[New concepts in the pathogenesis and pathophysiology of COPD]

Chronic obstructive pulmonary disease (COPD) is characterized by the progressive, partially reversible air flow limitation which occurs in association with a chronic inflammatory reaction triggered by smoking or other inhalation noxes in predisposed subjects. Genetic predisposition and /or latent adenoviral infections are responsible for the exacerbation and perpetuation of the inflammatory response despite smoking cessation. Inflammation is further aggravated by a process of chromatinic remodelling which amplify the expression of pro-inflammatory genes. Besides the role of macrophages, neutrophils and /CD8+ T lymphocytes, the involvement of dendritic cells, epithelial cells and eosinophils within the airway inflammation has also been reported. The other two contributors to the COPD pathogenesis are the oxidative stress and the proteases-antiproteases imbalance. Both processes together with the inflammatory one are responsible for the parietal remodelling of the bronchioles and the appearance of emphysema, the latter being aggravated by the apoptosis of the alveolar cells. Another important pathophysiological concept within the natural evolution of COPD is the pulmonary endothelial dysfunction which might be responsible for the arterial hypoxemia and pulmonary hypertension in these patients. The abnormal inflammatory response and the high oxidative stress are also present at the extrapulmonary level, thus explaining the systemic character of the disorder.