Key Point:

The CF airway appears to contain decreased amounts of mucus rather than increased amounts as was previously believed.

WINSTON-SALEM—It has long been assumed that patients with cystic fibrosis (CF) hypersecrete airway mucus but a recent study suggests that the opposite is true. In the study, sputum from 12 patients with CF displayed mean decreases in the major gel-forming mucins MUC5AC and MUC5B of 93% and 70%, respectively, compared to sputum from 11 healthy controls without airway obstruction.¹

“Our study shows how common knowledge is commonly wrong,” remarked Bruce K. Rubin, MD, one of the study authors, in an interview with Pulmonary Reviews. “We are excited that the study may fundamentally change the way we look at CF,” added Dr. Rubin, Vice Chair of the Department of Pediatrics at the Wake Forest University School of Medicine in Winston-Salem.

The study in no way suggests, of course, that airway obstruction is unimportant in CF. “There is clearly a lot of foul stuff in the CF airway that needs to go away,” said Dr. Rubin. “But it is better described as pus composed of neutrophils and neutrophil breakdown products such as DNA.”

The authors drew that conclusion when they compared sputum from CF patients to that of sputum from patients with bronchitis. Much greater levels of mucin were seen in the bronchitis sputum whereas the CF sputum contained much larger amounts of DNA.

The results of the study were unchanged when the authors subsequently enrolled an additional 23 patients with CF. Their findings are presumably disappointing to drug companies that have been attempting to create medications that reduce mucus secretion in the CF airway.

“These companies may not be developing products that will be of great benefit to patients with CF,” Dr. Rubin speculated. A better course of action, he suggested, would be to better understand the mechanism behind abnormal mucus secretion in CF before trying to develop medications that alter mucus secretion in patients with the disease.

“We must first determine if mucin-producing cells in CF patients are not secreting enough mucin, if they turn over before they produce adequate mucin, or if there is some other reason why airway mucin is decreased in CF,” Dr. Rubin advised. “Then we could find out if the problem is correctable with an agent that increases mucin, increases the secretion of the mucin that is already formed, or prevents the turnover of mucin-producing cells before they are mature and able to produce mucin.”

—Timothy Begany

Reference
1. Henke MO, Renner A, Huber RM, et al. MUC5AC and MUC5B mucins are decreased in cystic fibrosis airway secretions. Am J Respir Cell Mol Biol. 2004;31:86-91.