Cystic Fibrosis Discovery Provides Insight into Other Pulmonary Conditions

In patients with cystic fibrosis, the mucus molecular bonds become more complex due to inflammation, creating an "elastic sludge" effect, according to a team of researchers from University of California San Francisco who claimed their findings could also be beneficial for other respiratory conditions such as COPD and asthma.

In patients with cystic fibrosis (CF), mucus’ molecular bonds become more complex due to inflammation, creating an “elastic sludge” effect, according to a team of researchers from University of California San Francisco (UCSF) who claimed their findings could also be beneficial for other respiratory conditions such as chronic obstructive pulmonary disease (COPD) and asthma.

An inherited disease, CF makes the mucus in the lungs sticky and difficult to cough up. With no known cure, the 30,000 Americans affected by the condition are especially susceptible to lung infections, a UCSF release pointed out.

For their study published in the Feb. 25 issue of Science Translational Medicine, John Fahy, MD, and his colleagues used a combination of confocal microscopy, confocal imaging, rheology, and biochemical measures of inflammation and oxidation to figure out why CF patients’ mucus becomes elastic.

In doing so, they identified native molecules in the mucus that latch forming long chains, therefore disproving previous research — which implicated increased concentrations of DNA polymers in CF severity.

To verify their findings, researchers exposed mucus samples to two common CF medications, Pulmozyme, a drug that breaks up DNA polymers, and a drug called N-acetylcysteine (NAC) which breaks down polymers’ disulfide bonds located between mucin (which largely makes up mucus) polymers, the release also mentioned.

“We thought Pulmozyme would be more effective than NAC in liquefying the mucus, because CF sputum contains lots of DNA,” the study’s lead author and a professor of medicine at UCSF, John Fahy, MD, said in a news release. “But to our surprise, NAC worked much better.”

Furthermore, by adding oxygen to healthy patients’ sputum samples, the team discovered mucus becomes more elastic through oxidation processes.

Stefan Oscarson, PhD, a medicinal chemist from the University College Dublin (UCD) and the study’s co-contributor, designed TDG — a drug which makes the lungs clear by breaking down disulfide bonds. An experimental drug which has yet to be used on humans, Fahy claimed there is about five years worth of testing before the drug can be deemed viable.