A lungs infected over and over again with bacteria that lead to repeated inflammation and shorten life due to cystic fibrosis (CF). The University of North Carolina School of Medicine has now demonstrated for the first time that the lungs’ bacterial populations change in the first few years of life when respiratory infections and inflammation occur. Researchers published their findings in PLoS Pathogens, which offers a prediction tool to identify children who are likely to develop lung disease and a suggestion that hypertonic saline might hold more promise as a preventive bactericide for these children. The fact that early intervention could dramatically increase the quality of life of these kids indicates the possibility of a dramatic improvement.” CF affects about 70,000 people worldwide, and is most common in children of north European descent – about one child in every 2,500 born. There is a dysfunctional version of the CFTR gene that encodes the CFTR protein that causes this disease to develop. It is estimated that one-fifth of CF patients will live to the age of 40 because without this protein, mucus becomes dehydrated and thick, allowing bacteria to thrive, leading to repeated infections, inflammation, and eventually structural damage to the lungs and upper airways. As many CF studies have been carried out in adults and older children, little is known about how and when inflammations, bacterial infections, and lung damage begin in cases of CF. As part of an ongoing Australian project called AREST CF, Wolfgang and colleagues examined bacterial DNA in samples of lung lining fluid gathered from young children to shed more light on that question.

Wolfgang, a member of the UNC Marsico Lung Institute, said that access to such samples is challenging and rare. In the United States, we do not perform bronchoscopies on children diagnosed with CF if they do not already have clinical symptoms.” The UNC researchers found that most of the samples from CF children who were under a year old showed no evidence of bacterial contamination. There was no sign of inflammation and no evidence of bacteria when the child did not have significant evidence of bacteria,” Wolfgang said. In the children between the ages of one and two, the picture was different. A significant amount of bacterial DNA was present in nearly all samples — from the same species that normally colonize Bacteria such as these are usually not associated with lung disease. There is a significant increase in the amount of bacteria in the lungs of children age three to five, and we know these bacteria have an effect on inflammation. In older children with more severe lung disease, these bacteria are usually elevated. A worsening of the bacterial burden was accompanied by increasing molecular signs of inflammation. As the levels of bacterial burden increased, the X-rays of the children’s lungs showed that structural lung disease had become more prevalent. Wolfgang said, “It suggests that lung bacterial infections may start earlier than we expected in children with CF and that these infections may act as the first drivers of structural lung disease.” Most of the bacterial species found in young children with CF thrived in very low oxygen conditions. As a result of this dehydration and thickening of CF lung mucus, air pockets with low oxygen levels were found

Wolfgang noted that therapies that break up mucus in young children might be beneficial to them. These therapeutic approaches could delay bacterial growth, as well as the shift towards more pathogenic bacteria. Medical practitioners already administer preventive antibiotics to young children in Australia, Germany, and the United Kingdom. But Wolfgang noted that the children in the AREST CF study, when treated with antibiotics until they were two, continued to have a bacterial burden and inflammation as their bodies aged. It may be that other therapeutic strategies, such as thinning mucus, are more effective, Wolfgang said. Wolfgang and colleagues at the UNC Marsico Lung Institute hope to conduct a long-term study of lung bacteria in individual children and their changes over the course of A study has emerged that aims to assess the efficacy of early interventions to thin mucus, for example using hypertonic saline inhalers to deliver salt water, which is already used to hydrate CF mucus in older Marianne S. and Peter W. also contributed to the study as co-first authors. Bryan T. Munhlenbach, MD, an associate professor of pediatrics at UNC School of Medicine, and Katherine M. UNC health researcher Dr. Zorn conducted the study with funding from the Cystic Fibrosis Foundation and the National Institutes of Health. Several samples used in this study were collected thanks to funding from Australia’s National Health and Medical Research Council Centre for Research Excellence.