rapid-viscoelastic-characterization-airway-mucus-using-benchtop

Rapid Viscoelastic Characterization of Airway Mucus Using a Benchtop Rheometer

In muco-obstructive lung diseases (e.g., asthma, chronic obstructive pulmonary disease, cystic fibrosis) and other respiratory conditions (e.g., ...

The University of North Carolina at Chapel Hill

Cystic fibrosis (CF) is a recessive genetic disease that is characterised by airway mucus plugging and reduced mucus clearance. There are currently alternative hypotheses that attempt to describe the abnormally viscous and elastic mucus that is a hallmark of CF airways disease, including: 1) loss of CF transmembrane regulator (CFTR)-dependent airway surface volume (water) secretion, producing mucus hyperconcentration-dependent increased viscosity, and 2) impaired bicarbonate secretion by CFTR, producing acidification of airway surfaces and increased mucus viscosity.A series of experiments was conducted to determine the contributions of mucus concentration  pH to the rheological properties of airway mucus across length scales from the nanoscopic to macroscopic.For length scales greater than the nanoscopic,  those relevant to mucociliary clearance, the effect of mucus concentration dominated over the effect of airway acidification.Mucus hydration and chemical reduction of disulfide bonds that connect mucin monomers are more promising therapeutic approaches than alkalisation.

Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH.

Cystic fibrosis (CF) is characterised by the accumulation of viscous adherent mucus in the lungs. While several hypotheses invoke a direct relationship with cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction ( acidic airway surface liquid (ASL) pH, low bicarbonate (HCO ) concentration, airway dehydration), the dominant biochemical alteration of CF mucus remains unknown.

Treatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties  hydration.

Mucus hyperconcentration in cystic fibrosis (CF) lung disease is marked by increases in both mucin and DNA concentration. Additionally, it has been shown that half of the mucins present in bronchial alveolar lavage fluid (BALF) from preschool-aged CF patients are present in as non-swellable mucus flakes. This motivates us to examine the utility of mucus flakes, as well as mucin and DNA concentrations in BALF as markers of infection and inflammation in CF airway disease.

Article	Year
Pathological mucus and impaired mucus clearance in cystic fibrosis patients result from increased concentration, not altered pH. The European respiratory journal\| PubMed ID: 30361244	2018
Treatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties hydration. The European respiratory journal\| PubMed ID: 34172469	2022
Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society\| PubMed ID: 35437233	2022

Matthew R. Markovetz

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