Increased Acidity Linked to Production of Thick, Sticky Mucus in Cystic Fibrosis

Increased Acidity Linked to Production of Thick, Sticky Mucus in Cystic Fibrosis

A research team at the University of Iowa’s Pappajohn Biomedical Institute (PBI) conducted a study on mucus abnormalities in animal models of cystic fibrosis (CF), and found that increased acidity was the major contributor to the elevated viscosity in CF airway surface liquid, a trait that makes the lungs of CF patients more vulnerable to persistent bacterial infections.

The research paper, “Acidic pH increases airway surface liquid viscosity in cystic fibrosis,” was published in The Journal of Clinical Investigation.

Cystic fibrosis is a genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is responsible for secreting bicarbonate ions into the airway surface liquid. The normal flow of bicarbonate is essential to the maintenance of the equilibrium of airway acidity, as the loss of bicarbonate flow has been shown to alter mucus properties.

Previous research from the lab of Michael Welsh, a professor of internal medicine and director at PBI, showed that the loss of CFTR results in increased acidity of the liquid lining the lungs’ airways, in both human patients and pigs with cystic fibrosis. However, it remains unknown whether it is the increased acidity or concentration of bicarbonate ions that results in the increased viscosity of the airway liquid.

By studying airway surface liquid (ASL) collected from newborn cystic fibrosis piglets and ASL on cultured airway epithelia, researchers were able to differentiate the effects of increased acidity and concentration of bicarbonate on the physical properties of ASL. The results suggested that increased acidity is responsible for the viscosity by changing the way mucin molecules (the major protein component of mucus) interact.

The findings explain why a current successful therapy, using hypertonic saline, may induce its beneficial effect — by altering electrostatic interactions in mucus. Furthermore, the scientists reported that the overly viscous mucus present in cystic fibrosis is likely to be present at birth rather than developing over time.

“The results of our study suggest that decreasing acidity, reducing calcium concentration, and/or altering electrostatic interactions (of mucus proteins) in airway surface liquid could decrease mucus viscosity and, therefore, might benefit patients in the early stages of CF,” said the study’s lead author, Dr. Xiao Xiao (Sammi) Tang in a news release.

Researchers believe the findings can also be relevant for other lung diseases in which airway surface liquid is unusually acidic, such as chronic obstructive pulmonary disease (COPD), asthma, and acute respiratory distress syndrome.

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