Open AccessMicrobiome balance in sputum determined by PCR stratifies COPD exacerbations and shows potential for selective use of antibiotics
Author(s) -
Koirobi Haldar,
Mona Bafadhel,
Kelvin Lau,
Adam Berg,
Brenda Kwambana-Adams,
Tatiana Kebadze,
Mohammadali Yavari Ramsheh,
Bethan Barker,
Pranabashis Haldar,
Sebastian L. Johnston,
Julian M. Ketley,
Christopher E. Brightling,
Michael R. Barer
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0182833
Subject(s) - exacerbation , sputum , copd , medicine , antibiotics , gastroenterology , area under the curve , receiver operating characteristic , copd exacerbation , microbiology and biotechnology , biology , pathology , acute exacerbation of chronic obstructive pulmonary disease , tuberculosis
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 FEV 1 . 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.