CF and pH – Lung Acidity in Cystic Fibrosis Increases Infection

08 July 2012
Posted by Ben Valsler.

Sufferers of Cystic Fibrosis, or CF, have lower pH in their airways and this impairs their ability to kill bacteria, leading to increased infections, inflammation and ultimately damage to lung tissue.

CF is a genetic condition caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator, or CFTR, gene.  The CFTR protein regulates the movement of ions across membranes, including the lining of the lungs, and its failure leads to symptoms such as the build up of thick, viscous mucus.  People with CF are especially vulnerable to lung infections, and these infections are ultimately the main cause of illness and death in CF patients, but until now it's not been clear how CF impaired the ability of the immune system to tackle infection.

An example of a breathing treatment for a younger Cystic fibrosis patient.Writing in Nature, Joseph Zabner and colleagues at the University of Iowa immobilised Staphylococcus aureus bacteria on solid grids and placed these on the lung surface of both healthy and CF pigs.  Even a brief exposure to healthy lung tissue killed the bacteria, while only half as many were killed in the CF lungs.  This pattern held up in vitro and against other bacteria; consistently, Airway Surface Liquid, or ASL, from CF pigs killed fewer bacteria than from their healthy littermates.

This showed that ASL itself rapidly kills bacteria, and that this effect was impaired in CF.  There were no obvious differences in the abundance of antimicrobial proteins between CF and non-CF, so the researchers concluded it must have been another chemical factor.  As the CFTR protein is linked with secretion of hydrogen carbonate, or HCO3-, an ion important in pH buffering, they decided to investigate the effect of pH.  They found that both in vivo and in vitro, CF lung fluids showed a lower pH.  Raising the pH of CF lung fluids restored the ability to kill bacteria.

This simple, elegant study suggests that correcting lung fluid pH could prevent infection taking hold in CF lungs, and could be achieved by something as simple as a bicarbonate aerosol.

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