Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease

Definition

COPD, or chronic obstructive pulmonary disease, is a progressive disease that makes it hard to breathe. "Progressive" means the disease gets worse over time. COPD can cause coughing that produces large amounts of mucus (a slimy substance), wheezing, shortness of breath, chest tightness, and other symptoms. Cigarette smoking is the leading cause of COPD. Most people who have COPD smoke or used to smoke. Long-term exposure to other lung irritants, such as air pollution, chemical fumes, or dust, also may contribute to COPD.

Etiology

Cigarette smoking is the primary risk factor in most countries, although only about 15% of smokers develop clinically apparent COPD; an exposure history of 40 or more pack-years is especially predictive. Smoke from burning biomass fuels for indoor cooking and heating is an important contributing factor in developing countries. Smokers with preexisting airway reactivity (defined by increased sensitivity to inhaled methacholine), even in the absence of clinical asthma, are at greater risk of developing COPD than are those without. Low body weight, childhood respiratory diseases, passive cigarette smoke exposure, air pollution, and occupational dust (eg, mineral dust, cotton dust) or chemical (eg, cadmium) exposure contribute to the risk of COPD but are of minor importance compared with cigarette smoking (Weitzenblum et al, 1995).

Genetic factors also contribute. The best-defined genetic disorder is a1-antitrypsin deficiency (see Chronic Obstructive Pulmonary Disease (COPD): a1-Antitrypsin Deficiency), which is an important cause of emphysema in nonsmokers and influences susceptibility to disease in smokers. Polymorphisms in microsomal epoxide hydrolase, vitamin D-binding protein, IL-1ß, IL-1 receptor antagonist, phospholipase A2, matrix metalloproteinase 9, and ADAM-33 genes are all associated with rapid decline in forced expiratory volume in 1 sec (FEV1) in selected populations (Vestbo, 2006).

Inhalational exposures trigger an inflammatory response in airways and alveoli that leads to disease in genetically susceptible people. The process is thought to be mediated by an increase in protease activity and a decrease in antiprotease activity (see Chronic Obstructive Pulmonary Disease (COPD): a1-Antitrypsin Deficiency). Lung proteases, such as neutrophil elastase, matrix metalloproteinases, and cathepsins, break down elastin and connective tissue in the normal process of tissue repair. Their activity is balanced by antiproteases, such as a1-antitrypsin, airway epithelium-derived secretory leukoproteinase inhibitor, elafin, and matrix metalloproteinase tissue inhibitor. In people with COPD, activated neutrophils and other inflammatory cells release proteases as part of the inflammatory process; protease activity exceeds antiprotease activity, and tissue destruction and mucus hypersecretion result (Petty TL, 1998). Neutrophil and macrophage activation also leads to accumulation of free radicals, superoxide anions, and hydrogen peroxide, which inhibit antiproteases and cause bronchoconstriction, mucosal edema, and mucous hypersecretion. Neutrophil-induced oxidative damage, release of profibrotic neuropeptides (eg, bombesin), and reduced levels of vascular endothelial growth factor may contribute to apoptotic destruction of lung parenchyma. Infection, in conjunction with cigarette smoking, may amplify progression of lung destruction. The inflammation in COPD increases with increasing disease severity, and, in severe (advanced) disease, inflammation may not resolve completely with smoking ...