What is the role of combination Long-Acting Beta Agonist (LABA)/Inhaled Corticosteroid (ICS) therapy in Asthma/Chronic Obstructive Pulmonary Disease (COPD) overlap syndrome?

Role of LABA/ICS Combination Therapy in Asthma-COPD Overlap Syndrome

In patients with asthma-COPD overlap syndrome (ACOS), combination LABA/ICS therapy is strongly recommended as first-line maintenance treatment due to its ability to address both inflammatory and bronchoconstrictive components of the disease. 1

Pathophysiological Rationale

ACOS represents a condition where patients exhibit features of both asthma and COPD. This overlap creates unique treatment challenges that require addressing:

• Airway inflammation (predominant in asthma)
• Bronchial hyperresponsiveness (predominant in asthma)
• Airflow obstruction (predominant in COPD)
• Risk of exacerbations (present in both conditions)

Diagnostic Criteria for ACOS

Several consensus guidelines provide criteria for diagnosing ACOS:

• Spanish Consensus: Two major criteria (increase in FEV₁ ≥15% and ≥400 mL, eosinophilia in sputum, history of asthma) or one major and two minor criteria (elevated IgE, atopy history, positive bronchodilator response) 1
• Czech Guidelines: Similar major/minor criteria system including bronchodilator test positivity, FeNO levels, and eosinophilia 1
• Japanese Guidelines: Paroxysmal dyspnoea, cough/wheeze worse at night/early morning, atopy, and peripheral blood/sputum eosinophilia 1

Treatment Algorithm for ACOS

1. Initial Assessment:

   • Confirm ACOS diagnosis using established criteria
   • Assess symptom burden (CAT ≥10, mMRC ≥2)
   • Evaluate lung function (FEV₁ <80% predicted)
   • Determine exacerbation history

2. First-line Treatment:

   • LABA/ICS combination therapy regardless of COPD severity 1
   • This approach is recommended by multiple guidelines including Japanese Respiratory Society, GINA/GOLD consensus, and Australian Asthma Management Handbook 1

3. For Persistent Symptoms/Exacerbations:

   • Escalate to triple therapy by adding LAMA to LABA/ICS 1
   • Consider roflumilast if FEV₁ <50% predicted and chronic bronchitis features are present 1

Evidence Supporting LABA/ICS in ACOS

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

1. Pathophysiological Rationale: ICS targets inflammation while LABA addresses bronchoconstriction 2

2. Clinical Effectiveness:

   • A 12-week study comparing once-daily fluticasone furoate/vilanterol with twice-daily fluticasone propionate/salmeterol showed significant improvement in FEV₁ with the combination therapy compared to baseline 3
   • LABA/ICS combinations have demonstrated additive and potentially synergistic effects 4

3. Guideline Consensus: Multiple international guidelines recommend LABA/ICS as the foundation of ACOS treatment 1

Specific LABA/ICS Considerations

• Dosing: Typically twice daily for most combinations, though newer options like fluticasone furoate/vilanterol offer once-daily dosing 3
• Safety: Monitor for increased risk of pneumonia with ICS use, particularly in COPD component 5, 1
• Formulations: Available as fixed-dose combinations (e.g., fluticasone/salmeterol, budesonide/formoterol) 5

Important Caveats and Monitoring

• Pneumonia Risk: ICS use in COPD patients increases pneumonia risk; monitor closely 1
• Local Side Effects: Oral candidiasis, hoarseness, and dysphonia may occur; advise patients to rinse mouth after use 5
• Systemic Effects: Monitor for potential systemic corticosteroid effects with long-term use 2
• Never Use LABA Alone: LABAs should never be used as monotherapy in patients with asthma component due to increased risk of severe exacerbations 6, 5

Biomarkers to Guide Therapy

Certain biomarkers may help identify ACOS patients who will respond well to ICS:

• Exhaled nitric oxide concentration
• Percentage of peripheral eosinophils 7

In summary, LABA/ICS combination therapy represents the cornerstone of treatment for patients with ACOS, addressing both the inflammatory and bronchoconstrictive components of the disease. For patients with persistent symptoms or exacerbations, escalation to triple therapy by adding a LAMA is recommended.