Differences in Lung Bacteria Evident in CF, Like Disorder at Young Ages

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by Steve Bryson PhD |

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The bacterial composition within the airways of children with cystic fibrosis (CF) differs from those with primary ciliary dyskinesia (PCD), a disorder also characterized by mucus buildup and lung infections, a study reported.

Its researchers, who followed children with either disease for about one year, found airway bacterial diversity to also be highly individualized, supporting more tailored treatments in managing these patients.

The study, “Comparison of the airway microbiota in children with chronic suppurative lung disease,” was published in the journal BMJ Open Respiratory Research.

Mucus buildup in the airways, lung infections, and inflammation are hallmarks of CF, caused by the impaired flow of water and salts in and out of cells due to a faulty CFTR transport protein. These features are also reported in people with PCD, an inherited disorder stemming from mutations in genes necessary for cilia — finger-like projections that extend from the cell surface — that help to clear mucus from the airways.

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Both CF and PCD are characterized by acute and destructive lung infections accompanied by the production of pus.

Variation in sputum composition highlights the differences between CF and PCD, which may influence the type of microbes that grow in the airways. For unknown reasons, however, PCD rarely leads to the steep decline in lung function seen with CF.

Researchers in the U.K. decided, reportedly for a first time, to compare microbes found in CF and PCD patients’ airway samples.

“Understanding the variation in the microbiota between these two [diseases] … is important to further our understanding of microbiological processes when bacterial elimination is compromised and may lead to development of novel therapies,” the team at Imperial College London wrote.

They enrolled 31 children for each disease group, with mean ages between 9 and 10. Genetic analysis identified the bacteria present in regularly collected sputum samples or throat swabs, a confirmed surrogate for lung samples. Across both groups, the children were followed for a mean of 1.1 years.

“We hypothesised that the microbiota would differ between PCD and CF and would show differences between the two disease with age and clinical status,” they added.

Analysis confirmed this hypothesis. During the study period, the bacteria species Pseudomonas aeruginosa and Aspergillus fumigatus were more common in CF patients. Streptococcus pneumoniae and Haemophilus influenzae were more frequently found in children with PCD.

Streptococcus was the most common genus in both diseases — found in 55% of CF samples and 31% of those with PCD. Of note, the Streptococcus genus is a biological classification that encompasses different types of Streptococcus bacteria, such as Streptococcus pneumoniae.

Notably, the Haemophilus genus was less common in CF (3.2%) than PCD (20.5%) samples. Pseudomonas bacteria were the second most common genus in CF (8.1%) but were less frequent in PCD (1.2%). The diversity of bacteria within each sample (alpha diversity) was lower in CF than PCD.

In CF patients, an analysis of changes with aging in genetically related bacteria found two small but significant changes in abundance: Haemophilus decreased, while Actinomyces increased (genus of Actinobacteria bacteria). In PCD, Streptococcus significantly declined with age, while Haemophilus rose.

Most PCD patients as infants (age 6 months) had a high relative abundance of Streptococcus bacteria and a low abundance of Haemophilus (66.7% vs. 1.3%). Over time, Streptococcus decreased until age 5 (17.2%), while Haemophilus increased (55.8%). The reverse was seen from ages 6 through 9, but between 10 and 17 years old, Haemophilus again increased (79.3%).

In both CF and PCD samples, bacterial diversity within samples changed significantly with age. Bacterial richness — the number of different organisms — increased  in early childhood and peaked at age 4 in CF and age 7 for PCD children. In comparison, there is no significant difference in diversity between samples (beta diversity) with age.

A high degree of variability in the types of bacteria present in both diseases indicated airway microbes were specific in each individual.

The influence of clinical variables, pulmonary exacerbations, and antibiotics on airway microbes were also explored. Pulmonary exacerbations were defined as a sudden worsening of symptoms requiring intravenous (into-the-vein) antibiotics.

In CF children, all measures of alpha diversity — bacterial diversity within samples — were higher in those with occasional P. aeruginosa infection compared with those who had never had this infection. However, the growth of these bacteria during the study was significantly related to poorer alpha diversity.

The researchers also found greater alpha diversity in CF patients who carry the F508del, the most common disease-causing defect, compared to other CFTR mutations.

In PCD children, diversity was lower in H. influenzae-positive samples than those who had never tested positive.

No significant association was found between lung function and alpha and beta diversity for either disease, and no differences in oral or intravenous antibiotic treatments or preventative or nebulized antibiotics.

“In conclusion, we have demonstrated that the PCD microbiota differs from that of CF,” the inevstigators wrote. “The airway microbiota is highly individual in these diseases, further strengthening arguments for personalised approaches to patient management.”

“Further study to better understand this relationship may lead to new therapeutic approaches,” the team added.