Rheology of pulmonary mucus

Objectives

Obstructive lung diseases (cystic fibrosis, COPD, primary ciliary dyskinesia, etc.) are a major cause of mortality worldwide. They share the common feature that pulmonary mucus, which protects the bronchial epithelium, flows less easily than in healthy individuals and tends to form plugs that obstruct the airways. It has been shown that the rheological properties (viscoelastic moduli, yield stress, etc.) of mucus are significantly higher in these conditions. Based on this, we initiated a collaboration in 2018 with the company Rheonova, which commercializes a rheometer specifically designed for hospital use, with the idea that rheological characterization of sputum could provide diagnostic insights and potentially serve as a biomarker for patient monitoring. Interpreting these rheological measurements and linking them to sample composition and patient clinical status remains a major question, for which current biological and medical knowledge is still limited.

Results

We have conducted a series of projects (LabCom ANR Mucus, Plan de relance Mucus 2, Région Project Mucus 3, and ANR Bronchocloggdrain) in collaboration with Rheonova and the CHU Grenoble-Alpes (Max Maurin, bacteriologist; Bruno Degano, pulmonologist) to better understand pulmonary mucus rheology using various approaches.
We work with sputum collected during physiotherapy sessions at the hospital, mucus samples obtained in vivo during endoscopies, as well as model samples derived from snail mucus. Standard rheometry is performed on sputum samples, and passive microrheology using our fast confocal microscope is employed. This latter technique allows working with very small volumes (as in in vivo samples) and quantifies local heterogeneities at small scales.
This research topic, initiated a few years ago in the laboratory, required significant effort to establish protocols, which are now systematically implemented in the ongoing PhD projects of K. Shaalan and A. Raffournier.

References

Esteban Enjuto, L., Robert de Saint Vincent, M., Maurin, M., Degano, B., & Bodiguel, H. (2023). Sputum handling for rheology. Scientific Reports, 13(1), 7695.

Milian, D., Robert de Saint Vincent, M., Patarin, J., & Bodiguel, H. (2023). Gastropod slime-based gel as an adjustable synthetic model for human airway mucus. Biomacromolecules, 25(1), 400-412.