What is the protocol for treating Chronic Obstructive Pulmonary Disease (COPD) and its exacerbations?

Protocol for COPD Treatment and Exacerbation Management

The management of COPD and its exacerbations should follow a stepwise approach with short-acting bronchodilators as initial treatment for exacerbations, systemic corticosteroids to reduce clinical failure, and antibiotics in appropriate cases, while maintenance therapy should include long-acting bronchodilators with additional therapies based on patient phenotype. 1

Classification of COPD Exacerbations

Exacerbations are classified by severity, which determines the treatment approach:

• Mild: Treated with short-acting bronchodilators only
• Moderate: Requires short-acting bronchodilators plus antibiotics and/or oral corticosteroids
• Severe: Requires hospitalization or emergency room visit, often associated with acute respiratory failure 1

Acute Exacerbation Management

Initial Pharmacological Treatment

1. Short-acting bronchodilators:

   • First-line treatment: Short-acting β2-agonists (e.g., salbutamol 2.5-5 mg) with or without short-acting anticholinergics (e.g., ipratropium bromide 0.25-0.5 mg)
   • Administration: Via nebulizer or inhaler with spacer 1

2. Systemic corticosteroids:

   • Dosage: Oral prednisone 30-40 mg daily for 5-7 days
   • Benefits: Reduces treatment failure and relapse within one month 1

3. Antibiotics:

   • Indicated when at least two of the following symptoms are present:
     • Increased breathlessness
     • Increased sputum volume
     • Development of purulent sputum
   • Selection based on severity:
     • Mild cases: Amoxicillin or tetracycline
     • Moderate to severe cases: Amoxicillin-clavulanate or ciprofloxacin 1

Oxygen Therapy and Ventilatory Support

1. Oxygen administration:

   • Target saturation: 88-92%
   • Initial approach: FiO₂ ≤28% via Venturi mask or ≤2 L/min via nasal cannulae
   • Monitoring: Arterial blood gases within 60 minutes if initially acidotic or hypercapnic 1

2. Non-invasive ventilation (NIV):

   • First option for patients with acute respiratory failure without contraindications
   • Consider when: pH <7.26, rising PaCO₂, or failure to respond to supportive treatment 1

Special Considerations

• Diuretics: Indicated if peripheral edema and raised jugular venous pressure are present
• Anticoagulants: Consider prophylactic subcutaneous heparin for patients with acute-on-chronic respiratory failure
• Medication adjustments:
  • Renal insufficiency: Avoid medications with significant renal elimination
  • Diabetes: Monitor blood glucose levels more frequently with corticosteroids
  • Beta-blockers: Be aware of potentially reduced response to beta-agonists 1

Maintenance Therapy for Stable COPD

1. Long-acting bronchodilators:

   • Initiate before hospital discharge
   • Long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) in combination are the mainstay of treatment 1, 2
   • LAMA/LABA combinations show improved FEV1 response compared to monotherapy 3

2. Add-on therapy based on patient phenotype:

   • For patients with frequent exacerbations despite LAMA/LABA:
     • With asthma-COPD overlap or high blood eosinophil counts: Add inhaled corticosteroids (ICS) 2, 4
     • With chronic bronchitis: Consider PDE-4 inhibitor (roflumilast) or high-dose mucolytic agents 4
     • With frequent bacterial exacerbations/bronchiectasis: Consider mucolytic agents or macrolide antibiotics 4

3. Prevention strategies:

   • Smoking cessation
   • Vaccination (influenza, pneumococcal)
   • Pulmonary rehabilitation
   • Early recognition and treatment of exacerbations 1

Follow-up and Monitoring

• Follow-up timing:

  • Mild exacerbations: Within 48 hours
  • Moderate exacerbations: Within 1-2 weeks after discharge 1

• Monitoring parameters:

  • Worsening symptoms
  • Decreasing oxygen saturation
  • Altered mental status
  • Inability to maintain oral intake 1

Common Pitfalls and Caveats

1. Differential diagnosis: Important to rule out alternative conditions that may mimic COPD exacerbations:

   • Pneumonia
   • Pneumothorax
   • Left ventricular failure/pulmonary edema
   • Pulmonary embolism
   • Lung cancer
   • Upper airway obstruction
   • Acute coronary syndrome 1

2. Treatment errors to avoid:

   • Delayed ventilatory support can increase mortality
   • Insufficient duration of therapy can lead to relapse
   • Overuse of inhaled corticosteroids in patients without appropriate indications 1, 2

3. Risk factors for frequent exacerbations:

   • History of previous exacerbations
   • Increased ratio of pulmonary artery to aorta cross-sectional dimension
   • Greater percentage of emphysema or airway wall thickness on CT imaging
   • Worse lung function
   • Lower exercise capacity
   • Chronic bronchitis
   • Continued smoking 1

Evidence on Treatment Efficacy

• Tiotropium 5 mcg significantly reduces the number of COPD exacerbations compared to placebo (rate ratio 0.78,95% CI 0.67,0.92) 3
• STIOLTO RESPIMAT (tiotropium/olodaterol) shows improved FEV1 response compared to monotherapy but did not demonstrate superiority to tiotropium alone for reducing exacerbation rates 3
• Maximizing bronchodilation with appropriate maintenance therapy, together with multidisciplinary disease management, can reduce exacerbations, hospitalizations, and readmissions 5