Decreasing Acidity of Airway Liquid in Newborn CF Patients May Reduce Infection Risk, Study Suggests

Normalizing the acidity in the thin layer of liquid covering the airways of newborns with cystic fibrosis might make them more resistant to bacterial infections, a study has found.

The study’s researchers also identified two proteins, pendrin and ATP12A, that could be targeted to regulate acidity levels of the airway liquid in these infants, which is “significantly” more acidic in CF patients than in healthy people based on the pH scale.

The study, “Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis,” was published recently in the journal Nature Scientific Reports.

Airway secretions show evidence of  Staphylococcus aureus (S. aureus) infection in children born with CF within the first hours of life. But how this susceptibility comes about is not well-understood.

“There is no clear understanding of the initial host response, when S. aureus bacteria infiltrate the pristine surface of the newborn airway, with prolonged time of contact and continuous reseeding from infected mucus plugs,” the study said. “It is therefore crucial to clarify the pathogenesis of these very early steps to counteract the pro-infectious vicious circle.”

A previous study suggested that the airway liquid of CF patients is highly acidic, and this imbalance could affect defense mechanisms against bacteria.

Researchers in France created a lab model that replicated the airways of newborns, and measured the differences in acidity between cells extracted from healthy people and those from CF patients to evaluate its role in bacterial infection.

This work confirmed higher-than-normal acidity in the airway surface liquid of CF patients.

Airway acidity is normally regulated by two substances, bicarbonate — a pro-balance base that is transported by the CF transmembrane conductance regulator (CFTR, the gene with disease-causing mutations) — and protons that increase acidity.

Researchers found that the airway liquid of CF cells not only had lower amounts of bicarbonate due to problems in the workings of the CFTR protein, but also that a proton pump called ATP12A transported higher-than-usual amounts of protons.

Increased acidity also was linked to a higher amount of bacteria infecting the airways. Lowering airway liquid acidity in CF cells made them more resistant to S. aureus infection. Blocking ATP12A also caused a decrease in acidity, again making the cells more resistant to infection.

Another bicarbonate transporter, called pendrin, also was identified. Pendrin plays a key role in the acidification of the liquid airway of CF patients, and raising its levels lessened the liquid’s acidity and improved resistance to bacteria.

“Our data strongly suggest that CF cells fail to properly regulate [acidity] variations, and demonstrate a potential role for pendrin and ATP12A in [acidity]-dependent bacterial clearance capacity,” researchers wrote.

And, they suggested, normalizing the acidity of the airway liquid in newborns with CF could improve their resistance against S. aureus infection and slow progression of the disease.

“Translating this understanding into early [airway liquid acidity] normalization is now an exciting challenge, with prospects for improved clinical care,” the team concluded.