Neutrophil cell subtype tied to lung function decline in stable CF

Mature low-density neutrophils are a white blood cell subtype

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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A dropper is poised over a petri dish alongside an aerial view of another petri dish filled with a sample.

Lung function decline in adults with stable cystic fibrosis (CF) was tied to high numbers of mature low-density neutrophils, a white blood cell subtype associated with inflammatory disorders, a study suggests.

While previous research showed that low-density neutrophils in CF children correlated with better lung function, the changes found in adult patients in this study may reflect disease progression and severity in a time-dependent manner, the researchers noted.

As a result, these immune cells might be a potential blood-based biomarker for lung disease progression in CF adults considered clinically stable, they added.

The study, “Association of low-density neutrophils with lung function and disease progression in adult cystic fibrosis,” was published in the Journal of Cystic Fibrosis.

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In CF, the buildup of thick mucus in the airways increases the risk of chronic airway infections, the primary cause of complications in CF.

Neutrophils are the most abundant type of infection-fighting immune cell. Despite large numbers of neutrophils deployed to the lungs during CF-related infections, they are unable to completely clear infections. As a result, they accumulate in the lungs, causing ongoing inflammation and tissue injury.

Neutrophils can be classified into subtypes based on their density. Normal-density neutrophils (NDNs) are the most abundant type of neutrophil and the most frequently studied. In contrast, low-density neutrophils (LDNs) are found in higher numbers in inflammatory diseases and are associated with disease severity and/or progression.

While LDNs have been reported in children with CF infected with Pseudomonas aeruginosa, a bacteria commonly found in the lungs of CF patients, LDNs correlated with better lung function. Still, in adults with CF, the occurrence and impact of LDNs remain unknown.

Researchers in Canada collected blood samples from 34 clinically stable CF patients, ages 18-59, of whom 12 were women, alongside 35 age- and sex-matched unaffected controls. LDNs were isolated, and their numbers were compared with controls and patients’ clinical parameters.

Blood tests revealed that CF patients had significantly more LDNs compared with controls, in whom mature LDNs were more abundant than immature cells.

CD14, a protein found at high levels on activated neutrophils, was elevated in both mature and immature cells than in controls. Also, immature CF LDNs produced higher levels of the marker CD33, a protein that is abnormally high in some blood cancers.

At the start of the study, there were no correlations between the total LDNs, mature LDNs, and immature LDNs with lung function. More total LDNs did correlate with older age, but not with mature and immature LDN counts.

Mature vs. immature LDNs

CF patients with more pronounced lung function decline, assessed up to five years before blood collection, had significantly higher numbers of mature LDNs. Also, those with the weakest lung function, and who experienced at least three exacerbations in the previous year (worsening lung symptoms requiring antibiotic treatment), had more mature LDNs than those without a history of exacerbations.

By contrast, better lung function correlated significantly with higher immature LDN counts.

“We identified clinically relevant, mature LDNs whose proportion in circulation negatively correlates with lung function decline and multiple [exacerbations] in adult CF patients that are clinically stable,” the researchers wrote.

“While further research is needed to determine the role of mature and immature LDNs in CF,” they added, “our observations indicate that mature LDNs are a potential indicator of ongoing disease progression in adult patients considered clinically stable.”