Time course of infective and inflammatory changes at exacerbation of COPD
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COPD is associated with recurrent episodes of exacerbations that lead to ibcreased morbidity and mortality. Exacerbations are associated with increased airway and systemic inflammation. This thesis examines the relationship between the infective and inflammatory changes at each exacerbation of COPD and clinical non-recovery and recurrence of exacerbations. Patients were recruited from the London COPD cohort and sampled retrospectively in the stable state, at exacerbation and after 7, 14 and 35 days. Clinical indices, airway and systemic inflammtion and lower airway bacteria were analysed at each vsist. Airway inflammation was assessed by sputum interleukin (IL)-6 and IL-8 levels, systemic inflammation was assessed by circulating leucocytes, serum C-reactive protein (CRP) and IL-6. Sputum bacteria were assessed by standard cultures and quantitative real time polymerase chain reaction (qr-PCR) The key finding were 1) the persistence of heightened airway and systemic inflammation was associated with clinical non-recovery at exacerbation 2) a higher level of serum CRP 14 days after an exacerbation was associated with a recurrent exacerbation within 50 days, 3) frequent exacerbators have reduced response to therapy and persistently high systemic inflammtion compared to infrequent exacerbatirs, 4) the presence of a significant relationship between the lower airway bacterial load and circualting leucocytes in stable COPD an 6) the detection of a potentially pathogenic micro-organism from sputum samples is higher by qr-PCR than by standard cultures. these new findings could form the basis of future therapeutic interventions and strategies for prevention of recurrent exacerbations. Further studies into the mechanisms for explaining the differences between frequent and infrequent excaerbators may help redduce the high burdeb due to disease. Finally refining the qr-PCR assay may help elucidate the complex links between lower airway bacteria and inflammation in COPD.
- Theses