The World Health Organization (WHO) estimates that 210 million people have chronic obstructive pulmonary disease (COPD) worldwide, with more than 3 million dying from the disease annually. COPD is the fourth leading cause of mortality in the United States among patients older than 45 years of age, and causes 5% of deaths worldwide. Moreover, COPD mortality is expected to increase by more than 30% over the next decade if current trends in tobacco smoking persist. Despite its increasing prevalence, COPD remains undiagnosed in many patients, thereby delaying important interventions that can prevent death and ameliorate symptoms and disability in those affected.

Working Definition of COPD

The Global Initiative for Obstructive Lung Disease (GOLD) Guidelines define COPD as a “preventable and treatable disease with some cardiopulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles and gases.” Clinically, COPD encompasses the disorders of chronic bronchitis and emphysema, features of which may overlap with one another in individual patients. Chronic bronchitis is clinically defined as a cough productive of sputum most days of the month, at least 3 months of the year for two successive years without other explanations. In contrast, emphysema is anatomically defined by inflammation and abnormal enlargement of alveolar sacs, ducts, and walls distal to the terminal bronchioles of the small airways. Application of these histopathologic guidelines is summarized in Chap. 20.

Epidemiology of COPD

A meta-analysis of multiple trials and studies that was conducted in 2004 estimated the worldwide prevalence of COPD to be approximately 7.6%. In the United States, where there are up to 24 million individuals with active or previous smoking histories, the estimated prevalence in adults aged 25-75 years is 6.9% for mild COPD (defined as FEV₁/FVC <70% and FEV₁ ≥80% predicted), and 6.6% for moderate COPD (FEV₁/FVC <70% and FEV₁ <80% predicted). These prevalences were established by the National Health and Nutrition Examination Survey III (NHANES-III). Furthermore, the Global Burden of Disease Study has projected that COPD will become the fifth leading cause of disability-adjusted life years lost by the year 2020.

Major Risk Factors for Development of COPD

The risk factors for COPD include both host and environmental factors (Table 22.1). With respect to host factors, alpha₁ proteinase inhibitor (α₁-PI) deficiency is the most well studied genetic predisposition to COPD. Inherited α₁-PI deficiency has a prevalence of approximately 1% in COPD populations, although this may underestimate its true incidence. Patients with α₁-PI deficiency may develop panacinar emphysema at relatively young ages (in the third to fourth decades of life), particularly in conjunction with exposure to tobacco smoke that greatly amplifies the likelihood of lung damage. The α₁-PI is a glycoprotein that inhibits the activities of proteolytic enzymes, especially neutrophil elastase. The normal homozygous PiMM phenotype is associated with a circulating [α₁-PI] of 20.0-53.0 μM, whereas the abnormal homozygous PiZZ phenotype is associated with severely deficient levels that are <15% of normal (ie, 2.5-7.0 μM). Other proteases, like the serine proteinases, matrix metalloproteinases, and cysteine proteinases, may also be involved in the pathophysiology of COPD. Specifically, it appears that an imbalance of proteinases and antiproteinases in the lungs of patients who are concomitantly exposed to environmental risk factors, such as tobacco smoke, predisposes those individuals to the development of emphysema.

Patients with COPD show more rapid declines in lung function over time when they have co-existing asthma and increased airway reactivity along with elevated circulating [IgE]. By one estimate, nonsmoking asthmatics were found to have a faster rate of decline in the FEV₁ (38-50 mL/year) than in non-asthmatics (22-35 mL/year). In the Lung Heart Health Study, methacholine reactivity during specialized pulmonary function testing (Chap. 16) was found to be an important predictor of progression of airway obstruction in continuing smokers with early COPD. Concerning gender, females are more than twice as likely to be diagnosed with chronic bronchitis as males, although for unclear reasons. Singly or in combination, factors that impair lung growth such as adverse gestational events, low birth weight, and childhood exposures, may reduce a person’s maximal attained lung function. This in turn may predispose to COPD.

Exposure to tobacco smoke is unquestionably the most important predisposing factor for COPD, accounting for 80%-90% of COPD mortality. Smokers have more respiratory symptoms, faster declines in lung function, and higher death rates due to COPD. Environmental tobacco exposure (passive/second-hand tobacco smoke exposure) has also been shown to increase the prevalence of: respiratory symptoms; bronchial hyperresponsiveness as determined from the physical finding of bronchospasm or from positive responses on methacholine challenge testing; and COPD itself. Other environmental risk factors for COPD include: occupational exposure to dust and chemicals; outdoor and indoor air pollution, notably smoke from home cooking and heating fuels; recurrent bronchopulmonary infections; and low socioeconomic status.

Making the Diagnosis of COPD

COPD is suspected in a patient who presents with cough, sputum production, and/or exertional dyspnea plus a history of exposure to risk factors, particularly cigarette smoke. Although COPD and asthma can coexist, careful evaluation of specific clinical features can help distinguish the predominant condition in each patient (Table 22.2).