Chronic obstructive pulmonary disease (COPD) is defined by irreversible airflow limitation, usually caused by exposure to noxious particles or gases. COPD patients suffer from chronic daily symptoms, and may occasionally suffer acute exacerbations – episodes in which there is a worsening of symptoms above day-today levels. Exacerbation aetiology is variable and controversial, although infection and air pollution are believed to play a part. Certain bacterial pathogens, known as typical airway bacteria, are found with high prevalence in individuals at exacerbation. The burden of other airway bacteria is currently ill-defined. This study initially compared microbiological culture with quantitative PCR for detection of three commonly identified airway bacteria in COPD, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis (typical airway bacteria). Quantitative PCR was utilised to establish prevalence and load of these species at stable, exacerbation and exacerbation recovery states. Typical airway bacterial prevalence and load was assessed against a range of clinical factors in COPD. Additional quantitative PCRs examined the prevalence and load of atypical airway bacteria (Chlamydophila pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae) and the entire bacterial microflora of the lungs. My original contribution to knowledge is that higher load of typical airway bacteria is associated with higher levels of systemic inflammation and airflow limitation in both stable and exacerbated COPD. For the first time it has also been demonstrated that airway microbiome load is not associated with airflow limitation or systemic inflammation changes, providing evidence that typical airway bacteria in particular are contributing to disease severity. Atypical airway bacteria prevalence in COPD was negligible. The investigations in this thesis highlight the need for rapid antibiotic therapy in exacerbations where typical airway bacteria presence is suspected or confirmed. Furthermore, prophylactic antibiotic therapy should be considered for stable COPD patients with confirmed typical airway bacterial presence, as a means of reducing inflammation and airflow limitation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:626527 |
| Date | January 2014 |
| Creators | Garcha, D. S. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1425774/ |
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