What is the best treatment approach for a patient experiencing a chronic obstructive pulmonary disease (COPD) exacerbation?

COPD Exacerbation Management

Immediate Bronchodilator Therapy

Initiate combination short-acting β2-agonist (salbutamol 2.5-5 mg) plus short-acting anticholinergic (ipratropium 0.25-0.5 mg) via nebulizer or metered-dose inhaler with spacer every 4-6 hours during the acute phase. 1, 2

• This combination provides superior bronchodilation lasting 4-6 hours compared to either agent alone 1, 2
• Nebulizers are preferred for sicker hospitalized patients who cannot coordinate the 20+ inhalations required with metered-dose inhalers 2
• Continue regular dosing for 24-48 hours until clinical improvement occurs 2
• Avoid methylxanthines (theophylline/aminophylline) entirely—they increase side effects without added benefit 2, 3

Systemic Corticosteroid Protocol

Administer prednisone 40 mg orally once daily for exactly 5 days starting immediately. 1, 2

• This 5-day regimen is equally effective as 14-day courses but reduces cumulative steroid exposure by over 50% 1, 2
• Oral administration is equally effective to intravenous and should be the default route unless the patient cannot tolerate oral intake 2
• Corticosteroids improve lung function, oxygenation, shorten recovery time, reduce treatment failure by over 50%, and prevent hospitalization for subsequent exacerbations within 30 days 1, 2
• Do not continue corticosteroids beyond 5-7 days after the acute episode unless there is a separate indication 2

Antibiotic Therapy Criteria

Prescribe antibiotics for 5-7 days when the patient has increased sputum purulence PLUS either increased dyspnea OR increased sputum volume (at least 2 of 3 cardinal symptoms). 1, 2

• First-line antibiotics include amoxicillin, amoxicillin/clavulanic acid, or tetracycline derivatives (doxycycline) 1, 2
• Alternative treatments include newer cephalosporins, macrolides (azithromycin), or quinolone antibiotics based on local bacterial resistance patterns 1, 2
• The most common organisms are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis 2
• Antibiotics reduce short-term mortality by 77%, treatment failure by 53%, and sputum purulence by 44% 2

Severity Assessment and Hospitalization Criteria

Hospitalize patients with any of the following: marked increase in dyspnea intensity, inability to eat or sleep due to symptoms, worsening hypoxemia or hypercapnia, changes in mental status, inability to care for oneself, uncertain diagnosis, inadequate home support, or failure to respond to initial outpatient management. 1, 2

• Mild exacerbations can be managed outpatient with short-acting bronchodilators only 1, 2
• Moderate exacerbations require short-acting bronchodilators plus antibiotics and/or oral corticosteroids, typically managed outpatient 1, 2
• Severe exacerbations require hospitalization or emergency department evaluation, particularly with acute respiratory failure 1, 2

Oxygen Therapy for Hospitalized Patients

Target oxygen saturation of 88-92% (or PaO2 ≥60 mmHg) using controlled oxygen delivery to avoid CO2 retention. 1, 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 1
• Obtain arterial blood gas measurement within 1 hour of initiating oxygen therapy to assess for worsening hypercapnia or acidosis 2
• Higher oxygen concentrations can worsen hypercapnic respiratory failure and increase mortality 2

Noninvasive Ventilation (NIV)

Initiate NIV immediately as first-line therapy for patients with acute hypercapnic respiratory failure, persistent hypoxemia despite oxygen, or severe dyspnea with respiratory muscle fatigue. 1, 2

• NIV improves gas exchange, reduces work of breathing, decreases intubation rates by approximately 65%, shortens hospitalization duration, and improves survival 1, 2
• Confused patients and those with large volumes of secretions are less likely to respond well to NIV 2
• Consider invasive mechanical ventilation if NIV fails, particularly in patients with a first episode of respiratory failure, demonstrable remedial cause, or acceptable baseline quality of life 2

Maintenance Therapy During and After Exacerbation

Continue existing triple therapy (LAMA/LABA/ICS) unchanged during the acute exacerbation—do not step down from triple therapy during or immediately after an exacerbation. 1, 2

• ICS withdrawal increases the risk of recurrent moderate-severe exacerbations, particularly in patients with eosinophils ≥300 cells/μL 2
• Initiate or optimize long-acting bronchodilator therapy (LAMA, LABA, or combinations) as soon as possible before hospital discharge 1, 2
• For patients with ≥2 moderate-to-severe exacerbations per year despite optimal triple therapy, consider adding long-term macrolide therapy (azithromycin 250-500 mg three times weekly) 2

Discharge Planning and Prevention

Schedule pulmonary rehabilitation within 3 weeks after discharge to reduce hospital readmissions and improve quality of life. 1, 2

• Do not initiate pulmonary rehabilitation during hospitalization, as this increases mortality 2
• Provide intensive smoking cessation counseling with nicotine replacement therapy and behavioral intervention at every visit for current smokers 2
• Review inhaler technique at every visit to ensure proper use and adherence 2
• At 8 weeks after an exacerbation, 20% of patients have not recovered to their pre-exacerbation state, highlighting the importance of follow-up care 2

Additional Supportive Measures for Hospitalized Patients

• Obtain chest radiograph on all hospitalized patients to exclude alternative diagnoses (pneumonia, pneumothorax, pulmonary edema), as chest X-ray changes management in 7-21% of cases 2
• Perform ECG if resting heart rate <60/min or >110/min, or if cardiac symptoms are present 2
• Administer prophylactic subcutaneous heparin for venous thromboembolism prevention in patients with acute-on-chronic respiratory failure 2
• Use diuretics only if there is peripheral edema and raised jugular venous pressure 2
• Avoid chest physiotherapy in acute exacerbations—there is no evidence of benefit 2

Common Pitfalls to Avoid

• Never use theophylline in acute exacerbations due to increased side effects without added benefit 2, 3
• Never delay NIV in patients with acute hypercapnic respiratory failure 2
• Never continue systemic corticosteroids beyond 5-7 days for a single exacerbation 2
• Never step down from triple therapy during or immediately after an exacerbation 2
• Never initiate pulmonary rehabilitation during hospitalization 2