Could lower airway microbiota serve as a biomarker for CF progression?

Cystic fibrosis

By Nicola Garrett

4 Sep 2018

Young adults with cystic fibrosis with low microbiome diversity in their sputum have a greater risk of early end-stage lung disease, a novel study finds.

According to the researchers from the Canada their findings could be used to  identify patients with CF at increased risk of disease progression for more intensive monitoring and treatment.

In the study the researchers performed 16S rRNA gene sequencing of biobanked sputum samples collected prospectively over two decades from a cohort of 104 clinically stable young adults with CF.

Overall, the 17 individuals (16%) who subsequently progressed to end-stage lung disease were more likely to have sputum with low alpha diversity, dominated by specific pathogens including Pseudomonas.

Conversely, those with a diverse community, dominated by organisms such as Streptococcus, were more likely to have a milder clinical course, the study authors noted in their paper published in Thorax.

Multivariate analysis conducted by the authors showed that baseline lung function and alpha diversity were independent predictors of early end-stage lung disease.

According to the authors their findings supported large-scale collaborative multicentre studies evaluating the microbiome as a novel biomarker.

Prof Scott Bell

In an accompanying editorial, Professor Scott Bell from the Adult CF Centre at The Prince Charles Hospital in Brisbane and Laura Sherrard from the Queen’s University in Belfast, UK, said that novel biomarkers that identified patients at an increased risk of worse outcomes could help inform clinical decision making.

However, they noted that an issue with comparing ecological measures of lower airway microbiota to clinical outcomes was that significant correlations do not imply direct nor causal relationships.

“16S rRNA gene sequencing also does not reflect dynamic interactions that might occur in vivo between bacteria (and other micro-organisms), and the host which may influence the community composition and structure, immune response and ultimately, impact on disease progression,” they wrote.

Questions also remained such as: is it feasible to use biomarker testing of the lower airway microbiota? rRNA gene sequencing is laborious and expensive, they said. And they questioned the ideal timing of biomarker testing, suggesting that the period of transition from paediatric to adult care could be the ideal opportunity.

Lastly, they asked, did the respiratory sample type matter as adolescents were becoming increasingly healthier which could mean that in the future collection of expectorated sputum might be exceptional rather than the norm.

“Future studies of other cohorts (eg, younger cohorts, older cohorts and endpoints considered beyond 25 years of age) using the same techniques and parameters to replicate the key findings will be important to convince hospital laboratories and clinicians that lower airway microbiota ‘biomarkers’ are ready for implementation,” they concluded.

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