Coughing Unable to Bring Out Mucus in Cystic Fibrosis: Here's Why

Scientists find why it is not easy to clear mucus secretions in the lungs and airways by coughing in a recent experimental study at the University of North Carolina (UNC) School of Medicine and Duke University. The findings of the study appear in the Proceedings of the National Academy of Sciences. Until now, it was not fully clear why coughing is unable to clear the mucus in cystic fibrosis and similar lung conditions. The study team comprising members from a host of scientific disciplines ranging from cell biology to materials science set forth to test the mechanical properties of mucus in airway diseases, such as asthma and cystic fibrosis and whether these could be responsible for difficulties in clearing out the secretions by coughing.

Analyzing Physicochemical Properties of Normal and Disease-Associated Mucus

Typically, the cough reflex creates high-velocity airflow that breaks apart the mucus and simultaneously tears it free from the airway lining which then enables it to be coughed out. This process seems to be affected in lung conditions such as asthma, COPD, cystic fibrosis and chronic bronchitis.

• The team at UNC developed a sophisticated system to test the mechanical force needed to dislodge and break up normal as well as cystic fibrosis (CF) type mucus.
• They obtained airway-lining cells from the lungs of transplant patients and grew them in laboratory dishes. These cells were then able to produce their own mucus and appeared like miniature versions of actual airway lining cells
• Since, mucus is a soft sticky substance, the team developed a method to embed tiny meshes, which bind firmly to the mucus.
• Using a silk thread, this mesh was then connected to a motor having a force sensor to quantify the force required to tear apart the mucus from the lining of the airways
• This arrangement enabled testing of the adhesive and cohesive forces of mucus and comparing these forces in normal mucus and disease associated mucus.

According to Brian Button, PhD, associate professor of biochemistry and biophysics and member of the UNC Cystic Fibrosis Research and Treatment Center 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."

Testing the Efficacy of Popular Cystic Fibrosis Treatments in Altering the Property of Mucus

The UNC and Duke scientists also used this experimental design at the same time, to test the efficacy of two popular forms of CF treatments on the properties mucus in cystic fibrosis.

• First treatment - inhaled saline and hypertonic saline (more salt content than body water) - increases the water content in mucus to make it thinner.
• Other types of treatments or "mucolytic" agents decrease viscoelasticity of mucus by cutting up or separating mucin molecules, thereby reducing the stiffness of the mucus

The study showed that both forms of treatment are equally efficient in reducing the adhesive and cohesive strengths of CF mucus.

Senior author Michael Rubinstein, professor in the Department of Mechanical Engineering and Materials Science at Duke University, said, "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."

For most patients and for minor respiratory ailments, either of these therapies will work, but since their effects are additive, combining the two treatments will be of benefit in patients with severe airway diseases.

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Future Plans

To use the experimental system, it is necessary to study in detail the properties of mucus and response to therapies in other respiratory diseases as well and see how mucus clearance can be improved with newer strategies.

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Reference:

1. Can Scientists Change Mucus to Make It Easier to Clear, Limiting Harm to Lungs? - (http://news.unchealthcare.org/news/2018/november/can-scientists-change-mucus-to-make-it-easier-to-clear-limiting-harm-to-lungs)

Source-Medindia