Multiscale simulation of the respiratory epithelium: towards the development of a numerical tool to model human lungs

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Chronic respiratory diseases such as asthma or chronic obstructive pulmonary disease are a major health problem affecting almost 1 billion people, a number that continues to grow due to the increased pollution in urban societies. At the root of these respiratory problems is a transport phenomenon that takes place in the lungs, named the "mucociliary clearance" (MCC), with a fascinating physics involving mass exchanges through the epithelium, the coordinated beating of microscopic flexible cilia embedded in a two-fluid environment and the time-dependent respiratory air flow in deformable conduits. The long-term objective of this present program is to develop new numerical tools able to investigate the flow dynamics in human lungs. Compared to heart, these are an even more challenging organ for numerical methods mainly because of their multiscale nature (from few microns for the cilia length to centimeters for the trachea's diameter) and complex geometry (23 generations of dichotomous branching). Through my former Discovery grant, a first solver based on the coupled lattice Boltzmann / immersed boundary method has been developed. The beating of cilia carpets has been simulated in a two-phase fluid medium with different properties. The results showed that a coordinated motion of cilia (metachrony) may emerge due to a simple hydrodynamic retroaction. Metachronal waves moving in the opposite direction compared to the main flow were found to better transport bronchial mucus with less energy consumption. Numerical developments are however still required to simulate more representative conditions at the epithelium surface then for the whole respiratory tract. It includes the modelling of the non-Newtonian behavior of bronchial mucus, the mass exchanges at the epithelium surface (porous medium), the three-dimensional cilia beating pattern, the elastic nature of the bronchial tree during breathing and the superimposed air flow. The new insights gained at the microscopic scale will serve to develop a macroscale model able to simulate several generations in the upper part of the bronchial tree. These micro- and macroscale models will be systematically compared to experimental data from new experimental facilities developed at Université de Sherbrooke. Eight highly qualified personnel will be trained during this program and evolved in a very stimulating environment, interacting with engineers, biologists and clinicians. In Canada, asthma is the third most common chronical disease with 3 millions of patients, inducing around $1.6 billion costs to the country. A better understanding of MCC from a mechanical point of view may serve to better manage such diseases. It will also pave the road to other applications where the coordinated motion of cilia or flagella is involved: the fluid propulsion of marine animals, the pumping and mixing in microfluidic devices and the fluid transport in other human organs (brain, Fallopian tubes, eyes).