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Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by persistent respiratory symptoms and airflow obstruction ( 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/or 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 products of combustion, cigarette smoking in the United States, and biomass fuels in some other countries. Host factors such as abnormal lung development and genetics can lead to COPD. 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 population thresholds of normality. Investigators in the COPDGene study recently proposed a multidimensional approach to COPD diagnosis, which is based on domains of environmental exposures, respiratory symptoms, imaging abnormalities, and physiologic abnormalities.

COPD is the fourth 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. Globally, there are an estimated 250 million individuals with COPD.


Airflow obstruction, the physiologic marker of COPD, can result from 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 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. 292-1) is more clearly defined than the pathogenesis of small airway disease. Pulmonary vascular destruction occurs in concert with small airway disease and emphysema.

FIGURE 292-1

Pathogenesis of emphysema. Upon long-term exposure to cigarette smoke in genetically susceptible individuals, lung epithelial cells and T and B lymphocytes recruit inflammatory cells to the lung. Biological pathways of protease-antiprotease imbalance, oxidant/antioxidant imbalance, apoptosis, and lung repair lead to extracellular matrix destruction, cell death, chronic inflammation, and ineffective repair. Although most of these biological pathways influence multiple pathobiological results, only a single relationship between pathways and results is shown. A subset of key molecules related to these biological pathways is listed.

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