More Mucus May Protect Cystic Fibrosis Patients
Reversing conventional wisdom, doctors reported Thursday that the pus and infection filling the airways of cystic fibrosis patients may stem from too little lung mucus -- not too much, as physicians always assumed.
Doctors at Wake Forest University examined the phlegm in the airways of 12 patients with the disease and found very little mucus -- as little as 7% of the mucus proteins that usually coat the lungs and help shield them from bacteria.
These contrary results require a reevaluation of current treatments for cystic fibrosis and may lead to more effective therapies based, ironically, on adding mucus as a barrier to lung infection.
“We were absolutely stunned by these results,” said Dr. Bruce K. Rubin, an author of the study in the current issue of the American Journal of Respiratory Cell and Molecular Biology. “All the stuff these people were coughing up was not mucus.”
Cystic fibrosis, which affects about 40,000 children and adults in the U.S., develops when children inherit two copies of a defective gene from their parents. The disease is characterized by frequent chest infections, persistent coughing and breathing difficulties. Patients have a median lifespan of about 30 years.
Dr. Markus Henke, lead author of the study, set out to quantify the amount of mucus produced by patients with the disease. He and Rubin measured levels of proteins, called mucins, in 12 patients with cystic fibrosis and 11 without lung disease.
Examining two mucins that compose lung mucus, they found that the cystic fibrosis patients had a 70% reduction in one protein and a 93% reduction in the other.
The substance clogging the lungs turned out to be pus -- broken down white blood cells and bacteria, Rubin said.
The lack of mucus may explain why the disease causes so many lung infections. “Mucus is a great barrier to infection,” Rubin said. But, “because it doesn’t get into the airway, bacteria are free to go wild in the lungs.”
Most cystic fibrosis treatments rely on reducing infection with antibiotics and loosening or breaking down the fluid that is already in the airway.
Rubin now wants to develop alternative therapies targeting mucus production. He suspects that epithelial cells lining the lungs are making the mucus, but somehow it is not emerging from the cells.
Normally, the cells produce mucin proteins and, in a process called exocytosis, push them through the outer membrane into the airway.
But in cystic fibrosis, “the cells are getting stuffed fat with this mucus that’s not getting out,” he said, “and at the same time, the airway is being deprived of something that’s important.”
