A team led by UC San Francisco professor of medicine John Fahy, MD, has discovered why mucus in the lungs of people with cystic fibrosis (CF) is thick, sticky and difficult to cough up, leaving these patients more vulnerable to lung infection.
They found that inflammation causes new molecular bonds to form within mucus which transforms it from a liquid to a sludge.
This research has implications for other lung conditions characterized by thickened mucus, such as chronic obstructive pulmonary disorder (COPD) and asthma.
The scientists also made headway in the lab in exploring a potential new therapeutic approach to dissolve those bonds and return the mucus to a liquid that is easier for the lungs to clear.
Polymers – naturally-occurring molecules in mucus that form long chains – are the key to the discovery. Originally it was thought that there was just an increased concentration of these polymers with CF sufferers but now they know that more bonds form they just need to develop a drug that will break down and dissolve these extra bonds safely.
Fahy likened the polymers to logs floating down a river. “The logs can float down the river as long as they are floating independently,” he said. “But if you bolt them together side to side, they will clog the river.”
The researchers found that inflammation causes the extra disulphide bonds to form, when mucin polymers are exposed to highly reactive oxygen molecules released by inflammatory cells in a process called oxidative stress. Patients who are treated with pure oxygen have long been known to develop sticky mucus and this could be an unfavourable side-effect of the oxygen that’s used to treat them.
A new drug called TDG has been developed to target these mucin polymer bonds to re-liquefy a patient’s mucus but it is still going through the testing stages at present and will be at least 5 years away.
This new finding that explains the reason behind mucus thickening will not only help CF sufferers but other patients with lung diseases such as COPD and asthma. This potential new treatment in the pipeline could help millions of patients enjoy an easier more comfortable life if this drug can eliminate the problems of thickened mucus. It not only clogs up the lungs and makes breathing difficult and coughing it up distressing but also increases the risk of harmful infections taking hold, which could also be reduced with this new treatment.

References: www.ucsf.edu