Biophysical differences between COPD, CF and healthy airways mucus.

Abstract: An improved understanding of the mucus biophysical alteration in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) patients is a milestone towards a more accurate and effective treatment of these common and highly debilitating conditions. Little is known about the variations in mucus structure between ill and healthy individuals. An established fact, however, is the role of the mucus obstruction in the exacerbation of the two conditions which impairs the physiological cleaning mechanism of the airways (mucociliary clearance) and is assessed as the strongest predictor of mortality. Therefore, it appears relevant to investigate which properties and structural changes are responsible of the impaired clearance of airway mucus. This thesis presents investigations of mucus on the basis of mucin structure observed in healthy, COPD and cystic fibrosis bronchial mucus samples. AFM (atomic force microscopy) and synchrotron SAXS (small angle X-ray scattering) techniques were used to characterise the structural features of the mucin molecules and allowed to identify the dumbbell structure of airways mucin monomers. The analysis of structural and dimensional features of mucins, highlighted a greater similarity of COPD with the healthy sample rather than with cystic fibrosis. The water sorption analysis using QCM-D (quartz crystal microbalance with dissipation monitoring), established a divergent behaviour between COPD and cystic fibrosis. Compared to healthy specimen, the mucus from COPD donors, showed a greater tendency to absorb water while cystic fibrosis mucus, in contrast, displayed the lowest water absorption.