Rehabilitation Systems

Recently, chronic obstructive pulmonary disease (COPD) has gained interest as a major public health concern and is currently the focus of intense research because of its persistently increasing prevalence, mortality, and disease burden. COPD was responsible for more than 2.5 million deaths worldwide in the year 2000 alone and currently ranks as the fourth leading cause of death in the United States, surpassed only by heart disease, cancer, and cerebrovascular disease. Furthermore, COPD is projected to have the fifth leading burden of disease worldwide by the year 2020. COPD is one of the leading causes of disability worldwide and is the only disease for which the prevalence and mortality rates continue to rise.

This document presents a concise overview of COPD. We address its definition, prevalence and epidemiology, pathology and pathophysiology, diagnosis, therapy, and outcomes. Also, because of recent insights regarding the relation between COPD and sleep disorders, we include a discussion on sleep and COPD.

Definitions
COPD is broadly defined and encompasses several clinical and pathologic entities, namely emphysema and chronic bronchitis. Evidence of airflow obstruction that is chronic, progressive, and for the most part fixed, characterizes COPD. Notwithstanding the presence of irreversible airflow obstruction in COPD, most individuals (∼60% to 70%) demonstrate a reversible component of airflow obstruction when tested repeatedly.

Emphysema is specifically defined in pathologic terms as ―alveolar wall destruction with irreversible enlargement of the air spaces distal to the terminal bronchioles and without evidence of fibrosis.‖
Chronic bronchitis is defined as ―productive cough that is present for a period of three months in each of two consecutive years in the absence of another identifiable cause of excessive sputum production.

Whereas the American Thoracic Society (ATS), British Thoracic Society (BTS), and European Respiratory Society (ERS) definitions of COPD emphasize chronic bronchitis and emphysema, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposes a definition of COPD that focuses on the progressive nature of airflow limitation and its association with abnormal inflammatory response of the lungs to various noxious particles or gases. According to the GOLD document, COPD is defined as ―a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.

Pathogenesis and Pathology
As indicated in the definition of emphysema, the pathologic hallmark is elastin breakdown with resultant loss of alveolar wall integrity. This process is triggered by the exposure of a susceptible individual to noxious particles and gases. Cigarette smoke remains the main causative agent, involved in more than 90% of cases; however, other gases and particles have been shown to play a role in pathogenesis, which is a result of an inflammatory process. In contrast to the eosinophilic inflammation seen in asthma, the predominant inflammatory cell is the neutrophil. Macrophages and CD8+ T lymphocytes are increased in the various parts of the lungs, and several mediators, including leukotriene B4, interleukin 8, and tumor necrosis factor, contribute to the inflammatory process.

Oxidative stress is regarded as another important process in the pathogenesis of COPD, and altered protease/antiprotease balance, at least in individuals with severe deficiency of alpha-1 antitrypsin, has been shown to predispose to a panacinar form of emphysema. Individuals with severe deficiency of alpha-1 antitrypsin may develop emphysema at an early age (e.g., by the fourth decade), in contrast to the ―usual‖ emphysema, which typically begins in the sixth decade. The pathologic hallmark of chronic bronchitis is an increase in goblet cell size and number that leads to excessive mucus secretion. Airflow obstruction and emphysematous change are frequent but not universal accompaniments. When COPD is complicated by hypoxemia, intimal and vascular smooth muscle thickening may cause pulmonary hypertension, which is a late and poor prognostic development in COPD.

Diagnosis
The diagnosis of COPD is suggested by findings on history or physical examination, or both, and is confirmed by laboratory tests, usually with a supportive risk factor (e.g., familial COPD or cigarette exposure, or both). Spirometry is indispensable in establishing the diagnosis because it is a standardized and reproducible test that objectively confirms the presence of airflow obstruction. Characteristically, spirometry shows a decreased forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) ratio. Evidence of reversible airflow obstruction, defined as a post-bronchodilator rise of FEV1 and/or FVC by 12% and 200 mL, is present in up to two thirds of patients with serial testing. Measurement of the diffusing capacity for carbon monoxide (DLCO) may help differentiate between emphysema and chronic bronchitis. Specifically, in the context of fixed airflow obstruction, a decreased diffusing capacity indicates a loss of alveolar-capillary units, which suggests emphysema. Deficiency of α1 antitrypsin is an uncommon cause of emphysema that continues to be under-recognized by practicing clinicians. The clinical recognition of patients with this condition is also based on clinical suspicion, but as outlined in the American Thoracic Society/European Respiratory Society (ATS/ERS) evidence-based standards document, specific circumstances should prompt suspicion of α1-antitrypsin deficiency. They include emphysema occurring in a young individual (age 45 or younger) or without obvious risk factors (e.g., smoking or occupational exposure) or with prominent basilar emphysema on imaging, necrotizing panniculitis, antineutrophil cytoplasmic antibody (C-ANCA)–positive vasculitis, bronchiectasis of undetermined etiology, otherwise unexplained liver disease, or a family history of any one of these conditions, especially siblings of PI*ZZ individuals.

The most common symptoms and signs include cough, dyspnea on exertion, and increased phlegm production. Additional signs and symptoms include wheezing, prolonged expiration with pursed-lip breathing, barrel chest, use of accessory muscles of breathing and, in advanced cases, cyanosis, evidence of right heart failure, and peripheral edema. A chest radiograph (CXR) is usually obtained to exclude other etiologies but may show hyperinflation and flattening of the diaphragms with increased retrosternal space on the lateral view, and hyperlucency reflecting oligemia. The chest radiograph is an insensitive test for diagnosing emphysema and is abnormal only when emphysema is relatively advanced. In contrast, high-resolution computed tomography (CT) scanning is far more sensitive and specific than CXR for diagnosing emphysema and readily identifies bullae and blebs that are the consequences of alveolar breakdown. However, save its role in selecting the proper candidate for lung volume reduction surgery (LVRS), the additional data from CT rarely alter therapy, making CT scanning not indicated for routine clinical use.

Classification of Severity
Because the degree of FEV1 reduction has prognostic implications and correlates with mortality and morbidity, a staging system based on the degree of airflow obstruction has been proposed by the different societal guidelines. As reviewed in, staging of disease severity, four groups—the ATS, the ERS, the BTS, and GOLD—have developed staging systems for COPD based on the value of FEV1 percent predicted. All systems propose three-stage classifications of COPD, although the FEV1 criteria vary among systems.

Staging of Disease Severity
Disease Severity
FEV1 Predicted

Stage 0: at risk: Normal
Chronic symptoms (cough, sputum production)

Stage I: mild - FEV1 Predicted
≥80%
With or without chronic symptoms

Stage II: moderate - FEV1 Predicted
50%-79%
With or without chronic symptoms

Stage III: severe - FEV1 Predicted
30%-49%
With or without chronic symptoms

Stage IV: very severe - FEV1 Predicted
<30% or <50% with chronic respiratory failure

ATS, American Thoracic Society; BTS, British Thoracic Society; ERS, European Respiratory Society; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease.