Chronic Obstructive Pulmonary Disease (COPD)

Essentials of Diagnosis

• History of cigarette smoking or other chronic inhalational exposure

• Chronic cough, dyspnea, and sputum production

• Rhonchi, decreased intensity of breath sounds, and prolonged expiration on physical examination

• Airflow limitation on pulmonary function testing

General Considerations

• 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

• Cigarette smoking is by far the most important cause of COPD in North America and Western Europe

• Other causes include exposures to

  • Environmental tobacco smoke

  • Occupational dusts and chemicals

  • 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

Symptoms and Signs

• Presentation

  • Usually at 40–50 years of age

  • Cough

  • Sputum production

  • Shortness of breath

• Dyspnea initially occurs only with heavy exertion, progressing to symptoms at rest in severe disease

• Exacerbation of symptoms beyond normal day-to-day variation, often including increased dyspnea, an increased frequency or severity of cough, increased sputum volume, or change in sputum character

• Infections (viral more commonly than bacterial) precede exacerbations in most patients

• Late-stage COPD characterized by

  • Hypoxemia

  • Pneumonia

  • Pulmonary hypertension

  • Cor pulmonale

  • Respiratory failure

• Clinical findings may be absent early

• Patients are often dichotomized as "pink puffers" or "blue bloaters" depending on whether emphysema or chronic bronchitis predominates (Table 9–6)

Differential Diagnosis

• Asthma

• Bronchiectasis, which features recurrent pneumonia and hemoptysis, with distinct radiographic findings

• Bronchopulmonary mycosis

• Central airflow obstruction

• Cystic fibrosis, which is usually first seen in children and young adults

Laboratory Tests

• Sputum examination may reveal

  • Streptococcus pneumoniae

  • Haemophilus influenzae

  • Moraxella catarrhalis

  • Cultures correlate poorly with exacerbations

• ECG shows sinus tachycardia, abnormalities consistent with cor pulmonale in severe disease, and/or supraventricular tachycardias and ventricular irritability

• Arterial blood gas values

  • Unnecessary unless hypoxemia or hypercapnia is suspected

  • May show only an increased A–a DO₂ in early disease

  • Hypoxemia in advanced disease

  • Compensated respiratory acidosis with worsening acidemia during exacerbations

• Single-breath diffusing capacity for carbon monoxide (DL_CO)

  • When severely reduced, it predicts pulmonary emphysema

  • Also predicts exertional oxyhemoglobin desaturation

  • Associated with coexisting pulmonary hypertension

  • A 6-minute walking distance of < 350 m is associated with increased mortality

• Spirometry

  • Objectively measures pulmonary function and assesses severity

  • Early changes are reductions in midexpiratory flow and abnormal closing volumes

  • FEV₁ and FEV₁/FVC are reduced later in disease

  • FVC is reduced in severe disease

  • Lung volume measurements show an increase in total lung capacity (TLC), residual volume (RV), and an elevation of RV/TLC indicating air trapping

• Alpha-1-antiprotease level in young patients with emphysema

Imaging Studies

• 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

• In advanced disease, radiographs that show enlarged central pulmonary arteries may indicate pulmonary hypertension

• Chest CT

  • Identifies and can quantify the emphysema phenotype associated with loss of tissue

  • Also detects airway narrowing and wall thickening characteristic of the bronchitic phenotype

• Doppler echocardiography provides a noninvasive estimate of pulmonary artery pressure

Medications

• Supplemental oxygen

  • Hypoxemic patients with pulmonary hypertension, chronic cor pulmonale, erythrocytosis, impaired cognitive function, exercise intolerance, nocturnal restlessness, or morning headache are likely to benefit from home oxygen therapy

  • Benefits of home oxygen therapy in patients with hypoxemia include longer survival, reduced hospitalizations, and better quality of life

  • Unless therapy is intended only for night-time or exercise use, 15 hours of nasal oxygen per day is required

  • For most patients, a flow rate of 1–3 L achieves a PaO₂ > 55 mm Hg

• Bronchodilators

  • Do not alter lung decline that is hallmark of disease

  • However, many patients experience improvement in symptoms, exercise tolerance, FEV₁, and overall health (Tables 9–2 and 9–3)

  • Ipratropium bromide (2–4 puffs via MDI every 6 hours) is first-line therapy because it is longer-acting and without sympathomimetic side effects

  • Short-acting beta-agonists (albuterol, metaproterenol) have a shorter onset of action and are less expensive

  • At maximal doses, bronchodilation with beta-agonists is equivalent to ipratropium, but with side effects of tremor, tachycardia, and hypokalemia

  • Ipratropium and beta-agonists together are more effective than either alone

  • Long-acting beta-agonists (formoterol, salmeterol, indacaterol, arformoterol, vilanterol) and antimuscarinic anticholinergics (tiotropium, aclidinium, umeclidinium) appear to achieve bronchodilation that is equivalent or superior to what is experienced with ipratropium in addition to similar improvements in health status

• Inhaled corticosteroids

  • Should not be considered first-line therapy in stable COPD patients

  • However, three large clinical trials of combination therapy with an inhaled corticosteroid and long-acting beta-agonist showed a reduced frequency of exacerbations and modest improvements in lung function

• Oral theophylline

  • Fourth-line agent for patients who do not achieve adequate symptom control with inhaled anticholinergic, beta-2-agonist, and corticosteroid therapies

  • GOLD guidelines recommend theophylline only as a last resort if other bronchodilators are unavailable or unaffordable

• Antibiotics improve outcomes slightly when used to treat acute exacerbations

  • Doxycycline (100 mg every 12 hours),

  • Trimethoprim-sulfamethoxazole (160/800 mg every 12 hours)

  • Cephalosporins (cefpodoxime 200 mg every 12 hours; cefprozil 500 mg every 12 hours)

  • Macrolides (azithromycin 500 mg followed by 250 mg daily for 5 days)

  • Fluoroquinolones (ciprofloxacin 500 mg every 12 hours)

  • Amoxicillin-clavulanate (875/125 mg every 12 hours)

• Azithromycin (daily or thrice 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 COPD exacerbations in persons optimally managed with medical therapy

• Opioids: severe dyspnea in spite of optimal management may warrant a 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 (diazepam 5 mg three times daily orally) may benefit very anxious patients with intractable dyspnea

• Management of the hospitalized patient with an acute exacerbation includes

  • Supplemental oxygen (titrated to maintain SaO₂ between 90% and 94% or PaO₂ between 60 mm Hg and 70 mm Hg)

  • 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)

  • Corticosteroids (prednisone 0.5 mg/kg/day orally for 7–10 days is usually sufficient, even 5 days may be adequate)

  • Broad-spectrum antibiotics

  • Chest physiotherapy (in select cases)

• 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)

  • 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)

  • Levofloxacin (750 mg orally or intravenously per day for 3–7 days)

Surgery

• Lung transplantation offers substantial improvement in pulmonary function and exercise performance; 2-year survival is 75%

• Lung volume reduction surgery in highly selected patients results in modest improvements in pulmonary function, exercise performance, and dyspnea; surgical mortality rates at experienced centers are 4–10%

• Bullectomy

  • Used for palliation of dyspnea in patients with severe bullous emphysema

  • Most commonly pursued when a single bulla occupies at least 30–50% of the hemithorax

Therapeutic Procedures

• Smoking cessation is the single most important goal

• Cough suppressants and sedatives should be avoided as routine measures

• Graded physical exercise programs

• Measure theophylline levels in hospitalized patients who have already been taking theophylline; it should not be started in the acute setting

• Noninvasive positive pressure ventilation

  • Reduces the need for intubation

  • Shortens ICU lengths of stay

  • May reduce the risk of health care–associated infection and antibiotic use

Complications

• Otherwise stable COPD may be made worse by

  • Acute bronchitis

  • Pneumonia

  • Pulmonary thromboembolism

  • Atrial dysrhythmias, such as atrial fibrillation, atrial flutter, and multifocal atrial tachycardia

  • Concomitant left ventricular failure

• Pulmonary hypertension, cor pulmonale, and chronic respiratory failure are common in advanced disease

• Spontaneous pneumothorax occurs in a small fraction of emphysematous patients

• Hemoptysis may result from chronic bronchitis or bronchogenic carcinoma

Prevention

• Largely preventable by eliminating chronic exposure to tobacco smoke, products of combustion of biomass fuels, and other inhaled toxins

• Vaccination against influenza and pneumococcal infection

Prognosis

• Median survival of patients with FEV₁ < 1 L is 4 years

• Degree of dysfunction at presentation is the most important predictor of survival

• A multidimensional index (the BODE index), which includes body mass index (BMI), airway obstruction (FEV₁), dyspnea (Medical Research Council dyspnea score), and exercise capacity, predicts death and hospitalization better than FEV₁ alone

When to Refer

• 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 (such as bronchiectasis, heart failure, or lung cancer)

When to Admit

• 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