Chronic obstructive pulmonary disease (chronic bronchitis and emphysema)

I. What every physician needs to know.

Chronic obstructive pulmonary disease (COPD), characterized by emphysema or chronic bronchitis, is a progressive, inflammatory disease that results in airflow limitation with some combination of small airway obstruction and lung destruction. COPD is the fourth leading cause of death in the United States. Symptoms include progressive dyspnea, cough and sputum production, with cough and sputum production as the most common early indicators.

COPD is characterized by chronic inflammation in all parts of the lung (including parenchyma, proximal and distal airways and vasculature). Inflammation is amplified by exposure to cigarette smoke, and repeated exacerbations result in progression of structural lung changes as well as a decline in lung function. Risk factors for COPD include alpha-1 antitrypsin deficiency, tobacco smoke (direct or environmental), indoor and outdoor pollutants, or occupational exposures (such as dust, vapors, irritants, or fumes).

II. Diagnostic Confirmation: Are you sure your patient has chronic obstructive pulmonary disease?

Diagnosis and classification of severity in COPD is made by spirometry. COPD is classified into 4 stages:

Stage I

Mild COPD (forced expiratory ratio (FEV) 1/forced vital capacity (FVC) less than 0.70, FEV1 greater than or equal to 80% predicted)
Patients may be asymptomatic and unaware of their abnormal lung function.

Stage II

Moderate COPD (FEV1/FVC less than 0.70, FEV1 less than 80% but greater than or equal to 50% predicted)
Patients may have dyspnea on exertion as well as some component of sputum production or chronic cough.

Stage III

Severe COPD (FEV1/FVC less than 0.70, FEV1 less than 50% but greater than or equal to 30% predicted)
Many patients will not present with symptoms until this stage, which is characterized by increased dyspnea, decreased exercise capacity and fatigue.

Stage IV

Very severe COPD (FEV1/FVC less than 0.70, FEV1 less than 30% predicted OR less than 50% predicted PLUS chronic respiratory failure).
Chronic respiratory failure is defined as an arterial oxygen tension (PaO₂) less than 60 on room air (with or without an arterial carbon dioxide tension (PaCO₂) greater than 50). Patients in this stage have severe impairment of quality of life and their exacerbations may be life threatening.

Additional testing is not required but full pulmonary function testing, with measurement of lung volumes and diffusing capacity, may support the diagnosis. Pulse oximetry and arterial blood glass measurement are used to determine whether a patient is a candidate for long-term oxygen therapy. Chest radiographs may show hyper-lucency and flattened diaphragms.

For anyone with evidence of COPD prior to the age of 45 and of Caucasian descent (or a family history of alpha-1 antitrypsin deficiency), a serum alpha-1 antitrypsin level should be measured.

A. History Part I: Pattern Recognition:

The diagnosis of COPD should be considered in anyone over the age of 40 with at least one of the following indicators: dyspnea that is persistent, progressive and worse with exercise, chronic cough (more than 4 weeks) or chronic sputum production. Chronic cough and sputum production are often the first symptoms to be noticed by the patient and are especially concerning for COPD in a patient with a history of exposure to tobacco smoke or occupational dusts or chemicals.

B. History Part 2: Prevalence:

Individuals with a chronic smoking history or a family history of alpha-1 antitrypsin deficiency are at highest risk for developing COPD. Other risk factors include exposure to second-hand smoke, home cooking or heating fuels, or occupational exposures to dusts or fumes. COPD rarely presents before age 35. Although COPD may have been historically thought of as a disease of men, the prevalence is now equal in men and women (likely reflecting increased smoking habits of women over the last 40 years).

C. History Part 3: Competing diagnoses that can mimic chronic obstructive pulmonary disease

The differential diagnosis for COPD includes asthma, heart failure, bronchiectasis, cystic fibrosis, bronchiolitis, upper airway obstruction (e.g. tumors or vocal cord dysfunction), interstitial lung disease, or pulmonary hypertension. COPD is distinguished from these diseases in that COPD presents during mid-life (often in someone with a long history of tobacco smoking), is slowly progressive, demonstrates dyspnea on exertion and shows largely irreversible airway obstruction on spirometry.

D. Physical Examination Findings.

The physical examination may be normal early in the disease course. As the disease progresses, patients often develop decreased breath sounds (likelihood ratio [LR] =10.2 for breath sound score less than or equal to 9), hyperresonance (LR=5.1), prolonged expiratory phase (LR=4.1 for forced expiratory time greater than or equal to 9 seconds), early inspiratory crackles (LR=14.6), or expiratory wheezing.

For patients with end-stage COPD, the physical exam may demonstrate increased anterior-posterior chest wall diameter, pursed lip breathing or use of accessory muscles of respiration.

E. What diagnostic tests should be performed?

As stated above, the diagnosis of COPD is made by spirometry. An exacerbation of COPD is a clinical diagnosis, characterized by the following major criteria: worsening dyspnea, an increase in sputum volume or an increase in sputum purulence.

Additional criteria that may be present during a COPD exacerbation include increased wheezing and cough, a fever with no apparent cause, an upper respiratory infection in the past 5 days, or an increase in respiratory rate or heart rate 20% above baseline. A mild exacerbation is defined as one major criterion and one additional criterion. A moderate exacerbation is two major criteria and a severe exacerbation is all three major criteria.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

No laboratory studies are needed to make a diagnosis of COPD. For patients with COPD diagnosed before age 45, the clinician should strongly consider sending a serum alpha-1 antitrypsin level.

For acute COPD exacerbations, patients should receive pulse oximetry monitoring and an arterial blood gas to evaluate for respiratory failure. Furthermore, it may be recommended to check a complete blood count and chemistry panel to evaluate for comorbid or complicating illnesses (such as anemia, electrolyte disturbances, hyperglycemia, or renal failure). If there is a concern for myocardial ischemia, a troponin level should also be obtained.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Imaging is a supplemental diagnostic test for COPD but generally includes a chest radiograph to evaluate for flattened diaphragms or hyperlucency. During a COPD exacerbation, a chest radiograph may be useful in excluding an alternative diagnosis of dyspnea (such as pneumonia or heart failure) or evaluating for complications of COPD (such as a pneumothorax).

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

None

III. Default Management.

A. Immediate management.

Immediate management of a COPD exacerbation includes obtaining a pulse oximetry reading and arterial blood gas to evaluate for respiratory failure. Additionally an electrocardiogram (EKG) should be obtained to identify any arrhythmias or ischemia that may be complicating the COPD exacerbation.

Initial treatment is focused on oxygen therapy to keep the patient’s oxygen saturation greater than 88% as well as providing short acting inhaled beta-2 agonists (albuterol). If the patient experiences an inadequate response to albuterol, inhaled anticholinergics should be added.

Oral steroids are useful in shortening recovery time and improving hypoxemia and FEV1. Prednisone 40 mg daily (or equivalent intravenous dose if unable to tolerate oral medications) for 5 days is sufficient for suppressing the inflammatory response, and higher doses of steroids are associated with increased side effects.

For patients with moderate to severe exacerbations (characterized by increased sputum volume or purulence in addition to dyspnea), antibiotics that cover common respiratory pathogens (Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis) should be initiated.

For patients presenting with respiratory acidosis (arterial blood gas (ABG) less than 7.35 and/or PaCO₂ greater than 45) or respiratory rate greater than 25 breaths per minute, non-invasive positive pressure ventilation is recommended. Non-invasive ventilation has been shown to improve respiratory acidosis, decrease respiratory rate, improve breathlessness, and shorten the hospital stay. Contraindications to non-invasive ventilation include respiratory arrest, cardiovascular instability, vomiting or aspiration risk, or mental status changes.

B. Physical Examination Tips to Guide Management.

For patients admitted with a COPD exacerbation, their pulmonary status (respiratory rate and work of breathing) as well as their neurologic status (mental status and level of alertness) should be monitored closely. With a response to therapy, patients should have resolving tachypnea and hypoxemia (back to near baseline oxygenation), decreased accessory muscle use, decreased tachycardia, improved air movement on lung auscultation, with a decrease in wheezing and decrease in length of the expiratory phase.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

No laboratory tests are needed to monitor response to treatment, although patients should have pulse oximetry measured every 4 hours to ensure adequate oxygenation. For patients requiring non-invasive ventilation, continuous pulse oximetry and telemetry monitoring is required. Serial blood gas monitoring should be used to help assess response to non-invasive ventilation.

D. Long-term management.

All patients with COPD who smoke should be urged to quit and referred to a smoking cessation program. All COPD patients benefit from an exercise program (pulmonary rehabilitation) and should receive the pneumococcal vaccine every 5 years and the influenza vaccine yearly.

Bronchodilators are the hallmark of therapy, and regular treatment with long-acting bronchodilators is more effective than short acting bronchodilators. Options for long-acting bronchodilators include tiotropium or aclidinium as an anticholinergic, or salmeterol, formoterol or aformoterol as a beta-2 agonist.

For patients with stage III or IV disease, inhaled corticosteroids should be added. For patients with stage IV disease, long-term oxygen therapy (more than 15 hours per day) should be added and has been shown to reduce mortality.

E. Common Pitfalls and Side-Effects of Management.

For patients with acute on chronic respiratory failure, care should be given to avoid overcorrecting hypoxemia. If hypoxemia is corrected too aggressively, the patient may develop worsening hypercapnea. Although correcting hypoxia does decrease minute ventilation slightly (by decreasing respiratory rate), suppression of the respiratory drive is not the major contributing factor to hypercapnea. Hypercapnea after oxygen administration is predominantly due to the ventilation-perfusion mismatch that occurs with the loss of hypoxic pulmonary vasoconstriction. Therefore, to decrease the likelihood of severe hypercapnea, a safe target oxygen saturation for patients with severe COPD and acute-on-chronic respiratory failure is between 88-92% (PaO2 of 60-70).

Prolonged treatment with systemic steroids should be avoided for the chronic treatment of COPD. During an acute exacerbation, steroids need to be given. Data has shown a course of 5 will be as effective as a course of 14 days for most people. Courses longer than 2 weeks have been associated with increased side effects. Similarly, for acute exacerbations, moderate-dose oral steroids (prednisone 30-60 mg daily) have been associated with lower cost, decreased length of stay and fewer side effects than intravenous steroids.

Pulmonary rehabilitation should be offered to all patients with moderate or severe COPD. Pulmonary rehabilitation following a COPD exacerbation has been shown to reduce future hospital admissions and mortality. The admission for an acute COPD exacerbation may be an optimal time to encourage a patient to attend pulmonary rehabilitation and for the physician to assist with the referral.

Treatment of acute exacerbations

For treatment of acute COPD exacerbations, albuterol 2.5 mg/3mL inhaled via nebulizer should be given every 2-4 hours as needed. For inadequate response, add ipratropium 500mcg inhaled via nebulizer every 4 hours as needed. Once improvement is noted, the patient can be transitioned to these medications via metered-dose inhaler with spacer.

Additionally the patient should be started on prednisone 40 mg daily for 5 days, and for moderate or severe exacerbations, antibiotics should be added for a period of 3-7 days. Intravenous steroids for acute COPD are not necessary in most instances. In a study by Lindenauer, use of oral steroids did not result in increased treatment failures compared to intravenous steroids, but oral steroids did decrease cost and length of stay. Commonly used antibiotics include trimethoprim/sulfamethoxazole, augmentin, macrolides (azithromycin), or fluoroquinolones (moxifloxacin, levofloxacin).

Care should be taken when prescribing fluoroquinolones to elderly patients (>60 years old) who are concomitantly taking steroids because of the uncommon, but increased risk of tendon rupture. For chronic management of COPD, common inhaled regimens to prevent exacerbations include either tiotropium 18 mcg daily or combination fluticasone 230 mcg/salmeterol 42 mcg daily, or budesonide 320 mcg/formoterol 10 mcg daily. For patients with severe COPD who meet certain criteria, lung-volume reduction surgery has been shown to improve a patient’s exercise capacity, dyspnea and quality of life but does NOT improve overall survival.