What is the treatment for an adult patient with chronic obstructive pulmonary disease (COPD) experiencing an acute exacerbation, possibly with a history of smoking or exposure to lung irritants and comorbidities such as cardiovascular disease or diabetes?

Treatment of Acute COPD Exacerbation

For an adult patient experiencing an acute COPD exacerbation, immediately initiate short-acting bronchodilators (beta-agonists with or without anticholinergics), oral prednisone 30-40 mg daily for exactly 5 days, and antibiotics if the patient has increased sputum purulence plus either increased dyspnea or increased sputum volume. 1

Initial Assessment and Severity Classification

Classify the exacerbation severity to determine treatment setting 2, 1:

• Mild exacerbations: Treat with short-acting bronchodilators only, manageable at home 2, 1
• Moderate exacerbations: Require bronchodilators plus antibiotics and/or oral corticosteroids, often manageable outpatient 2, 1
• Severe exacerbations: Require hospitalization or emergency department evaluation, particularly with acute respiratory failure, marked symptom intensity, severe underlying COPD, new physical signs, significant comorbidities, or inability to care for self at home 2, 1

More than 80% of exacerbations can be managed on an outpatient basis 1. However, hospitalization should be considered for patients requiring nebulization (indicating inability to achieve adequate bronchodilation with standard inhalers), persistent rhonchi after initial treatment, or need for close monitoring to detect respiratory failure 1.

Immediate Pharmacological Management

Bronchodilator Therapy

Administer short-acting beta-2 agonists (such as albuterol 2.5-5 mg) combined with short-acting anticholinergics (such as ipratropium 0.25-0.5 mg) via nebulizer or metered-dose inhaler with spacer. 2, 1 This combination provides superior bronchodilation lasting 4-6 hours compared to either agent alone 1. Repeat dosing every 4-6 hours during the acute phase (typically 24-48 hours) until clinical improvement occurs 1.

Nebulizers are preferred over metered-dose inhalers in sicker hospitalized patients because they are easier to use and don't require coordination of 20+ inhalations needed to match nebulizer efficacy 1. However, either metered-dose inhalers (with or without spacer) or nebulizers can be used effectively 1.

Avoid methylxanthines (theophylline) due to increased side effect profiles without added benefit. 2, 1

Systemic Corticosteroid Protocol

Administer oral prednisone 30-40 mg once daily for exactly 5 days. 2, 1, 3 This duration is equally effective as 14-day courses but reduces cumulative steroid exposure by over 50% 1, 3. Oral administration is equally effective to intravenous and should be the default route unless the patient cannot tolerate oral intake 2, 1, 3.

Systemic corticosteroids improve lung function (FEV1), oxygenation, shorten recovery time and hospitalization duration, and reduce treatment failure by over 50% 2, 1, 3. They prevent hospitalization for subsequent exacerbations within the first 30 days following the initial exacerbation 1, 3.

Critical limitation: Do not continue corticosteroids beyond 5-7 days after the acute episode unless there is a separate indication for long-term treatment 2, 1, 3. Extending therapy beyond 7 days increases adverse effects (hyperglycemia, weight gain, insomnia) without providing additional clinical benefit 1, 3. Systemic corticosteroids should NOT be given for the sole purpose of preventing exacerbations beyond the first 30 days 3.

For patients who cannot take oral medications: Use IV hydrocortisone 100 mg or IV methylprednisolone 2, 1, 3. However, IV corticosteroids may increase adverse effects without clear benefit over oral administration and are associated with longer hospital stays and higher costs 1, 3.

Blood eosinophil count ≥2% predicts better response to corticosteroids (treatment failure rates of only 11% versus 66% in placebo), but current guidelines recommend treating all COPD exacerbations requiring emergent care regardless of eosinophil levels 3.

Antibiotic Therapy

Prescribe antibiotics for 5-7 days if the patient has at least two of the following cardinal symptoms: increased dyspnea, increased sputum volume, or increased sputum purulence. 2, 1 Antibiotics reduce the risk of short-term mortality by 77%, treatment failure by 53%, and sputum purulence by 44% 1.

First-line antibiotic choices (based on local bacterial resistance patterns) 1:

• Amoxicillin
• Amoxicillin/clavulanic acid
• Doxycycline or other tetracycline derivatives
• Macrolides (azithromycin)

Alternative treatments for patients with risk factors for resistant organisms 1:

• Newer cephalosporins
• Quinolone antibiotics (fluoroquinolones)

The most common organisms causing COPD exacerbations are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and viruses 1, 4.

Hospital Management for Severe Exacerbations

Oxygen Therapy and Monitoring

Target oxygen saturation of 88-92% using controlled oxygen delivery. 1 Higher oxygen concentrations can worsen hypercapnic respiratory failure and increase mortality in COPD patients 1.

Obtain arterial blood gas measurement within 60 minutes of initiating oxygen therapy to assess for worsening hypercapnia, acidosis, or adequate oxygenation 1. Perform pulse oximetry immediately upon arrival and obtain arterial blood gases if SpO2 <90% or if respiratory acidosis is suspected 1.

Noninvasive Ventilation (NIV)

For patients with acute hypercapnic respiratory failure, persistent hypoxemia despite oxygen, or severe dyspnea with respiratory muscle fatigue, initiate noninvasive ventilation immediately as first-line therapy. 2, 1 NIV improves gas exchange, reduces work of breathing, decreases intubation rates by reducing need for intubation, shortens hospitalization duration, and improves survival 2, 1.

Confused patients and those with large volumes of secretions are less likely to respond well to NIV 1. 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 1.

Additional Supportive Measures

• Diuretics: Use only if there is peripheral edema and raised jugular venous pressure 1
• Prophylactic subcutaneous heparin: Recommended for patients with acute-on-chronic respiratory failure 1
• Avoid chest physiotherapy: No evidence of benefit in acute exacerbations of COPD 1

Diagnostic Testing

Obtain chest radiograph on all hospitalized patients to exclude alternative diagnoses (pneumonia, pneumothorax, pulmonary edema, pulmonary embolus, lung cancer), as chest X-ray changes management in 7-21% of cases 2, 1. Perform ECG if resting heart rate <60/min or >110/min, or if cardiac symptoms are present 1.

Discharge Planning and Post-Exacerbation Management

Maintenance Therapy Optimization

Initiate or optimize long-acting bronchodilator therapy before hospital discharge. 2, 1 Maintenance therapy with long-acting bronchodilators (LAMA, LABA, or combinations) should be started as soon as possible 2, 1.

Do not step down from triple therapy (LAMA/LABA/ICS) during or immediately after exacerbation, as ICS withdrawal increases the risk of recurrent moderate-severe exacerbations, particularly in patients with eosinophils ≥300 cells/μL 1.

For patients with ≥2 moderate-to-severe exacerbations per year despite optimal triple therapy, consider adding 1:

• Long-term macrolide therapy (azithromycin 250-500 mg three times weekly) - requires consideration of potential QT prolongation, hearing loss, and bacterial resistance
• Roflumilast (PDE-4 inhibitor) for patients with chronic bronchitic phenotype (chronic cough and sputum production)
• N-acetylcysteine for patients with chronic bronchitic phenotype

Pulmonary Rehabilitation

Schedule pulmonary rehabilitation within 3 weeks after discharge to reduce hospital readmissions and improve quality of life 2, 1. Do not initiate pulmonary rehabilitation during hospitalization, as this increases mortality; wait until post-discharge 1.

Follow-Up and Prevention

Schedule follow-up within 3-7 days to assess response. 1 The follow-up visit represents an opportunity to help the patient plan for future exacerbation prevention 2, 1. At 8 weeks after an exacerbation, 20% of patients have not recovered to their pre-exacerbation state, highlighting the importance of follow-up care 1.

Provide intensive smoking cessation counseling with nicotine replacement therapy and behavioral intervention at every visit for current smokers 1. Review inhaler technique at every visit to ensure proper use and adherence to treatment 1.

Ensure vaccinations: Influenza and pneumococcal vaccines should be given 4.

Common Pitfalls to Avoid

• Do not default to IV corticosteroids for all hospitalized patients, as this increases costs and adverse effects without improving mortality, readmission rates, or treatment failure 1, 3
• Do not extend corticosteroid therapy beyond 5-7 days for a single exacerbation, as this increases adverse effects without additional benefit 1, 3
• Do not use theophylline in acute exacerbations due to its side effect profile 2, 1
• Do not delay NIV in patients with acute hypercapnic respiratory failure 1
• Do not use systemic corticosteroids long-term for exacerbation prevention, as risks (infection, osteoporosis, adrenal suppression) far outweigh any benefits 1, 3
• Do not prescribe antibiotics indiscriminately - only when at least two cardinal symptoms are present, with increased sputum purulence being particularly important 1