From the Journals

Mucus buildup precedes lung damage in children with CF



The buildup of mucus in the lungs was found to precede airway changes and infection in young children with cystic fibrosis (CF), according to a cross-sectional cohort study.


It has been difficult for researchers to pinpoint the mechanisms that initiate lung disease in people with CF, because it is challenging to study young people with the disease and “CF animal models often fail to recapitulate aspects of human CF disease and yield disparate findings,” wrote Charles R. Esther Jr., MD, of the division of pediatric pulmonology at the University of North Carolina at Chapel Hill and his colleagues in Science Translational Medicine.

The researchers studied 46 clinically stable young children (aged 3.3 years, plus or minus 1.7 years) with CF and 16 age-matched controls who did not have CF, but had respiratory symptoms (aged 3.2 years, plus or minus 2.0 years) using chest CT imaging and bronchoalveolar lavage fluid. BALF samples in CF patients were collected over 62 study visits and subsequently cultured for detection and quantification of pathogens. The children with CF were enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) program.

“We analyzed the relationships between airway mucus, inflammation, and bacterial culture/microbiome,” the researchers wrote.

BALF total mucin levels were higher in CF samples versus non-CF controls. In addition, Dr. Esther and his colleagues found that these results were the same regardless of infection status and that increased densities of mucus flakes were also seen in samples from the CF patients. “Elevated total mucin concentrations and inflammatory markers were observed in children with CF despite a low incidence of pathogens identified by culture or molecular microbiology. This muco-inflammatory state also characterized our CF population with the earliest lung disease [without substantial CT-defined structural changes] in the setting of little or no pathogen infection,” they wrote.

Based on the findings, the investigators postulated that the airways of children with CF may show distinct defects in the clearance of recently created mucins, which could contribute to early CF lung disease.

A key limitation of the study was the prophylactic use of intermittent antibiotics. As a result, bacterial infection could have contributed to the development of early CF lung disease.

“Agents designed to remove permanent mucus covering airway surfaces of young children with CF appear to be rational strategies to prevent bacterial infection and disease progression,” they concluded.

The study was supported by the National Heart, Lung, and Blood Institute; the North Carolina Translational and Clinical Sciences Institute; the National Health and Medical Research Council; and the Cystic Fibrosis Foundation. Two coauthors reported financial affiliations with Parion Sciences.

SOURCE: Esther CR et al. Sci Transl Med. 2019 Apr 3. doi: 10.1126/scitranslmed.aav3488.

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