What is the treatment for Chronic Obstructive Pulmonary Disease (COPD) exacerbation?

Treatment for COPD Exacerbation

For acute COPD exacerbations, initiate treatment with short-acting inhaled β2-agonists (with or without short-acting anticholinergics), systemic corticosteroids (40 mg prednisone daily for 5 days), and antibiotics when indicated by increased sputum purulence plus either increased dyspnea or sputum volume. 1, 2

Severity Classification and Treatment Setting

COPD exacerbations should be classified to guide treatment intensity 1:

• Mild exacerbations: Treated with short-acting bronchodilators only in the outpatient setting 1, 3
• Moderate exacerbations: Require short-acting bronchodilators plus antibiotics and/or oral corticosteroids, typically managed outpatient 1, 3
• Severe exacerbations: Require hospitalization or emergency department evaluation; may be associated with acute respiratory failure 1, 3

More than 80% of exacerbations can be managed on an outpatient basis 2, 3

Bronchodilator Therapy

Short-acting inhaled β2-agonists (SABAs), with or without short-acting anticholinergics, are the first-line bronchodilators for acute treatment. 1, 2, 3

• For moderate exacerbations, either a beta-agonist or anticholinergic should be given via nebulizer 2
• For severe exacerbations, both SABA and short-acting anticholinergics should be administered together 2
• Either metered-dose inhalers with spacers or nebulizers can be used effectively, though nebulizers may be easier for sicker patients 2, 3
• Methylxanthines (theophylline) are not recommended due to their side effect profile 1, 2, 3, 4

Systemic Corticosteroid Therapy

Systemic corticosteroids improve lung function, oxygenation, shorten recovery time, and reduce hospitalization duration. 1, 2

Dosing and Duration

• The recommended dose is 40 mg prednisone daily for 5 days 2, 5
• Oral prednisolone is equally effective to intravenous administration for most patients 2, 3
• Duration should not exceed 5-7 days 3, 6, 5

The REDUCE trial (n=314) demonstrated that 5-day treatment with 40 mg prednisone daily was noninferior to 14-day treatment for preventing reexacerbation within 6 months (HR 0.95; 90% CI 0.70-1.29), while significantly reducing glucocorticoid exposure (379 mg vs 793 mg cumulative dose). 5 This high-quality evidence supports shorter treatment courses. 6, 5

Important Caveats

• Corticosteroids may be less efficacious in patients with lower blood eosinophil levels 2, 3
• Treatment increases the risk of adverse effects, particularly hyperglycemia (OR 2.79; 95% CI 1.86-4.19) 7
• Overall, one extra adverse effect occurs for every six people treated 7

Antibiotic Therapy

Antibiotics should be given when there is increased sputum purulence plus either increased dyspnea or increased sputum volume. 2, 3

• Antibiotics reduce the risk of short-term mortality by 77%, treatment failure by 53%, and sputum purulence by 44% 2
• The recommended duration is 5-7 days 2, 3
• Initial empirical treatment typically includes aminopenicillin with clavulanic acid, a macrolide (such as azithromycin), or a tetracycline 3, 8
• Antibiotic choice should be based on local bacterial resistance patterns 3

Oxygen Therapy

• The aim is to achieve SpO2 ≥90% without causing respiratory acidosis 2
• In patients with known COPD aged 50 years or older, initial FiO2 should not exceed 28% via Venturi mask or 2 L/min via nasal cannulae until arterial blood gases are known 2

Respiratory Support for Severe Exacerbations

Noninvasive ventilation (NIV) should be the first mode of ventilation for patients with acute respiratory failure who have no absolute contraindication. 1, 2, 3

• NIV improves gas exchange, reduces work of breathing, decreases need for intubation, shortens hospitalization duration, and improves survival 2, 3

Post-Exacerbation Management

Maintenance therapy with long-acting bronchodilators should be initiated as soon as possible before hospital discharge. 1, 2, 3

• Consider LAMA monotherapy, ICS/LABA combination therapy, or LAMA/LABA combination therapy 2, 3
• Combination therapy has shown greater efficacy in preventing exacerbations than monotherapy in patients with moderate to severe COPD 2, 3
• At 8 weeks after an exacerbation, 20% of patients have not recovered to their pre-exacerbation state, highlighting the importance of follow-up 2, 3
• Appropriate measures for exacerbation prevention should be initiated, including smoking cessation counseling and medication review 3

Common Pitfalls

• Do not use ipratropium bromide as a single agent for acute exacerbations, as drugs with faster onset of action are preferable as initial therapy 4
• Ensure proper differentiation from other conditions: acute coronary syndrome, worsening congestive heart failure, pulmonary embolism, and pneumonia can mimic COPD exacerbations 1, 2
• Avoid prolonged corticosteroid courses beyond 5-7 days, as they increase adverse effects without additional benefit 3, 6, 5
• ICS therapy may increase the risk of pneumonia in COPD patients, which should be carefully considered when assessing risk/benefit ratios 3