Changes in bacteria present in the lower respiratory tract during the first years of life may be indicative of early progression of lung disease in cystic fibrosis (CF) patients, according to researchers at the University of North Carolina School of Medicine.
The finding was reported in the study, “Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children,” published in the journal PLoS Pathogens.
“Lung symptoms in kids with CF are likely due to an increased burden of bacteria,” Matthew Wolfgang, PhD, associate professor of microbiology and immunology at UNC Chapel Hill and senior author of the study, said in a news release.
“This implies there’s an opportunity for early intervention that could dramatically increase the quality of life for these kids,” he added.
Cystic fibrosis lung disease is characterized by persistent airway infections by complex microbial communities. These often consist of a mixture of commensal, beneficial, but also potentially harmful microorganisms that are normally associated with the oral cavity.
Until now, little was known about the development of these complex bacterial populations and their relationship to the progression of CF lung disease.
The UNC research team analyzed the bacterial content in 46 bronchoalveolar lavage (BAL) samples obtained from clinically stable CF infants and children, ages 3.5 months to 5 years, who underwent a bronchoscopy to evaluate the lung’s structure. This procedure was undertaken as part of the AREST CF study, based in Australia.
“It’s challenging and rare to get access to such samples,” Wolfgang said. “Here in the United States, we don’t perform bronchoscopies on children diagnosed with CF if they don’t yet have clinical symptoms.”
The team found that the majority of cystic fibrosis patients who were younger than 12 months old had few to no signs of bacteria in their lungs. But as they got a little older, CF children started to show increased signs of bacteria that are commonly found in the mouth and throat populating the lungs. Although these bacteria are not commonly associated with human disease, they were found to trigger inflammation in the lungs of CF children ages 1 to 2 years old.
In children ages 3 to 5, the oral-like bacteria population was also found in the lungs, but potentially harmful bacteria that are commonly associated with poorer prognosis in CF were also identified, including Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenza.
As the bacterial burden increased, the children had worse lung inflammation and structural damage.
“This tells us lung bacterial infections start much earlier than we had expected in children with CF, and these infections are likely the earliest drivers of structural lung disease,” Wolfgang said.
Some of the children included in the study received preventive antibiotics starting at a very young age. But these did not prevent the progressive increase in bacteria burden.
Most of the species of oral-like bacteria identified in the early stages were anaerobic microbes, which means they live in very low oxygen levels and may proliferate in thickened mucus found in the lungs of cystic fibrosis patients.
“Therapies aimed at breaking up mucus very early in life might be very beneficial to these kids,” Wolfgang said. “These therapies could postpone the increase in bacterial burden, including the shift towards the more pathogenic [harmful] species.”
The UNC team at Chapel Hill is planning to continue this study and address the effectiveness of an early mucus-thinning intervention, such as the use of hypertonic saline, which is already used to hydrate the airways in older CF patients.
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