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Proc Natl Acad Sci U S A. 2018 Dec 4;115(49):12501-12506. doi: 10.1073/pnas.1811787115. Epub 2018 Nov 12.

Roles of mucus adhesion and cohesion in cough clearance.

Author information

1
Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248.
2
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7260.
3
Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7575.
4
Department of Materials Science and Engineering, University of Virginia, Charlottesville, VA 22904.
5
Department of Chemical Engineering, University of Virginia, Charlottesville, VA 22904.
6
Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248; michael.rubinstein@duke.edu.
7
Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708.
8
Department of Biomedical Engineering, Duke University, Durham, NC 27708.
9
Department of Physics, Duke University, Durham, NC 27708.
10
Department of Chemistry, Duke University, Durham, NC 27708.

Abstract

Clearance of intrapulmonary mucus by the high-velocity airflow generated by cough is the major rescue clearance mechanism in subjects with mucoobstructive diseases and failed cilial-dependent mucus clearance, e.g., subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Previous studies have investigated the mechanical forces generated at airway surfaces by cough but have not considered the effects of mucus biophysical properties on cough efficacy. Theoretically, mucus can be cleared by cough from the lung by an adhesive failure, i.e., breaking mucus-cell surface adhesive bonds and/or by cohesive failure, i.e., directly fracturing mucus. Utilizing peel-testing technologies, mucus-epithelial surface adhesive and mucus cohesive strengths were measured. Because both mucus concentration and pH have been reported to alter mucus biophysical properties in disease, the effects of mucus concentration and pH on adhesion and cohesion were compared. Both adhesive and cohesive strengths depended on mucus concentration, but neither on physiologically relevant changes in pH nor bicarbonate concentration. Mucus from bronchial epithelial cultures and patient sputum samples exhibited similar adhesive and cohesive properties. Notably, the magnitudes of both adhesive and cohesive strength exhibited similar velocity and concentration dependencies, suggesting that viscous dissipation of energy within mucus during cough determines the efficiency of cough clearance of diseased, hyperconcentrated, mucus. Calculations of airflow-induced shear forces on airway mucus related to mucus concentration predicted substantially reduced cough clearance in small versus large airways. Studies designed to improve cough clearance in subjects with mucoobstructive diseases identified reductions of mucus concentration and viscous dissipation as key therapeutic strategies.

KEYWORDS:

airway physiology; cough; cystic fibrosis; lung disease; mucus clearance

PMID:
30420506
PMCID:
PMC6298066
DOI:
10.1073/pnas.1811787115
[Indexed for MEDLINE]
Free PMC Article

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