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Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by persistent respiratory symptoms and airflow limitation that is not fully reversible (http://www.goldcopd.com/). COPD includes emphysema, an anatomically defined condition characterized by destruction of the lung alveoli with air space enlargement; chronic bronchitis, a clinically defined condition with chronic cough and phlegm; and small airway disease, a condition in which small bronchioles are narrowed and reduced in number. The classic definition of COPD requires the presence of chronic airflow obstruction, determined by spirometry, that usually occurs in the setting of noxious environmental exposures—most commonly cigarette smoking. Emphysema, chronic bronchitis, and small airway disease are present in varying degrees in different COPD patients. Patients with a history of cigarette smoking without chronic airflow obstruction may have chronic bronchitis, emphysema, and dyspnea. Although these patients are not included within the classic definition of COPD, they may have similar disease processes. Respiratory symptoms and other features of COPD can occur in subjects who do not meet a definition of COPD based only on airflow obstruction determined by spirometric thresholds of normality.
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COPD is the third leading cause of death and affects >10 million persons in the United States. COPD is also a disease of increasing public health importance around the world. Estimates suggest that COPD will rise to the third most common cause of death worldwide by 2020.
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Airflow limitation, a major physiologic change in COPD, can result from small airway disease and/or emphysema. Small airways may become narrowed by cells (hyperplasia and accumulation), mucus, and fibrosis, and extensive small airway destruction has been demonstrated to be a hallmark of advanced COPD. Although the precise biological mechanisms leading to COPD have not been determined, a number of key cell types, molecules, and pathways have been identified from cell-based and animal model studies. The pathogenesis of emphysema (shown in Fig. 286-1) is more clearly defined than the pathogenesis of small airway disease. Pulmonary vascular destruction occurs in concert with small airway disease and emphysema.
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The dominant current paradigm for the pathogenesis of emphysema comprises a series of four interrelated events: (1) Chronic exposure to cigarette smoke in genetically susceptible individuals triggers inflammatory and immune cell recruitment within large and small airways and in the terminal ...