9-06: Chronic Obstructive Pulmonary Disease

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines COPD as a common, preventable, and treatable disease state characterized by persistent respiratory symptoms and airflow limitation due to airway and alveolar abnormalities usually caused by significant exposure to noxious particles or gases. The term “COPD” has evolved from an umbrella term for chronic bronchitis and emphysema to one that refers to a clinical syndrome of chronic respiratory symptoms, structural pulmonary abnormalities (airways or alveoli), and impaired lung function arising from multiple causes that result in airflow limitation that is not fully reversible. Symptoms include cough, dyspnea, and sputum production. COPD is a major cause of chronic morbidity and is the third leading cause of death worldwide.

Cigarette smoking is by far the most important cause of COPD in North America and Western Europe. The majority of smokers suffer an accelerated decline in lung function that is dose- and duration-dependent. One major study of active smokers reported yearly decreases in FEV₁ of 66 mL per year in men and 54 mL per year in women compared to 30 mL per year in men and 22 mL per year in women who sustained smoking cessation. Fifteen percent of smokers develop progressively disabling symptoms in their 40s and 50s. Approximately two-thirds of patients seen for COPD have significant exposure to tobacco smoke. The remaining one-third may have a combination of exposures to environmental tobacco smoke, occupational dusts and chemicals, and indoor air pollution from biomass fuel used for cooking and heating in poorly ventilated buildings. Outdoor air pollution, airway infection, environmental factors, and allergy have also been implicated, along with hereditary factors (most notably, deficiency of alpha-1-antiprotease [alpha-1-antitrypsin]). Atopy and bronchoconstriction in response to nonspecific airway stimuli may be important risk factors. There is evidence that lung exposures to pollution and allergens early in life can lead to poor lung growth in childhood and expiratory airflow limitation, resulting in lower than predicted spirometric values in midlife.

A. Symptoms and Signs

Patients with COPD characteristically present in the fifth or sixth decade of life complaining of excessive cough, sputum production, and shortness of breath. Symptoms have often been present for 10 years or more, yet if diagnosed early, smoking cessation can reduce the decline in lung function. Dyspnea is noted initially only on heavy exertion, but as the condition progresses it occurs with mild activity. In severe disease, dyspnea occurs at rest. As the disease progresses, two symptom patterns tend to emerge, historically referred to as “pink puffers” and “blue bloaters” (Table 9–6). Most COPD patients have features of both disorders, and their clinical course and severity may involve other factors, such as central control of ventilation and concomitant sleep-disordered breathing.

A hallmark of COPD is the acute exacerbation of symptoms beyond normal day-to-day variation, often including increased dyspnea, an increased frequency or severity of cough, and increased sputum volume or change in sputum character. These exacerbations are commonly precipitated by infection (more often viral than bacterial) or environmental factors. Pneumonia, pulmonary hypertension, cor pulmonale, and chronic respiratory failure characterize the late stage of COPD.

B. Laboratory Findings

Spirometry provides objective information about pulmonary function and assesses the response to therapy. Pulmonary function tests early in the course of COPD may reveal only abnormal closing volume and reduced mid-expiratory flow rates. Reductions in FEV₁ and in the ratio of FEV₁ to vital capacity (FEV₁% or FEV₁/FVC ratio) establish the presence of airflow obstruction. In severe disease, the FVC is markedly reduced. Lung volume measurements reveal an increase in residual volume (RV) and in total lung capacity (TLC), and an elevation of the RV/TLC ratio, indicative of air trapping, particularly common in patients with emphysema (eFigure 9–3). In the setting of airflow obstruction, a reduction in the single breath diffusing capacity (DL_CO) predicts pulmonary emphysema. A severely reduced DL_CO predicts exertional oxyhemoglobin desaturation and is associated with coexisting pulmonary hypertension. A 6-minute walking distance of less than 350 m is associated with increased mortality.

ABG measurement characteristically shows no abnormalities early in COPD other than an increased A–a–DO₂. Indeed, ABG measurement is unnecessary unless (1) hypoxemia or hypercapnia is suspected, (2) the FEV₁ is less than 40% of predicted, or (3) there are clinical signs of right heart failure. Hypoxemia occurs in advanced disease, particularly when chronic bronchitis predominates. Compensated respiratory acidosis occurs in patients with chronic respiratory failure, particularly in chronic bronchitis, with worsening of acidemia during acute exacerbations.

Examination of the sputum may reveal Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. However, positive sputum cultures are poorly correlated with acute exacerbations, and research techniques demonstrate evidence of preceding viral infection in most patients with exacerbations. The ECG may show sinus tachycardia and, in advanced disease, chronic pulmonary hypertension may produce electrocardiographic abnormalities typical of cor pulmonale. Supraventricular arrhythmias (multifocal atrial tachycardia, atrial flutter, and atrial fibrillation) and ventricular irritability also occur.

C. Imaging

Radiographs of patients with chronic bronchitis typically show only nonspecific peribronchial and perivascular markings. Plain radiographs are insensitive for the diagnosis of emphysema; they show hyperinflation with flattening of the diaphragm or peripheral arterial deficiency in about half of cases (eFigure 9–4) (eFigure 9–5). CT of the chest identifies and can quantify the emphysema phenotype associated with loss of tissue. Chest CT also detects airway narrowing and wall thickening characteristic of the bronchitic phenotype. In advanced disease, pulmonary hypertension may be suggested by enlargement of central pulmonary arteries on chest radiographs or chest CTs, and Doppler echocardiography provides an estimate of pulmonary artery pressure.

Clinical, imaging, and laboratory findings should enable the clinician to distinguish COPD from other obstructive pulmonary disorders, such as asthma, bronchiectasis, cystic fibrosis, bronchopulmonary mycosis, and central airflow obstruction. Asthma is characterized by complete or near-complete reversibility of airflow obstruction. Bronchiectasis is distinguished from COPD by recurrent pneumonia and hemoptysis, digital clubbing, and characteristic imaging abnormalities. Cystic fibrosis occurs in children, adolescents, and young adults and has characteristic imaging as well as endocrine and hepatic abnormalities. Bronchopulmonary mycosis is characterized by eosinophilia; elevated levels of immunoglobulin E; and episodic worsening marked by fever, malaise, productive cough, and radiographic infiltrates. Mechanical obstruction of the central airways can be distinguished from COPD by flow-volume loops.

Acute bronchitis, pneumonia, pulmonary thromboembolism, atrial dysrhythmias (such as atrial fibrillation, atrial flutter, and multifocal atrial tachycardia), and concomitant left ventricular failure may worsen otherwise stable COPD. Pulmonary hypertension, cor pulmonale, and chronic respiratory failure are common in advanced COPD. Spontaneous pneumothorax occurs in a small fraction of patients with emphysema. Hemoptysis may result from chronic bronchitis or may signal bronchogenic carcinoma.

COPD is largely preventable through elimination of long-term exposure to tobacco smoke, products of combustion of biomass fuels, and other inhaled toxins. Smokers with early evidence of airflow limitation can significantly alter the course of their disease by smoking cessation. Influenza vaccination reduces the frequency and severity of influenza-like illness as well as the number of COPD exacerbations. Pneumococcal vaccination appears to reduce both the frequency of community-acquired pneumonia and the number of COPD exacerbations.

The treatment of COPD is guided by the severity of symptoms or the presence of an exacerbation of stable symptoms. Standards for the management of patients with stable COPD and COPD exacerbations from the American Thoracic Society and GOLD, a joint expert committee of the National Heart, Lung, and Blood Institute and the World Health Organization, are incorporated in the recommendations below. There are three commonly used ways to identify high-risk COPD patients who may require more intense treatment: (1) FEV₁ less than 50% (GOLD III/IV), (2) more than two exacerbations within the previous year, and (3) one or more hospitalizations for COPD exacerbation in the previous year.

A. Ambulatory Patients

1. Smoking cessation

The single most important intervention in smokers with COPD is to encourage smoking cessation (see Chapter 1). Simply telling a patient to quit succeeds 5% of the time. Behavioral approaches, ranging from clinician advice to intensive group programs, may improve cessation rates. Pharmacologic therapy includes bupropion, nicotine replacement (transdermal patch, gum, lozenge, inhaler, or nasal spray), and varenicline (a partial agonist of nicotinic acetylcholine receptors). Combined pharmacotherapies (two forms of nicotine replacement, or nicotine replacement and bupropion), with or without behavioral approaches, have been recommended. Varenicline is effective but use has been limited by concerns about neuropsychiatric side effects. Electronic cigarettes are marketed as an aid for tobacco smoking cessation. One 2019 RCT showed electronic cigarettes doubled abstinence from tobacco smoking at 1 year, but 80% of participants randomized to electronic cigarettes were still using those devices at 1 year. Most pulmonologists do not recommend electronic cigarettes as a tobacco cessation aid, based on safety concerns (they are not regulated and contain a variety of chemicals) and limited clinical trial data.

2. Oxygen therapy

Supplemental oxygen for patients with resting hypoxemia (PaO₂ < 56 mm Hg) is the only therapy with evidence of improvement in the natural history of COPD. Proved benefits of home oxygen therapy in hypoxemic patients include longer survival, reduced hospitalizations, and better quality of life. Survival in hypoxemic patients with COPD treated with supplemental oxygen therapy is directly proportionate to the number of hours per day oxygen is administered: in COPD hypoxemic patients treated with continuous oxygen for 24 hours daily, the survival after 36 months is about 65%—significantly better than the survival rate of about 45% in those treated with only nocturnal oxygen. Oxygen by nasal prongs must be given for at least 15 hours a day unless therapy is specifically intended only for exercise or sleep. However, several studies of supplemental oxygen therapy showed no survival benefit in COPD patients with borderline low-normal resting oxygen levels (PaO₂ between 56 mm Hg and 69 mm Hg). In a study of patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to first hospitalization or death than no long-term supplemental oxygen, nor did it provide sustained benefit in any other measured outcomes. Requirements for US Medicare coverage for a patient’s home use of oxygen and oxygen equipment are listed in Table 9–7. ABG analysis is preferred over oximetry to guide initial oxygen therapy. Hypoxemic patients with pulmonary hypertension, chronic cor pulmonale, erythrocytosis, impaired cognitive function, exercise intolerance, nocturnal restlessness, or morning headache are particularly likely to benefit from home oxygen therapy.

Home oxygen may be supplied by liquid oxygen systems, compressed gas cylinders, or oxygen concentrators. Most patients benefit from having both stationary and portable systems. For most patients, a flow rate of 1–3 L/min achieves a PaO₂ greater than 55 mm Hg. Reservoir nasal cannulas or “pendants” and demand (pulse) oxygen delivery systems are available to conserve oxygen.

3. Inhaled bronchodilators

Bronchodilators do not alter the inexorable decline in lung function that is a hallmark of COPD, but they improve symptoms, exercise tolerance, FEV₁, and overall health status. Aggressiveness of bronchodilator therapy should be matched to the severity of the patient’s disease. In patients who experience no symptomatic improvement, bronchodilators should be discontinued.

The most commonly prescribed short-acting bronchodilators are the SAMAs, ipratropium bromide, and the SABAs (eg, albuterol, metaproterenol), delivered by MDI or as an inhalation solution by nebulizer. Some clinicians prefer ipratropium as a first-line agent because of its longer duration of action and absence of sympathomimetic side effects. Some studies have suggested that ipratropium achieves superior bronchodilation in COPD patients. Typical doses are 2–4 puffs (36–72 mcg) every 6 hours. Other clinicians prefer SABAs because they are less expensive and have a more rapid onset of action, commonly leading to greater patient satisfaction. At maximal doses, beta-2-agonists have bronchodilator action equivalent to that of ipratropium but may cause tachycardia, tremor, or hypokalemia. There does not appear to be any advantage of scheduled use of SABAs compared with as-needed administration. There has been no consistent difference in efficacy demonstrated between SABAs and SAMAs. Using the SABAs and the SAMAs at submaximal doses leads to improved bronchodilation compared with either agent alone but does not improve dyspnea.

LAMAs (eg, tiotropium, aclidinium, umeclidinium) and LABAs (eg, formoterol, salmeterol, indacaterol, arformoterol, vilanterol) appear to achieve bronchodilation that is equivalent or superior to what is experienced with ipratropium, in addition to similar improvements in health status. Although more expensive than short-acting agents, long-acting bronchodilators may have superior clinical efficacy in persons with advanced disease. One RCT of long-term administration of tiotropium added to standard therapy reported fewer exacerbations or hospitalizations, and improved dyspnea scores, in the tiotropium group. Tiotropium had no effect on long-term decline in lung function, however. Another RCT comparing the effects of tiotropium with those of salmeterol-fluticasone over 2 years reported no difference in the risk of COPD exacerbation. The incidence of pneumonia was higher in the salmeterol-fluticasone group, yet dyspnea scores were lower and there was a mortality benefit compared with tiotropium. The combination of tiotropium and formoterol (LAMA/LABA) has been shown to improve FEV₁ and FVC more than the inhaled corticosteroid/LABA combination salmeterol and fluticasone in patients with a baseline FEV₁ of less than 55% predicted. The initial drug of choice for patients with mild disease and no exacerbations is a LAMA. If the patient has more severe dyspnea and airflow obstruction, LAMA/LABA can be initiated.

The symptomatic benefits of long-acting bronchodilators are firmly established. Increased exacerbations and mortality reported in some asthmatic patients treated with salmeterol have not been observed in COPD patients, and several studies report a trend toward lower mortality in patients treated with salmeterol alone, compared with placebo. In addition, a 4-year tiotropium trial reported fewer cardiovascular events in the intervention group. Subsequent meta-analyses that include the 4-year tiotropium trial did not find an increase in cardiovascular events in treated patients. Most practitioners believe that the documented benefits of anticholinergic therapy outweigh any potential risks.

4. Corticosteroids

Multiple large clinical trials have reported a reduction in the frequency of COPD exacerbations and an increase in self-reported functional status in COPD patients treated with inhaled corticosteroids. These same trials demonstrate no effect of inhaled corticosteroids on mortality or the characteristic decline in lung function experienced by COPD patients. Thus, inhaled corticosteroids alone should not be considered first-line therapy in stable COPD patients.

Three large clinical trials of combination therapy with an inhaled corticosteroid added to a LABA demonstrated a reduced frequency of exacerbations and modest improvements in lung function. The benefits of inhaled corticosteroids must be weighed against the 1.57-fold increased relative risk of bacterial pneumonia, however. Withdrawal of inhaled corticosteroids should be considered when patients have been stable for 2 years.

Apart from acute exacerbations, COPD is not generally responsive to oral corticosteroid therapy. Given the risks of adverse side effects, oral corticosteroids are not recommended for long-term treatment of COPD.

5. Theophylline

Oral theophylline is a fourth-line agent for treating COPD patients who do not achieve adequate symptom control with inhaled anticholinergic, beta-2-agonist, and corticosteroid therapies. Theophylline improves dyspnea ratings, exercise performance, and pulmonary function in many patients with stable COPD. Its benefits result from bronchodilation; anti-inflammatory properties; and extrapulmonary effects on diaphragm strength, myocardial contractility, and kidney function. Theophylline toxicity is a significant concern due to the medication’s narrow therapeutic window, and long-term administration requires careful monitoring of serum levels (eTable 9–2). GOLD guidelines recommend theophylline only as a last resort if other bronchodilators are unavailable or unaffordable.

6. Antibiotics

Antibiotics are commonly prescribed to outpatients with COPD for the following indications: (1) to treat an acute exacerbation, (2) to treat acute bronchitis, and (3) to prevent acute exacerbations of chronic bronchitis (prophylactic antibiotics). In patients with COPD, antibiotics appear to improve outcomes slightly in all three situations. Patients with a COPD exacerbation associated with increased sputum purulence accompanied by dyspnea or an increase in the quantity of sputum are thought to benefit the most from antibiotic therapy. The choice of antibiotic depends on local bacterial resistance patterns and individual risk of Pseudomonas aeruginosa infection (history of Pseudomonas isolation, FEV₁ less than 50% of predicted, recent hospitalization [2 or more days in the past 3 months], more than three courses of antibiotics within the past year, use of systemic corticosteroids). Oral antibiotic options include doxycycline (100 mg every 12 hours), trimethoprim-sulfamethoxazole (160/800 mg every 12 hours), a cephalosporin (eg, cefpodoxime 200 mg every 12 hours or cefprozil 500 mg every 12 hours), a macrolide (eg, azithromycin 500 mg followed by 250 mg daily for 5 days), a fluoroquinolone (eg, ciprofloxacin 500 mg every 12 hours), and amoxicillin-clavulanate (875/125 mg every 12 hours). Suggested duration of therapy is 3–5 days and depends on response to therapy. There are few controlled trials of antibiotics in severe COPD exacerbations, but prompt administration is appropriate, particularly in persons with risk factors for poor outcomes (age older than 65 years, FEV₁ less than 50% of predicted, three or more exacerbations in the past year, antibiotic therapy within the past 3 months, comorbid conditions, such as cardiac disease). In COPD patients subject to frequent exacerbations despite optimal medical therapy, azithromycin (daily or three times weekly) and moxifloxacin (a 5-day course 1 week in 8 over 48 weeks) were modestly effective in clinical trials at reducing the frequency of exacerbations; monitoring for hearing loss and QT prolongation is essential.

7. Pulmonary rehabilitation

Graded aerobic physical exercise programs (eg, walking 20 minutes three times weekly or bicycling) are helpful to prevent deterioration of physical condition and to improve patients’ ability to carry out daily activities. Training of inspiratory muscles by inspiring against progressively larger resistive loads reduces dyspnea and improves exercise tolerance, health status, and respiratory muscle strength in some but not all patients. Pursed-lip breathing to slow the rate of breathing and abdominal breathing exercises to relieve fatigue of accessory muscles of respiration may reduce dyspnea in some patients. Many patients undergo these exercise and educational interventions in a structured rehabilitation program. Pulmonary rehabilitation has been shown in multiple studies to improve exercise capacity, decrease hospitalizations, and enhance quality of life. Referral to a comprehensive rehabilitation program is recommended in patients who have severe dyspnea, reduced quality of life, or frequent hospitalizations despite optimal medical therapy.

8. Phosphodiesterase 4 inhibitor

Roflumilast has been shown to reduce exacerbation frequency in patients who have moderate or severe (FEV₁ less than 50% of predicted) COPD and chronic bronchitis, with frequent exacerbations and are taking LABA/inhaled corticosteroid with or without a LAMA.

9. Other measures

In patients with chronic bronchitis, increased mobilization of secretions may be accomplished through adequate systemic hydration, effective cough training methods, or the use of a handheld flutter device and postural drainage, sometimes with chest percussion or vibration. Postural drainage and chest percussion should be used only in selected patients with excessive amounts of retained secretions that cannot be cleared by coughing and other methods; these measures are of no benefit in pure emphysema. Expectorant-mucolytic therapy has generally been regarded as unhelpful in patients with chronic bronchitis. Cough suppressants and sedatives should be avoided. Morphine can reduce chronic dyspnea in patients with very severe COPD.

Human alpha-1-antitrypsin is available for replacement therapy in emphysema due to congenital deficiency (PiZZ or null genotype) of alpha-1-antiprotease (alpha-1-antitrypsin). Patients over 18 years of age with airflow obstruction by spirometry and serum levels less than 11 mmol/L (∼50 mg/dL) are potential candidates for replacement therapy. Alpha-1-antitrypsin is administered intravenously in a dose of 60 mg/kg body weight once weekly. There is no evidence that replacement therapy is beneficial to heterozygotes (eg, PiMZ) with low-normal serum levels, although such patients may be at slightly increased risk for emphysema, especially in the setting of tobacco smoke exposure.

Severe dyspnea in spite of optimal medical management may warrant a clinical trial of an opioid (eg, morphine 5–10 mg orally every 3–4 hours, oxycodone 5–10 mg orally every 4–6 hours, sustained-release morphine 10 mg orally once daily). Sedative-hypnotic drugs (eg, diazepam, 5 mg three times daily) marginally improve intractable dyspnea but cause significant drowsiness; they may benefit very anxious patients. Transnasal positive-pressure ventilation at home to rest the respiratory muscles is an approach to improve respiratory muscle function and reduce dyspnea in patients with severe COPD.

See Chapter 37 for a discussion of air travel in patients with lung disease.

B. Hospitalized Patients

Management of the hospitalized patient with an acute exacerbation of COPD includes (1) supplemental oxygen (titrated to maintain SaO₂ between 90% and 94% or PaO₂ between 60 mm Hg and 70 mm Hg); (2) inhaled ipratropium bromide (500 mcg by nebulizer, or 36 mcg by MDI with spacer, every 4 hours as needed) plus beta-2-agonists (eg, albuterol 2.5 mg diluted with saline to a total of 3 mL by nebulizer, or MDI, 90 mcg per puff, four to eight puffs via spacer, every 1–4 hours as needed); (3) corticosteroids (prednisone 0.5 mg/kg/day orally for 7–10 days is usually sufficient, even 5 days may be adequate); (4) broad-spectrum antibiotics; and (5) in selected cases, chest physiotherapy.

For patients without risk factors for Pseudomonas, management options include a fluoroquinolone (eg, levofloxacin 750 mg orally or intravenously per day, or moxifloxacin 400 mg orally or intravenously every 24 hours) or a third-generation cephalosporin (eg, ceftriaxone 1 g intravenously per day, or cefotaxime 1 g intravenously every 8 hours).

For patients with risk factors for Pseudomonas, therapeutic options include piperacillin-tazobactam (4.5 g intravenously every 6 hours), ceftazidime (1 g intravenously every 8 hours), cefepime (1 g intravenously every 12 hours), or levofloxacin (750 mg orally or intravenously per day for 3–7 days).

Oxygen therapy should not be withheld for fear of worsening respiratory acidemia; hypoxemia is more detrimental than hypercapnia. Cor pulmonale usually responds to measures that reduce pulmonary artery pressure, such as supplemental oxygen and correction of acidemia; bed rest, salt restriction, and diuretics may add some benefit. Cardiac dysrhythmias, particularly multifocal atrial tachycardia, usually respond to aggressive treatment of COPD itself. Atrial fibrillation and flutter may require DC cardioversion after initiation of the above therapy. Theophylline should not be initiated in the acute setting, but patients taking theophylline prior to acute hospitalization should have their theophylline serum levels measured and maintained in the therapeutic range. If progressive respiratory failure ensues, tracheal intubation and mechanical ventilation are necessary. In clinical trials of COPD patients with hypercapnic acute respiratory failure, noninvasive positive-pressure ventilation (NIPPV) delivered via face mask reduced the need for intubation and shortened lengths of stay in the intensive care unit (ICU). Other studies have suggested a lower risk of nosocomial infections and less use of antibiotics in COPD patients treated with NIPPV.

C. Procedures for COPD

1. Lung transplantation

Experience with both single and bilateral sequential lung transplantation for severe COPD is extensive. Requirements for lung transplantation are severe lung disease, limited activities of daily living, exhaustion of medical therapy, ambulatory status, potential for pulmonary rehabilitation, limited life expectancy without transplantation, adequate function of other organ systems, and a good social support system. Two-year survival rate after lung transplantation for COPD is 75%. Complications include acute rejection, opportunistic infection, and obliterative bronchiolitis. Substantial improvements in pulmonary function and exercise performance have been noted after transplantation.

2. Lung volume reduction surgery

Lung volume reduction surgery (LVRS), or reduction pneumoplasty, is a surgical approach to relieve dyspnea and improve exercise tolerance in patients with advanced diffuse emphysema and lung hyperinflation. Bilateral resection of 20–30% of lung volume in selected patients results in modest improvements in pulmonary function, exercise performance, and dyspnea. The duration of improvement as well as any mortality benefit remains uncertain. Prolonged air leaks occur in up to 50% of patients postoperatively. Mortality rates in centers with the largest experience with LVRS range from 4% to 10%.

The National Emphysema Treatment Trial compared LVRS with medical treatment in a randomized, multicenter clinical trial of 1218 patients with severe emphysema. Overall, surgery improved exercise capacity but not mortality when compared with medical therapy. The persistence of this benefit remains to be defined. Subgroup analysis suggested that patients with upper lobe–predominant emphysema and low exercise capacity might have improved survival, while other groups suffered excess mortality when randomized to surgery.

3. Bullectomy

Bullectomy is an older surgical procedure for palliation of dyspnea in patients with severe bullous emphysema. Bullectomy is most commonly pursued when a single bulla occupies at least 30–50% of the hemithorax. In this procedure, the surgeon removes a large emphysematous bulla that demonstrates no ventilation or perfusion on lung scanning and compresses adjacent lung with preserved function. Bullectomy can be performed with a CO₂ laser via thoracoscopy.

4. Endobronchial valves

In some patients with advanced emphysema and very severe air trapping but without collateral flow between lobes, one-way valves may allow for flow out of but not into hyperinflated areas of lung, and thereby reduce hyperinflation. The US Food and Drug Administration recently approved one such device based on a trial showing significant improvements in FEV₁, 6-minute-walk distance, and respiratory symptoms in the treatment group compared to controls. The inclusion criteria for this trial included FEV₁ between 15% and 45% of predicted, total lung capacity greater than 100% of predicted, and residual volume greater than 175% of predicted. The degree to which this therapy will enter widespread use remains to be seen.

The outlook for patients with clinically significant COPD is poor. The degree of pulmonary dysfunction at the time the patient is first seen is an important predictor of survival: median survival of patients with FEV₁ = 1 L or less is about 4 years. A multidimensional index (the BODE index), which includes body mass index, airway obstruction (FEV₁), dyspnea (modified Medical Research Council dyspnea score), and exercise capacity, is a tool that predicts death and hospitalization better than FEV₁ alone. Comprehensive care programs, cessation of smoking, and supplemental oxygen may reduce the rate of decline of pulmonary function, but therapy with bronchodilators and other approaches probably have little, if any, impact on the natural course of COPD.

Dyspnea at the end of life can be extremely uncomfortable and distressing to the patient and family. As patients near the end of life, meticulous attention to palliative care is essential to effectively manage dyspnea (see Chapter 5).

• COPD onset occurs before the age of 40.

• Frequent exacerbations (two or more a year) despite optimal treatment.

• Severe or rapidly progressive COPD.

• Symptoms disproportionate to the severity of airflow obstruction.

• Need for long-term oxygen therapy.

• Onset of comorbid illnesses (eg, bronchiectasis, heart failure, or lung cancer).

• Severe symptoms or acute worsening that fails to respond to outpatient management.

• Acute or worsening hypoxemia, hypercapnia, peripheral edema, or change in mental status.

• Inadequate home care, or inability to sleep or maintain nutrition/hydration due to symptoms.

• The presence of high-risk comorbid conditions.