonary mucus at laboratory scale. For each constituent element has been identified their interactional and rheological function and a corresponding component in the real pulmonary mucosa. The literature research has been integrated by the analysis of in Vitro real Bronchial Mucus (harvested from C2VN's epithelia cellular cultures coming from sane and sick patients) and in Vivo real Nasal Mucus (coming from medical consultations of Asthmatic patients in Marseilles Public Assistance Hospital). With the composition and rheological ranges gained in the preliminary steps has been defined and performed a lung mucosa reconstruction procedure, minimizing the number of experiments to carry out with experimental matrixes. The variation in composition of pulmonary reconstructed mucus allowed to verify and quantify the connection between the rheological behaviour changes and the main components (Mucins, DNA, Lipid and Bacteria shield linkers) interactions. The experimentation required the planning of an interactional design of experiments. For that and the interaction evaluations the AZURAD software was used. Rheological analyses were conducted with an Anton Paar MCR 302 rheometer, coupled with the Rheocompass software. The mucosa rheological behaviour was interpreted with the Herschel-Buckley model. A MATLAB programme was implemented to identify and optimize, with an excel spreadsheet, the parameters of the model. The collected data were compared with a fluid-dynamic model developed by another team of the M2P2 laboratory. This led to further validation of this model and highlighted how the two projects amplify their effectiveness (providing a biochemical, rheological and fluid-dynamic view) in the field of combating respiratory diseases.