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Updated: Sep 28, 2025

Rapid Viscoelastic Characterization of Airway Mucus Using a Benchtop Rheometer
Published on: April 21, 2022
Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in
Takafumi Kato1,2, Giorgia Radicioni1, Micah J Papanikolas3
1Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Abstract:
Cystic fibrosis (CF) is characterized by abnormal transepithelial ion transport. However, a description of CF lung disease pathophysiology unifying superficial epithelial and submucosal gland (SMG) dysfunctions has remained elusive. We hypothesized that biophysical abnormalities associated with CF mucus hyperconcentration provide a unifying mechanism. Studies of the anion secretion-inhibited pig airway model of CF revealed elevated SMG mucus concentrations, osmotic pressures, and SMG mucus accumulation. Human airway studies revealed hyperconcentrated CF SMG mucus with raised osmotic pressures and cohesive forces predicted to limit SMG mucus secretion/release. Using proline-rich protein 4 (PRR4) as a biomarker of SMG secretion, CF sputum proteomics analyses revealed markedly lower PRR4 levels compared to healthy and bronchiectasis controls, consistent with a failure of CF SMGs to secrete mucus onto airway surfaces. Raised mucus osmotic/cohesive forces, reflecting mucus hyperconcentration, provide a unifying mechanism that describes disease-initiating mucus accumulation on airway surfaces and in SMGs of the CF lung.
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