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Plenary Lecture 11: The good the bad and the irrelevant. Sequential analyses of the sputum microbiome in patients with Chronic Obstructive Pulmonary Disease

Presented by: 
M Barer University of Leicester
Thursday 27th November 2014 - 14:35 to 15:10
INI Seminar Room 1
Co-authors: Koirobi Haldar (University of Leiceister), Mona Bafadhel (University of Oxford), Chris Brightling (University of Leiceister)

COPD is a chronic respiratory disease associated with progressive deterioration of lung function and eventually death from respiratory failure; chronic exposure to smoke is the major aetiological risk factor and the disease is a major WHO priority. COPD patients have excess production of mucus in their lower airways and this is coughed up as sputum which supports an abundant and diverse microbiome. The course of the disease is characterised by exacerbations in which cough and sputum production increase and lung function worsens. The causes of COPD exacerbations are hotly debated and are likely to be multiple. The view that infections, attributable to one or more microbial pathogen, are the primary cause of exacerbations is widely accepted by physicians and sanctioned by the almost universal use of antibiotics. However, rigorous evidence in support of this view is lacking. We have conducted the first sequential study of the sputum microbiome in COPD patients with samples taken when stable, at the time of exacerbation (prior to antibiotics) then 2 and six weeks later, when all had recovered from the episode. Microbiome profiling was based on Roche 454 sequencing of 16S-rDNA amplicons. With the exception of a small group of virus positive exacerbations the events could not be explained by the arrival or increased abundance of recognised pathogens. Microbiome analyses revealed a high frequency of 20 different phyla in most samples but consistent dominance of Proteobacteria and Firmicutes. No clear pattern with respect to composition or diversity of the microbiome was associated with exacerbations. However, cluster analysis revealed a subgroup of exacerbations in which disturbance of the ratio between Proteobacteria and Firmicutes occurred and subsequently returned to the stable value following therapy. We propose that this subgroup may be patients who need antibiotics while they are unnecessary or even harmful for patients whose microbiomes did not show this pattern.

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University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons