Definition and Epidemiology

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by airflow limitation; it is usually progressive, not fully reversible, and associated with an abnormal inflammatory response of the lungs. The chronic airflow limitations of COPD are caused by a combination of both small airway disease and parenchymal destruction.¹ Chronic obstructive pulmonary disease is a term used to describe two related lung diseases: chronic bronchitis and emphysema.²

Chronic bronchitis is defined clinically as a chronic, persistent cough or sputum production for 3 consecutive months each year for 2 consecutive years, with periodic acute exacerbations during which the symptoms worsen.³ The pathologic features include inflammation of the cells lining the bronchial wall, hyperplasia of the mucous glands, and narrowing of the small airways.⁴

Emphysema is the permanent and abnormal enlargement of any part of the air spaces distal to the terminal bronchioles. Emphysema also involves destruction of the alveolar walls without fibrosis.⁴

COPD does not include other obstructive lung diseases such as asthma, even though asthma shares the same pathophysiologic common denominator as chronic bronchitis and emphysema, which is a slowing of the expiratory flow rate.² Asthma involves inflammation of the small airways. Although it is generally reversible, asthma can result in progressive airflow obstruction that over time becomes less and less reversible and resembles the obstruction seen with chronic bronchitis and emphysema. Persons with COPD can have a mix of emphysema, chronic bronchitis, and asthma that ranges from a “pure” emphysematous picture to a mixture of all three.

COPD is the third leading cause of death in the United States and the fourth leading cause of death worldwide.¹ Centers for Disease Control and Prevention statistics show that COPD has advanced from being the fourth to being the third leading cause of death between 1999 and 2010.⁵ According to Social Security disability statistics, it is second only to coronary heart disease in causing disability. This shows a marked increase in the numbers of COPD cases worldwide since 1990, when it was ranked sixth. In the United States, where mortality from multiple chronic conditions declined from 1970 to 2002, COPD mortality rates increased.¹ Approximately 12.7 million adults in the United States have been diagnosed with COPD. However, almost 24 million U.S. adults have evidence of impaired lung function, indicating that the true prevalence of COPD is likely to be greatly underdiagnosed.⁶

COPD is predominantly a smoker’s disease that clusters in families and worsens with age. Approximately 80% to 90% of COPD deaths are caused by smoking.⁶ A hereditary pattern caused by α₁-antitrypsin deficiency contributes to the pure emphysematous form of this disease.

The risks for COPD include genetic, behavioral, socioeconomic, and environmental factors (Box 106-1). Cigarette smoke and an occupation that involves regular exposure to a dusty environment are the two major external factors. Because smoking cessation slows the decline in the expiratory airflow, it is clear that smoking is a powerful factor in determining outcome. When the disease is advanced, however, degeneration of lung function will probably continue even with smoking cessation. COPD is more common among individuals who are poor or undereducated. Cigarette smoking is also more common in these groups, but indigent populations still have worse lung function even with adjustment for smoking status. Other contributing factors include crowded living conditions with exposure to frequent viral infections, poorly ventilated homes, inadequate nutrition, exposure to passive cigarette smoke, and suboptimum care for childhood respiratory infections. Air pollution from the burning of wood and other biomass fuels has also been identified as a risk factor for COPD.¹

Morbidity and mortality rates from COPD are higher in Caucasians than in African Americans or any other racial group in the United States.⁷ Mortality has always been higher in men than in women. However, data from the past three decades have demonstrated a gender shift in the number of smoking-related COPD cases being diagnosed each year.⁶ Some studies have suggested that women are more susceptible to the effects of smoking then men¹; 2014 marked the eleventh consecutive year in which more women than men died as a result of COPD.⁶

Physician consultation is recommended for the initial diagnosis and management of patients with a significant change in condition or a failure to improve with prescribed therapies.

Pathophysiology

The cause of chronic bronchitis is not well understood, but chronic infection and airway hyperreactivity play important roles. The inflammatory process continues unabated even after withdrawal of prolonged exposure to bronchial irritants such as smoke, dust, and fumes. Airway edema, airway wall thickening, excess production of mucus, and loss of ciliary function result. Airflow is obstructed during both inspiration and expiration. Widespread bronchial narrowing with mucous plugging produces hypoxemia because of the mismatching of ventilation and perfusion. Hypercapnia results from the lack of ventilation. Chronic hypoxia and hypercapnia increase pulmonary arterial resistance and may lead to the development of pulmonary hypertension and, eventually, cor pulmonale. A sudden worsening of symptoms in severe chronic bronchitis can precipitate acute right-sided heart failure. Chronic bronchitis causes much less parenchymal damage than emphysema does; therefore, diffusing capacity, lung volumes, and compliance of lung tissue are not greatly altered.⁴

Enlargement of air spaces in emphysema is the result of alveolar wall destruction. This process is not completely understood but probably results from increased numbers of activated neutrophils that produce elastases, enzymes that destroy the elastin elements in the alveolar walls. Neutrophil-derived elastase is one of a group of destructive proteases contained in alveolar tissue. Usually, a small amount of neutrophil elastase is inactivated by antielastases (also known as antiproteases), which are found in the serum and lung lining layer. The prime antielastase, which is present in the largest quantities, is α₁-antitrypsin.

Even though they account for less than 3% of cases, patients with a hereditary deficiency of α₁-antitrypsin have less inhibition of elastase and a much higher risk for development of emphysema.⁴ The primary role of α₁-antitrypsin is to inhibit the function of several proteases, most notably human neutrophil elastase. Human neutrophil elastase degrades the protein elastin, which is key to the elastic recoil mechanism necessary for the lung’s expiratory function. The lack of α₁-antitrypsin can lead to panacinar emphysema. Because the alveoli have lost their recoil mechanism, the driving force during respiration decreases and causes a chronic persistent airflow obstruction. In addition to inhibiting proteases, α₁-antitrypsin inhibits the function of lymphocytes, macrophages, and neutrophils.⁸ Patients with a hereditary deficiency of α₁-antitrypsin have less inhibition of elastase and a much higher risk for development of emphysema.

Cigarette smoking also increases elastase activity by causing an influx of elastase-rich neutrophils into the alveoli and by causing the oxidative inactivation of antitrypsin. These processes result in a 30-fold increase in the risk for COPD.

Regardless of the mechanism, the end result of COPD is the destruction of alveolar architecture and the capillary bed lying within the alveolar wall. Initially, the reduction in size of the vascular bed parallels the fall in alveolar surface area. Ventilation still roughly matches perfusion, and significant hypoxemia does not ensue. As the disease progresses, the elastic recoil of the airways is lost, and the poorly supported noncartilaginous airways collapse during expiration. Expiratory flow rates fall as a result, causing decreased airflow. Because this airflow obstruction is not uniform throughout the lung, there is uneven distribution of ventilation and blood perfusion. This uneven distribution causes arterial hypoxemia (decreased PaO₂); decreased ventilation causes hypercapnia (increased PaCO₂).

Clinical Presentation

Diagnosis of COPD requires a thorough patient history, physical examination, and diagnostic testing. The most common presenting complaint is dyspnea on exertion. This symptom develops late in the course of this disease, when irreversible changes may have already occurred.

COPD must be considered as a diagnosis in every patient who smokes, even in the absence of respiratory symptoms. Discussing smoking habits at every visit is an important strategy in the prevention of irreversible disease. Documentation should include onset of smoking, the average number of packs per day, and whether the patient has made any successful cessation attempts. Information about other respiratory symptoms, such as cough, sputum production, and exertional dyspnea, should be elicited and quantified.

The important medical history includes any recurrent or prolonged respiratory tract infections that have required antibiotic treatment. A childhood history of frequent respiratory tract infections and bronchitis and any history of asthma, recurrent sinus infections, or nasal polyps should be documented because such conditions are common in patients with COPD.

The family history, including allergies, tuberculosis, cystic fibrosis, COPD, and other chronic lung conditions, should be elicited. A detailed occupational history with special attention to exposure to noxious inhalants such as fumes and mineral and biologic dust is essential.¹

Physical Examination

Early in the disease process, the physical examination findings are often normal. Even without the findings of advanced COPD, it is impossible to exclude the diagnosis in the person at risk. However, if COPD is suspected based on the history and examination, it can be confirmed physiologically with simple spirometry.¹ In the late stages of COPD, the general physical findings include those resulting from hyperinflation. Inspection of the skin may show tobacco stains on the fingers and, occasionally, clubbing of the fingernails (convex nail plates). Chest inspection reveals an increase in the anteroposterior diameter, an increase in the intercostal spaces, and, in severe cases, abnormal retraction of the interspaces during inspiration. With inspiration, there is diminished movement of the rib cage and increased movement of the abdominal wall. Abdominal and sternocleidomastoid muscles may be well developed but accompanied by diminished muscle mass in the thighs and legs. A forward-sitting posture with both hands on the knees to fix the shoulders, thereby permitting more effective use of the accessory cervical muscles, may be noted. Pursed-lip breathing with prolonged expirations is also characteristic of COPD.¹

There is increased resonance on chest percussion. The diaphragm seems low and moves poorly with deep inspiration and expiration. Diminished transmission of breath sounds on auscultation is the most reliable finding; this indicates chronic airflow limitation. Early inspiratory crackles are commonly found. Wheezing may be elicited with forced expiration, but it is a nonspecific symptom and is more characteristic of asthma.¹

Lung disease causes hypertrophy of the right ventricle of the heart, resulting in cor pulmonale. Therefore, chronic cor pulmonale may be present in the advanced stage of COPD. The physical examination may reveal neck vein distention, peripheral edema, and hepatomegaly from an elevated right atrial pressure. Pulmonary hypertension and distention of the right ventricle cause a pronounced cardiac impulse in the epigastrium.

Diagnostics

Early detection of COPD is important for decreasing the associated morbidity and mortality. Symptoms of COPD do not usually occur until a significant amount of lung damage has occurred. A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough, sputum production, and a history of exposure to risk factors for the disease, such as smoking or occupational exposures to dust and chemicals.¹ A simple office maneuver called forced expiratory time may help determine if further testing is needed. The patient is asked to take a deep breath in and then to breathe out as quickly and completely as possible with the mouth open. The practitioner auscultates the trachea with the diaphragm of the stethoscope and times the audible expiration. A forced expiratory time of 6 seconds or more suggests obstructive pulmonary disease.⁹ The diagnosis should be confirmed by spirometry. Spirometry is considered the gold standard of diagnosis and assessment of COPD because it is the most reproducible, standardized, and objective way of measuring airflow limitation. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), and the ratio of the two (FEV₁/FVC) are the primary spirometric measurements used for diagnosis. The presence of a postbronchodilator FEV₁/FVC of less than 0.70 and FEV₁ of less than 80% predicted confirms airflow limitation that is not fully reversible.¹ COPD is usually a progressive disease; the general patterns of symptom development are well established, and lung function usually worsens over time despite medical intervention (Box 106-2).

The concept of staging COPD based on FEV₁ alone is now thought to be inadequate. Newer research indicates the management of stable COPD should be based on a combination of factors including a symptomatic assessment, spirometric classification, and future risk of disease progression, with the focus on exacerbations.¹

The COPD Assessment Test (CAT) is a short but comprehensive eight-item measure of health status impairment in patients with COPD.¹ It has been validated and can be easily used in a routine practice setting. It is scored from 0 to 40, with scores greater then 10 indicating more severe symptoms.

There is a large body of accumulated data in patients classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry grading system. The data show an increased risk of exacerbations, hospitalization, and death with worsening airflow limitations. The assessment of exacerbation risk is seen as a risk of poor outcomes overall¹ (Box 106-3).

A posteroanterior and lateral chest x-ray study is rarely diagnostic in COPD unless significant bullous disease is present. However, x-ray examination is useful in detection of COPD complications, such as pneumonia, pulmonary hypertension, and pneumothorax, as well as in establishing the presence of comorbidities, such as cardiac failure. Radiographic changes in COPD include flattening of the diaphragm and blunting of the costophrenic angle on the posteroanterior view, enlargement of the retrosternal space on the lateral view, flattening or concavity of the diaphragmatic contour on the lateral view, and irregularity of lung field lucency.¹

Pulse oximetry to estimate oxygen saturation can be helpful, but blood gas measurements are necessary to assess and to manage patients during exacerbations and when oxygen therapy is indicated. Elevations of hematocrit and hemoglobin provide a measure of the severity of hypoxemia. Phlebotomy may become necessary if the elevation is severe. An electrocardiogram can indicate the severity of the lung disease and the presence of cor pulmonale. Significant findings include sinus tachycardia, multifocal atrial tachycardia, signs of right atrial enlargement (peaked P waves in leads II, III, and aVF), signs of right ventricular hypertrophy (a tall R wave in lead V₁ and a deep S wave in lead V₆), and right-axis deviation.⁸

Sputum is not routinely examined, but its inspection can help differentiate between a pulmonary infection and an exacerbation of reactive airways. The detection of neutrophils or eosinophils in the sputum will guide treatment between antibiotics and corticosteroids. Measurement of α₁-antitrypsin level is indicated in white patients who develop COPD before the age of 45 years or who have a strong family history of premature emphysema or α₁-antitrypsin deficiency.¹

Differential Diagnosis

Distinguishing COPD from other causes of chronic cough or dyspnea is important for initial diagnosis and in acute exacerbations. A chronic cough may be secondary to chronic sinusitis or chronic rhinitis from allergies or postinfectious states. Gastroesophageal reflux, neoplasms, tuberculosis, interstitial lung diseases, and heart diseases (e.g., mitral stenosis or those causing chronic pulmonary edema) may also cause chronic cough. Chronic cough may be a side effect of certain drugs, including angiotensin-converting enzyme inhibitors, beta blockers, and amiodarone.

Diseases that cause chronic dyspnea include COPD, chronic bronchitis, emphysema, cystic fibrosis, and asthma. Less common entities include diffuse interstitial lung disease, pulmonary vascular disease (including recurrent pulmonary emboli, pulmonary hypertension, and arteriovenous malformation), and malignant neoplasms (including bronchogenic carcinoma and pulmonary metastatic disease). Phrenic nerve dysfunction or neuromuscular diseases can cause respiratory muscle weakness. Chest wall abnormalities, especially kyphoscoliosis, will cause chronic dyspnea. There are also nonpulmonary causes of dyspnea, including anemia, obesity, ascites, metabolic acidosis, hyperthyroidism, congenital heart disease, and abnormal hemoglobinopathies.

Certain features may help distinguish COPD from some of the most common pulmonary diseases that share similar signs and symptoms. The onset of COPD is more likely to be in midlife, with a long history of smoking and slowly progressing symptoms.¹ The onset of asthma is usually earlier in life, with varying symptoms occurring during the night and early morning. The patient often has a family history of asthma and may also have allergies, rhinitis, or eczema. The airflow limitations associated with asthma are largely reversible. Features suggestive of congestive heart failure include fine basilar crackles on auscultation and volume restriction versus airflow limitation on pulmonary function tests. A dilated heart and pulmonary edema may be noted on chest radiography. Bronchiectasis is associated with large volumes of purulent sputum and is commonly associated with bacterial infection. Coarse crackles may be noted on auscultation, and bronchial dilation and bronchial wall thickening may be seen on chest radiography or computed tomography. Tuberculosis can occur at any age. Lung infiltrates are usually noted on chest radiography with microbiologic confirmation. This occurs most often when there is a high local prevalence of tuberculosis.¹