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Title: Microbiome balance in sputum determined by PCR stratifies COPD exacerbations and shows potential for selective use of antibiotics
Authors: Haldar, Koirobi
Bafadhel, Mona
Lau, Kelvin
Berg, Adam
Kwambana, Brenda
Kebadze, Tatiana
Ramsheh, Mohammadali Yavari
Barker, Bethan
Haldar, Pranabashis
Johnston, Sebastian
Ketley, Julian M.
Brightling, Christopher E.
Barer, Michael R.
First Published: 25-Aug-2017
Publisher: Public Library of Science
Citation: PLoS ONE, 2017, 12 (8), e0182833
Abstract: BACKGROUND: While 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. METHODS: Phylogenetically 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. RESULTS: Cluster 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). CONCLUSIONS: The 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.
DOI Link: 10.1371/journal.pone.0182833
eISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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