MucoReaDy: Mucus, cystic fibrosys
and respiratory dysfunction

Cystic fibrosis is a progressive, multisystem, genetic disease that is associated with substantial morbidity and early mortality. Infants with cystic fibrosis typically present characteristic disease manifestations, including lung disease, elevated sweat chloride concentrations, respiratory symptoms, meconium ileus, failure to thrive, exocrine pancreatic insufficiency, and absent vas deferens (cf. figure 1). Small airway dysfunction detected by lung clearance index (LCI) and bronchiectasis is evident in young infants with cystic fibrosis. Pulmonary dysfunction progressively worsens over time, leading to a decline in percent predicted forced expiratory volume in 1s (ppFEV1), heralding advanced lung disease that is often irreversible. Newborn screening has enabled early initiation of standard-of-care therapies in children with cystic fibrosis, leading to improvements in measures of growth, nutrition, and lung disease. Yet premature mortality remains, with a median predicted survival of 47 years. Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to reduce the quantity or/and the function of the CFTR protein on cell surfaces.

The objective of this project is to study the alteration of the mechanism of mucocilicary clearance for the pathology of cystic fibrosis (CF) and/or aspergillosis (Allergic Broncho-Pulmonary Aspergillosis or ABPA), in a mucus dynamics perspective. Hence getting an accurate understanding of the mechanisms involved in the mucus production, maturation, self-stratification and above all its motion induced by its interactions with its complex and mobile surrounding is essential.

The clinical application of this project is to provide a simple and inexpensive diagnostic that will show if the patient gets a better mucociliary clearance, even if not yet significant on spirometric values. The result must be able to check (at least helping to get an idea) the efficiency of a drug therapy (for CFTR modulators like the lumacaftor and ivacaftor combination therapy), or evaluate the risks of microbial resistance to the drug therapy (for Aspergillosis or Pseudomonas aeruginosa infection).