• COPD ÀÜ Mechanisms
• COPD Pathology

The clinical burden of COPD remains a global health challenge that is not being met by current preventive and therapeutic strategies.1 For decades, the key features of this heterogeneous condition have been studied and the associations between airways disease, emphysema, systemic illness and tobacco smoking have been explored. Despite significant advances in our understanding of the aetiology of important clinical aspects of disease including the heterogeneity of airway inflammation2 and the pathogenesis of exacerbations,3 there remain significant gaps in our understanding of the mechanisms underlying key facets of the condition including the origins of emphysema.

A number of potential mechanisms of disease have been proposed to explain the progressive loss of lung parenchyma in response to tobacco and biomass smoke exposure.4 Focus on protease imbalance and neutrophilic inflammation5 on one hand and T-cell-mediated pathology on another6 have offered some insights into contributory mechanisms but to date have failed to offer a route to disease modifying therapy or even convincing biomarkers of disease progression.

Furthermore, it is increasingly apparent that COPD is both a pulmonary and systemic condition, with a significant contribution to the associated morbidity and mortality driven by an increased incidence and severity of cardiovascular disease.7 It has been recognised that endothelial pathology is a key component of COPD, both in the manifestation of a systemic disease process and in the development of discrete lung pathology …