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

From the Guidelines

Treatment of COPD exacerbation should prioritize a multi-faceted approach including bronchodilation, anti-inflammatory therapy, and supportive care, with the most recent and highest quality evidence supporting the use of short-acting bronchodilators, systemic corticosteroids, and antibiotics when indicated, as recommended by the 2021 American Family Physician guideline 1. The cornerstone medications for COPD exacerbation treatment include:

• Short-acting bronchodilators such as albuterol (2.5-5 mg via nebulizer or 4-8 puffs via MDI every 4-6 hours) and ipratropium (0.5 mg via nebulizer or 4-8 puffs via MDI every 4-6 hours)
• Systemic corticosteroids, typically prednisone 40 mg daily for 5 days, which improve lung function, oxygenation, and shorten recovery time and hospitalization duration 1
• Antibiotics, when indicated, with options including amoxicillin-clavulanate (875/125 mg twice daily), azithromycin (500 mg on day 1, then 250 mg daily for 4 days), or doxycycline (100 mg twice daily) for 5-7 days, which can shorten recovery time and reduce the risk of early relapse, treatment failure, and hospitalization duration 1 Supplemental oxygen should be provided to maintain oxygen saturation at 88-92%, and for severe exacerbations, non-invasive ventilation (NIV) may be necessary, as recommended by the 2017 European Respiratory Society/American Thoracic Society guideline 1. After the acute phase, patients should transition back to maintenance therapy with long-acting bronchodilators, and addressing exacerbations promptly is crucial as repeated episodes accelerate lung function decline and increase mortality risk in COPD patients. Key considerations for treatment decisions include:
• Clinical judgment and patient preferences and values
• Shared decision-making by the patient and clinician
• The need for further research into patient-oriented outcomes, such as clinical cure/clinical failure, quality of life, and repeat exacerbations, as highlighted by the 2021 American Family Physician guideline 1.

From the FDA Drug Label

The effect of roflumilast 500 mcg once daily on COPD exacerbations was evaluated in five 1-year trials (Trials 3,4,5,6 and 9).

Two of the trials (Trials 3 and 4) conducted initially enrolled a population of patients with severe COPD (FEV 1 ≤50% of predicted) inclusive of those with chronic bronchitis and/or emphysema who had a history of smoking of at least 10 pack years

The rate of moderate or severe COPD exacerbations was a co-primary endpoint in both trials

Exploratory analyses of the results of Trials 3 and 4 identified a subpopulation of patients with severe COPD associated with chronic bronchitis and COPD exacerbations within the previous year that appeared to demonstrate a better response in the reduction of the rate of COPD exacerbations compared to the overall population

The treatment of COPD exacerbation with roflumilast 500 mcg once daily may be effective in reducing the rate of moderate or severe COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of COPD exacerbations. However, the overall evidence is not conclusive, and the results are based on exploratory analyses of subpopulations. Key points to consider:

• Patient population: Severe COPD associated with chronic bronchitis
• Dosing: Roflumilast 500 mcg once daily
• Efficacy: Reduction in rate of moderate or severe COPD exacerbations
• Study design: Five 1-year trials, including Trials 3,4,5,6, and 9 2

From the Research

Treatment of COPD Exacerbation

• The treatment of COPD exacerbation involves the use of various pharmacologic agents, including bronchodilators, corticosteroids, and antibiotics 3, 4, 5, 6.
• According to the American Thoracic Society Clinical Practice Guideline, the use of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy is strongly recommended over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance 3.
• The guideline also conditionally recommends the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year 3.
• Azithromycin has been shown to be effective in reducing the number of exacerbations in patients with COPD, particularly in those with frequent exacerbations and blood eosinophilia over 2% 4.
• The use of prophylactic antibiotics, such as azithromycin, has been associated with a reduction in exacerbations and improvement in quality of life in patients with COPD 4, 5.
• Short-acting bronchodilators, such as β2-agonists and ipratropium, are commonly used in the management of acute exacerbations of COPD in the hospital setting, but the evidence for their use is limited and heterogeneous 6.

Pharmacologic Management

• The pharmacologic management of COPD exacerbation involves the use of various agents, including:
  • Bronchodilators: LABA, LAMA, and short-acting β2-agonists 3, 6.
  • Corticosteroids: inhaled corticosteroids (ICS) and oral corticosteroids 3.
  • Antibiotics: azithromycin and other prophylactic antibiotics 4, 5.

Clinical Recommendations

• The American Thoracic Society Clinical Practice Guideline provides recommendations for the pharmacologic treatment of COPD, including the use of LABA/LAMA combination therapy and triple therapy with ICS/LABA/LAMA 3.
• The GOLD2020 guidelines recommend the use of azithromycin (250 mg or 500 mg daily three times a week) for 1 year in COPD patients to reduce the number of exacerbations 4.