Abstract
BackgroundWhile a subgroup of patients with exacerbations of chronic obstructive pulmonary disease (COPD) clearly benefit from antibiotics, their identification remains challenging. We hypothesised that selective assessment of the balance between the two dominant bacterial groups (Gammaproteobacteria (G) and Firmicutes (F)) in COPD sputum samples might reveal a subgroup with a bacterial community structure change at exacerbation that was restored to baseline on recovery and potentially reflects effective antibiotic treatment.MethodsPhylogenetically specific 16S rRNA genes were determined by quantitative real time PCR to derive a G:F ratio in serial sputum samples from 66 extensively-phenotyped COPD exacerbation episodes.ResultsCluster analysis based on Euclidean distance measures, generated across the 4 visit times (stable and exacerbation day: 0,14 and 42) for the 66 exacerbation episodes, revealed three subgroups designated HG, HF, and GF reflecting predominance or equivalence of the two target bacterial groups. While the other subgroups showed no change at exacerbation, the HG cluster (n = 20) was characterized by G:F ratios that increased significantly at exacerbation and returned to baseline on recovery (p<0.00001); ratios in the HG group also correlated positively with inflammatory markers and negatively with FEV1. At exacerbation G:F showed a significant receiver-operator-characteristic curve to identify the HG subgroup (AUC 0.90, p<0.0001).ConclusionsThe G:F ratio at exacerbation can be determined on a timescale compatible with decisions regarding clinical management. We propose that the G:F ratio has potential for use as a biomarker enabling selective use of antibiotics in COPD exacerbations and hence warrants further clinical evaluation.
Highlights
Chronic obstructive pulmonary disease (COPD) presents a major and increasing disease burden in both well- and poorly-resourced settings [1]
Cluster analysis based on Euclidean distance measures, generated across the 4 visit times for the 66 exacerbation episodes, revealed three subgroups designated high Gammaproteobacteria (HG), High Firmicutes subgroup (HF), and Balanced Gammaproteobacteria Firmicutes subgroup (GF) reflecting predominance or equivalence of the two target bacterial groups
We propose that the G:F ratio has potential for use as a biomarker enabling selective use of antibiotics in chronic obstructive pulmonary disease (COPD) exacerbations and warrants further clinical evaluation
Summary
Chronic obstructive pulmonary disease (COPD) presents a major and increasing disease burden in both well- and poorly-resourced settings [1]. The recently developed capacity to profile microbial communities through sequencing of 16S rRNA gene libraries allows us to analyse relationships between the sputum microbiome and clinical status and test more complex hypotheses concerning the causation of COPD exacerbations than those associated with single pathogens. Increases in the proportion of Moraxella sequences were present at exacerbation in ~40% of episodes while particular features of the community structure both discriminated between exacerbations designated eosinophilic and bacterial exacerbations and showed dependence on the proportion of Haemophilus sequences present. These community structure profiles raised interesting possibilities concerning the pathogenesis of exacerbations, such analyses are too resource-intensive to be deployed in day to day clinical practice. We hypothesised that selective assessment of the balance between the two dominant bacterial groups (Gammaproteobacteria (G) and Firmicutes (F)) in COPD sputum samples might reveal a subgroup with a bacterial community structure change at exacerbation that was restored to baseline on recovery and potentially reflects effective antibiotic treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
