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Title: Exacerbations, antibiotics and the airway microbiome in chronic lung disease
Author: Brill, Simon
ISNI:       0000 0004 7963 7783
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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This thesis investigates the airway microbiome in chronic obstructive pulmonary disease (COPD). The relationship of the airway microbiome to clinical disease characteristics and prophylactic antibiotic therapy is unknown, as are the ideal methods of community recruitment into clinical trials of COPD. Direct comparative data between bacterial culture and newer molecular techniques are also lacking. We used a randomised controlledantibiotic trial of patients with COPD to investigate these areas. During recruitment to this study we hypothesised that within primary care, different sources would have particular advantages when recruiting patients to clinical studies of COPD. We proposed that in stable COPD there would be aspects of the microbiome composition that would relate clinically to disease characteristics, and that when antibiotic therapy was given for three months there would be measurable changes in the microbiome as well as in bacterial resistance and clinical disease measures. We found that pulmonary rehabilitation and patient groups represented the most efficient and cost-effective way to recruit COPD patients. Our comparison between culture and molecular methods showed concordance between the techniques, but that different aspects of the microbiome are being assessed. Analysis of the microbiome at baseline showed that in one quarter of patients the COPD microbiome is dominated by the genus Haemophilus, predominantly Haemophilus influenzae, with greater levels of airway inflammation. Therapy with three months of moxifloxacin, but not azithromycin or doxycycline, was effective against placebo in reducing the burden of Haemophilus species with a concurrent reduction in inflammation. Antimicrobial resistance increased in all treatment groups. Our findings suggest that COPD patients whose microbiota is dominated by Haemophilus may derive particular benefit from prophylactic antibiotic therapy, although this drives antimicrobial resistance.
Supervisor: Wedzicha, Jadwiga ; Hurst, John Sponsor: National Institute for Health Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral