What is the first line treatment for Chronic Obstructive Pulmonary Disease (COPD)/Asthma overlap?

First-Line Treatment for COPD/Asthma Overlap Syndrome

For patients with COPD/Asthma overlap syndrome, inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA) combination therapy is the recommended first-line treatment. 1

Diagnostic Considerations

Before initiating treatment, confirm the diagnosis of COPD/Asthma overlap by identifying:

• Age typically older (mean 64.6 years) 1
• Persistent airflow limitation with significant reversibility (≥15% and ≥400 mL) 1
• Blood eosinophilia (≥300 eosinophils/μL) 1
• History of asthma or atopy 1
• Smoking history (mean 38.7 pack-years) 1

Treatment Algorithm

Step 1: First-Line Therapy

• ICS/LABA combination 1, 2
  • Targets both eosinophilic inflammation (ICS) and bronchoconstriction (LABA)
  • Examples: fluticasone/salmeterol or budesonide/formoterol 3
  • Dosing: Twice daily administration 3

Step 2: Inadequate Response

If symptoms persist or exacerbations continue:

• Add LAMA to create triple therapy (ICS/LABA/LAMA) 1, 2
  • Recommended for patients at high risk of exacerbations with moderate to high symptom burden 2
  • Triple therapy has shown mortality benefits in high-risk patients 1

Step 3: Continued Exacerbations

For patients still experiencing exacerbations on triple therapy:

• Consider adding roflumilast (if FEV₁ <50% predicted and chronic bronchitis) 2
• Consider macrolide therapy (in former smokers) 2

Clinical Considerations

Advantages of ICS/LABA First-Line Therapy

• Addresses both key pathophysiological mechanisms:
  • ICS targets eosinophilic inflammation common in asthma component 4
  • LABA addresses bronchoconstriction present in both conditions 4
• Reduces exacerbation rates more effectively than monotherapy 4
• Potential synergistic effects between ICS and LABA components 5

Important Monitoring

• Assess for pneumonia risk, which may be increased with ICS use 2
• Monitor for oral candidiasis; advise patients to rinse mouth after inhalation 3
• Evaluate bone mineral density periodically with long-term ICS use 3
• Check for development of glaucoma or cataracts with prolonged ICS therapy 3

Cautions and Contraindications

• LABA monotherapy should never be used in patients with asthma component due to increased risk of asthma-related events including death 3, 4
• ICS/LABA should not be used for acute symptom relief 3
• Use with caution in patients with cardiovascular disorders due to beta-adrenergic stimulation 3

Rationale for ICS/LABA as First-Line

The recommendation for ICS/LABA as first-line therapy is based on:

1. Multiple guidelines including Spanish COPD consensus, Japanese Respiratory Society, and Australian Asthma Management Handbook 1
2. GOLD guidelines noting that LABA/ICS may be first choice for patients with features suggestive of asthma-COPD overlap 2
3. Evidence that ICS/LABA combination provides superior control of symptoms and reduction in exacerbations compared to monotherapy 4, 5
4. Recognition that ACOS patients have worse outcomes (more exacerbations, poorer quality of life) than those with either condition alone, requiring more aggressive initial therapy 6

This approach prioritizes targeting the dual inflammatory and bronchoconstrictive nature of COPD/Asthma overlap, with escalation to triple therapy when needed for patients with persistent symptoms or exacerbations.