Pathogenesis of chronic obstructive pulmonary disease

Abstract

The current paradigm for the pathogenesis of chronic obstructive pulmonary disease is that chronic airflow limitation results from an abnormal inflammatory response to inhaled particles and gases in the lung. Airspace inflammation appears to be different in susceptible smokers and involves a predominance of CD8+ T lymphocytes, neutrophils, and macrophages. Studies have characterized inflammation in the peripheral airspaces in different stages of disease severity. Two other processes have received considerable research attention. The first is a protease-antiprotease imbalance, which has been linked to the pathogenesis of emphysema. However, the hypothesis of an increased protease burden associated with functional inhibition of antiproteases has been difficult to prove and is now considered an oversimplification. The second process, oxidative stress, has a role in many of the pathogenic processes of chronic obstructive pulmonary disease and may be one mechanism that enhances the inflammatory response. In addition, it has been proposed that the development of emphysema may involve alveolar cell loss through apoptosis. This mechanism may involve the vascular endothelial growth factor pathway and oxidative stress.

Figure 1.

Concentrations of 8-isoprostane, a lipid peroxidation product, in exhaled breath condensate. Mean values are shown by horizontal bars. COPD = chronic obstructive pulmonary disease. Modified by permission from Reference 71.

Figure 2.

Correlation between lung function and levels of 4-hydroxy-2-nonenal (4-HNE), a lipid peroxidation product, in the lungs. Modified by permission from Reference 72.

Figure 3.

Rat lungs treated with SU5416 (SU), a vascular endothelial growth factor receptor blocker, show increased alveolar cell apoptosis, as quantified by an active caspase-3 assay. M40419 (M), a superoxide dismutase mimetic, has a protective effect on SU5416-induced apoptosis. CTL = control. Modified by permission from Reference 97.