Chemical Biology: Approaches to Drug Discovery and Development to Targeting Disease

Chapter 13: Chronic Obstructive Pulmonary Disease (COPD)

Peter J. Barnes

Imperial College, National Heart and Lung Institute, London, United Kingdom

Airway obstruction in chronic obstructive pulmonary disease (COPD) is caused by narrowing of small airways as a result of inflammation and fibrosis and the disruption of their alveolar attachments as a result of emphysema. COPD is characterized by a complex inflammatory disease process that increases as the disease progresses, which leads to increasing airflow limitation. Many inflammatory cells and mediators have now been implicated in the pathogenesis of COPD. Increased numbers of macrophages, neutrophils, T-lymphocytes (particularly CD8⁺ cells) and B-lymphocytes have been observed, as well as the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). Macrophages seem to play an important role in orchestrating the inflammatory process, which includes the recruitment of neutrophils and T-cells into small airways and lung parenchyma and the secretion of proteinases that lead to emphysema. A high level of oxidative and nitrative stress may amplify this inflammation through the reduction in histone deacetylase-2, which also results in corticosteroid resistance.

Chronic obstructive pulmonary disease (COPD) has now become a major global epidemic, and it is predicted to become the third leading cause of death and fifth leading cause of disability over the next decade [1]. The increase in COPD is a particular ...