For the first time, scientists at the UNC School of Medicine and Duke University demonstrated why coughing often cannot tear mucus apart and away from the airway lining. They also showed how to make mucus thinner and less sticky so coughing can become a therapeutic aid. The discovery helps explain how cystic fibrosis harms lungs over time and underscores the importance of therapies that alter mucus enough to give immediate relief to people with CF.
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In healthy people, mucus is 98% water. Less than 1% of ordinary mucus consists of long, sticky, chain-like proteins called mucins, which give mucus its gel-like properties. CF, chronic bronchitis, and other “muco-obstructive” diseases feature mucus dramatically more viscous and elastic than normal, almost gelatin-like because it is loaded with mucins. In CF mucus, for example, the amount of mucins jumps to 10% and the amount of water decreases to 79%.
Researchers at UNC developed a sophisticated system for testing the mechanical forces required to dislodge and fracture normal and CF-type mucus. The scientists first took airway-lining cells from the lungs of transplant patients and cultured them in laboratory dishes. These cells produced their own mucus layer. “We measured the adhesive forces that bind mucus to the airway lining and the cohesive forces that hold mucus together, and identified several agents that show promise in reducing the strength of mucus’s adhesive and cohesive interactions,” said Senior author Michael Rubinstein, professor in the Department of Mechanical Engineering and Materials Science at Duke University.
“The tools developed in this study will help us test strategies to improve mucus clearance in several important diseases where clearance fails,” said lead author Brian Button, PhD, associate professor of biochemistry and biophysics at UNC-Chapel Hill. “We found that the adhesive and cohesive strengths of mucus increase dramatically when the ratio of mucins to water is higher than normal. In CF mucus, those strengths exceeded the forces produced by coughing. That means coughing would have a substantially reduced ability to clear mucus.”