Mechanisms of mucus transport and bronchial obstruction in COPD – BronchoClogDrain

Bronchial mucus is a hydrogel secreted at the surface of the bronchi to protect them from inhaled contaminants. It is continually transported by the collective beat of cilia that cover the bronchial epithelium, and by cough, a violent air flow capable of dragging mucus plugs away. In COPD, expected to be the fourth cause of mortality by 2030, the mucus transport is altered, causing obstructive crises which impose a hospitalisation in emergency room and worsen the disease. Devices based on the rheology of mucus, developed by the industrials participants of this project, allow to monitor the patients and assist their bronchial drainage. The mechanisms of transport at play are nonetheless poorly understood, limiting by the way the potential of these yet empirical approaches. Our objective is to unveil these mechanisms in order to identify the optimal rheological parameters and assistance actions to follow and manage the mucus transport in patients. We will determine the rheological and biochemical properties of pathological mucus and their role in the different mechanisms of natural and assisted transport, at scales ranging from the epithelium to the whole bronchial tree. We will analyse the mechanisms driving the mobilisation of mucus through its interaction with cilia, and their failing in pathological conditions, as well as the couplings between the different levels of complexity (branching, deformability of the bronchi, mucus hydration) and a global mechanical solicitation. We will integrate this fundamental understanding in a new generation of devices, to favour the early detection (by mucus rheology) and the anticipated treatment (by drainage optimisation) of the crises. Beyond its scientific impact, this interdisciplinary project aims in the long term at providing a medico-economic benefit (reduction of hospitalisations, improvement of the patient prognosis) while stimulating the development of the involved industrial partners.