The role of airway infection in chronic obstructive pulmonary disease

Abstract

This. thesis examines the role of respiratory bacterial and viral infection in the natural history of Chronic Obstructive Pulmonary Disease. The rationale for this study is basedu pon previous data demonstratingt hat airway bacterial colonisationi s common in stable COPD and that bacterial and viral pathogens are commonly detected at exacerbations. The methodsu sed have involved the careful characterisationa nd clinical follow up of a cohort of patients with moderate to severe COPD in the stable state and at exacerbation. Sampling of airway and systemic compartments enabled the detection of respiratory pathogens and quantification of inflammation. Comparisons between clinical indices and evidence of infection were performed to determine the relationships between bacterial and viral infections and disease outcomes including lung function decline and exacerbation severity. The findings confirmed that lower airway bacterial colonisation is common in stable COPD and is associated with airway inflammation. They demonstrated for the first time a relationship between the degree of bacterial carriage and the rate of disease progression. This study has also described novel evidence for persistence of respiratorys yncytial virus in the lower airway and associationsw ith inflammation and lung function decline and impaired anti-viral immune responsesT. he combined role of human rhinoviral and bacterial infection at exacerbation has been studied and factors influencing responsesto exacerbationt herapy determinedw ith the importance of early initiation of treatment identified. The findings in this thesis indicate that both viral and bacterial pathogens may play an important role in the natural history of COPD and are therefore targets for potentially novel interventions. This work suggests that viral and bacterial infections and their interactions play an important role in modulating airway inflammation in stable disease and at exacerbation thus impacting on both disease progression and exacerbation severity. This work has provided a rationale for future investigation into the mechanisms underlying susceptibility to infection in this important disease.