New Test of Mucus Properties May Help with Coughing and Airway Clearance in CF
There are several recent treatment options available to help treat and prevent chest infections, as well as to thin out mucus clogging up the lungs.
In the United States, there are currently 30,000 individuals living with cystic fibrosis - a progressive, hereditary condition that results in persistent lung infections and airway obstruction, making it difficult to breathe. There is no cure for cystic fibrosis, although there are several treatment options available to help treat and prevent chest infections, as well as to thin out the mucus clogging up the lungs.
Now, a new test has been introduced, one which is designed to assess a variety of different properties of the mucus that builds up in the lungs of individuals with cystic fibrosis and other pulmonary diseases. Developed by a team of researchers at the University of North Carolina School of Medicine and Duke University, the test may able to help target the most effective treatment or combination of treatments for these individuals.
The findings of the study were published in the Proceedings of the National Academy of Sciences.
A more practical approach to altering mucus
For individuals in good health, mucus is an ally. It targets potential pathogens so that no harm can come to the lungs. However, for individuals with pulmonary diseases like cystic fibrosis, mucus becomes thick and sticky because of problems with the cystic fibrosis transmembrane conductance regulator protein. Normally, the protein (which runs in families) is responsible for transporting chloride to the cell membranes of several regions in the body. But when the protein is faulty, chloride becomes imprisoned in the cells. It is unable to hydrate cell surface, resulting in the mucus becoming dehydrated and building up in the lungs to the extent of triggering infections, chronic disease, and early death.
On that note, the team of researchers aimed to prove why coughing alone cannot get rid of mucus, as well as to show how mucus can be thinned out to the point of making coughing a therapeutic aid and providing immediate relief. They developed a test that imitates the properties of mucus in individuals in good health, as well as in those with cystic fibrosis. Upon examining the airway-lining cell samples in the laboratory, they blended them together with small meshes connected to a force sensor motor.
Using this method, the researchers were able to identify the forces necessary to jiggle and thin out the mucus. They found that facilitation of mucus clearance depends on the regular activity of the airway-lining cells. They also found that the process depends on the water and ion content of the mucus and on the proper balance of mucins. “The tools developed in this study will help us test strategies to improve mucus clearance in several important diseases where clearance fails” said Brian Button, lead author of the study and associate professor at UNC.
Opening novel therapeutic windows
Button and his team of researchers identified two different types of mucus clearance by means of coughing:
- Cohesive failure – involving the direct collapse of the mucus layer;
- Adhesive failure – involving the collapse of mucus-cell bonds;
They found that in the group of individuals in good health, mucus in 98% water. Controversy, in the group of individuals with cystic fibrosis, the mucus was found to be at 79%, meaning it was more concentrated by 20%. This finding led the researchers to better understand why individuals with cystic fibrosis often cannot get rid of mucus from their lungs simply by means of coughing. “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” said Button. However, when observing the airway and mucus interaction, they noticed that the two groups exhibited similar cohesive and adhesive properties.
The research team also used their newly designed test to determine the effectiveness of two common types of CF therapies:
- Mucus thinners, which increases the content of water in the mucus to make it thinner;
- Mucolytic therapies, which break up the mucin molecules to make the mucus more elastic;
They found that both types of CF therapies work well when it comes to aiding easier clearance through coughing. “For patients, one of these types of therapy should help. But their effects are additive, so it would probably be better to combine both. And 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, such as viruses” said Button.
The researchers derived to the conclusion that the most effective approach to restoring cough efficacy may be to bring back mucus concentration to normal levels. This can be done by combining hydrating agents with viscosity-reducing agents.
Now, they plan to use their newly developed test to examine the mechanical properties of mucus and the effects of various therapies on other pulmonary diseases.
Coming down the pipeline
By now, it is well known that airway mucus obstruction plays a vital role in the onset of cystic fibrosis. Therefore, in order to advance the developments of new treatments for this disease, researchers are continuously studying the secretion of mucus. They remain focused on answering the following questions:
- Where is mucus most important?
- Why is there an abnormal amount of mucus in cystic fibrosis?
- Why is CF mucus more susceptible to infection?
- How does mucus affect the lungs?
- How do the properties of mucus affect its structure?
Researchers are also studying how much liquid covers the airway-lining cells and what factors give rise to airway hydration. Additionally, they are analyzing the role of calcium-activated chloride channels in the hydration of mucus, as well as whether these channels can somehow be stimulated to boost the flow of fluids within the lungs.
In recent years, studies have been able to deliver a broader and more accurate image of the progression of a hereditary condition, like cystic fibrosis. Nevertheless, a better understanding of how mucus is secreted normally is necessary in order to better understand the mechanisms underlying airway mucus obstruction. When this occurs, restoring its proper consistency, function, and germ-fighting capabilities in individuals with cystic fibrosis will hopefully be a viable option one day.