This thesis examines novel aspects of exacerbations and chronic bronchitis spanning across the spectrum of chronic obstructive pulmonary disease (COPD). Both are important to study since they are implicated in the progression, morbidity and mortality of COPD. This thesis presents work from a recently recruited, novel longitudinal patient cohort dedicated to the serial sampling of individuals at risk of developing COPD (10pyh, 30-45yrs). It describes the characteristics of Early COPD in this group and the exacerbation events that they exhibit. This is a new approach to understanding the pathogenesis which underpins COPD development. To date, the majority of COPD studies attempting to examine the concept of Early COPD have included populations with mean ages older than 60 years1 which inform on late “mild disease as opposed to “early disease”.2

The methodology involved using symptom and treatment diary cards to record an increase in cardinal symptoms associated with an AECOPD. Patients were then seen clinically and data was compared to their baseline state. It found that CT changes consistent with Early COPD are more common than obstructive spirometry . It went on to show that exacerbation events in the Early COPD cohort may exhibit modest inflammatory changes but do find corresponding symptomatic and pathophysiological changes. There is evidence that a proportion do not fully recover and further work is required to ascertain the effect of these events on the development of established COPD.

Whilst examining the effect of intermittent bronchitis on COPD progression over a 9-year period in participants of the London exacerbation cohort, this study concluded that, the identification of chronic bronchitis through disease burden questionnaires can be objectively validated with sample tracking data. This thesis found that the higher percentage of baseline visits with sputum collected, the faster FEV1 declined.

Finally, this thesis presents the effect of retreatment in incompletely recovered AECOPD. This randomized, placebo control trial found no benefit of treatment with ciprofloxacin of exacerbations with persistent respiratory symptoms or a raised CRP (>=8 mg/dl) at 14 days post exacerbation onset. This suggests that non-recovered exacerbations which may lead to hospital readmission potentially need to be targeted with anti-inflammatory therapies and further research is now warranted to investigate exacerbation recovery.