Cystic Fibrosis Bacterial Load Initiates in The Course of First Years of Life

In a new study published in PLoS Pathogens, performed in UNC School of Medicine, researchers discovered for the first time that the lungs’ bacterial population changes in the first few years of life as respiratory infections and inflammation sets in. This research gives a way to expect the onset of lung disease in children with Cystic Fibrosis and shows a bigger role for preventive healing procedures, including hypertonic saline.

“Lung signs and symptoms in children with CF are likely due to a probably because of an increased burden of bacteria,” said study senior author Matthew Wolfgang, Ph.D., Associate professor of microbiology and immunology. “This implies there’s a possibility for early intervention that could dramatically increase the quality of life for these kids.”

CF impacts approximately 70,000 humans globally and is most common in children of Northern European ethnicity – about one of every 2,500 births. The disease is caused by a dysfunctional model of the CFTR gene that encodes the CFTR protein. In the absence of this protein, mucus becomes dehydrated and thick – a sanctuary for microorganism – leading to repeated infections, inflammation, and finally structural damage to lungs and upper airway tissues. The life expectancy of CF patients is about 40 years.

This is a microscopic image of Staphylococcus aureus, a problematic pathogen that infects the airways of children with cystic fibrosis. (CREDIT
Wolfgang Lab, UNC School of Medicine)

Most CF studies were accomplished in adults and older children due to which how and when inflammation, bacterial infections, and lung damage begins not completely known. For increasing the understanding of this query, researchers examined the DNA of the bacteria in samples of lung-lining fluid gathered from young youngsters as part of an ongoing Australian project called AREST CF.

“It’s challenging and rare to get access to such samples,” said Wolfgang, member of the UNC Marsico Lung Institute. “Here in the United States, we don’t perform bronchoscopies on children diagnosed with CF if they don’t yet have clinical symptoms.”

The UNC scientists showed that there were little or no indication of bacteria in most of the samples from CF infants who were less than a year old.

“If there was no significant evidence of bacteria, there was also no sign of inflammation, and the child generally appeared healthy,” said Wolfgang.

In the children between ages one and two, the pattern was different: many samples contained a significant amount of bacterial DNA – from the same bacterial species that normally populate the mouth and throat. These bacteria are not typically regarded as lung pathogens.

“We can’t go so far as to say that these kids have active infections, but clearly there’s a significant increase in the bacterial burden in their lungs, and we know these bacteria provoke inflammation,” said Wolfgang.

They also observed increasing evidence of more worrisome bacteria, particularly Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae in the sample of children of age three to five. samples these bacteria which are commonly found in older CF patients with more severe lung disease. The molecular signs of inflammation increased as the bacterial load aggravated. Also, lung X-ray studies of the children showed the mounting signs of structural lung disease as the bacterial load increased.

“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.

During their research, they observed that Many of the bacterial species in the young children with CF, were “anaerobic” microbes that bloom in conditions of very low oxygen and anticipated that the dehydrated, thickened CF lung mucus creates pockets of low oxygen in lung tissues.

“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 species.”

Medical doctors already deliver preventive antibiotics to young children in Australia, Germany, and the United Kingdom. however, Wolfgang stated that the youngsters in the AREST CF observe, who had been treated with antibiotics till the age of, still showed a clear progression of bacterial burden and irritation. “it is able to be that other healing strategies, consisting of thinning mucus, may be greater a success,” he stated.

Wolfgang and associates on the UNC Marsico Lung Institute now wish to do a similar, long-term study investigating the lung bacteria of individual children and the changes in these “bacteriomes” over numerous years. The researchers need to assess the effectiveness of an early mucus-thinning intervention, for example, hypertonic saline – salt water delivered via inhaler – which is already used to hydrate mucous in older CF sufferers.


The BioScientist

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