New Test of Mucus Properties May Help with Coughing and Airway Clearance in CF
A new test was able to assess various properties of the mucus that accumulates in the lungs of people with cystic fibrosis and other pulmonary diseases, and may help to find treatments — or a combination of treatments — for CF patients that can make coughing a more viable way of clearing mucus from their airways.
Developed by researchers at University of North Carolina at Chapel Hill, the assay was described in the study “Roles of mucus adhesion and cohesion in cough clearance,” published in the Proceedings of the National Academy of Sciences.
Pulmonary mucus clearance is a critical mechanism in protecting the body from potentially harmful microorganisms and particulates — mucus works to trap pathogens. But in illnesses like cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma, this clearance system is faulty, and the resulting accumulation of thick mucus inside the lungs that promote infection and impair the respiratory function.
Efficient mucus clearance depends on the normal activity of the cells lining the airways, but also on the water and ion content of the mucus, and on the right balance of adherent molecules called mucins.
To better understand the mechanism of mucus clearance induced by cough, researchers developed a peel test assay that mimics several features of airway lining cells, using tissue from both healthy individuals and CF patients.
They collected airway-lining cells from the lungs of transplant patients, and cultured them in the laboratory. Then, small meshes were embedded in cell cultures to firmly bind them to the mucus. Meshes were connected to a motor with a force sensor, to quantify the force needed to pull and tear the mucus.
Using this technique, researchers could study the adhesive and cohesive forces of mucus, and explore ways of facilitating mucus clearance.
“The tools developed in this study will help us test strategies to improve mucus clearance in several important diseases where clearance fails,” Brian Button, PhD, and associate professor at UNC and the study’s lead author, said in a university press release.
Airflow-mediated mucus clearance through cough works via either cohesive failure, which involves the breakdown of the mucus layer through the tearing of mucin strands (mucins are proteins that give mucus its gel-like properties), or adhesive failure, which requires the breakdown of mucus-cell bonds.
Experiments showed that in CF patients — known to have mucus about 20% more concentrated in organic matter than healthy individuals — the strength and peeling velocity of mucus is much higher. This finding helps to explain why CF patients often cannot expel lung mucus simply by coughing.
“We found that the adhesive and cohesive strengths of mucus increase dramatically when the ratio of mucins to water is higher than normal,” said Button, who is also a member of the UNC Cystic Fibrosis Research and Treatment Center at UNC-Chapel Hill. “In CF mucus, those strengths exceeded the forces produced by coughing.”
But when looking at airway cell-mucus interaction, the researchers saw no difference in adhesive strength between CF and non-CF samples compared at the same mucus concentration.
Analysis of the cohesive strength of sputum collected from CF and COPD patients with varying disease severity showed that a higher cohesive strength was strongly correlated with mucus concentration, but is not dependent on disease type.
Next, using their peel test assay, the team tested treatment approaches that included hydrating agents (like inhaled saline and hypertonic saline solutions) and more classic mucolytic agents (mucus-thinning medications).
Saline solution to hydrate mucus was found to significantly reduce the adhesive and cohesive strengths of CF mucus, as it also reduced its concentration by half. Acetylcysteine, a mucolytic agent that can prevent normal mucin strands formation and binding, was also found to effectively reduce the adhesive/cohesive strengths of CF mucus, allowing for an easier clearance.
These results suggested that the use of hydrating and mucolytic agents, or both combined, in CF patients could aid mucus clearance through coughing.
“Restoration of cough efficacy may be most effectively provided by restoring mucus concentrations to normal ranges with hydrating agents coupled with viscosity-lowering agents,” the researchers wrote.
“Our research suggests that this approach could allow coughing to become beneficial to these patients, just as it is for the rest of us when we battle less serious ailments,” Button said.
The team plans to use their experimental peel test system to study the properties of mucus and the effects of therapies in other lung diseases.