How many episodes of infective exacerbation of Chronic Obstructive Pulmonary Disease (COPD) should prompt caution when considering addition of Inhaled Corticosteroids (ICS) to Long-Acting Beta-Agonist (LABA)/Long-Acting Muscarinic Antagonist (LAMA) therapy?

Inhaled Corticosteroid Use in COPD: When to Avoid Adding ICS to LABA/LAMA Therapy

Patients with two or more infective exacerbations of COPD per year should warn clinicians against adding ICS to LABA/LAMA therapy due to the increased risk of pneumonia without significant clinical benefit in this population. 1

Understanding the Risk-Benefit Profile of ICS in COPD

Appropriate Indications for ICS in COPD

• ICS should be considered in combination with bronchodilators in patients with:
  • High risk for exacerbations with ≥2 moderate exacerbations or ≥1 hospitalization in the previous year 1
  • Blood eosinophil count ≥300 cells/μL (stronger indication) 2, 3
  • FEV1 <50-60% predicted 1
  • Asthma-COPD overlap syndrome (ACOS) 1, 2

Contraindications for ICS in COPD

• History of recurrent infective exacerbations (≥2 per year) 1
• Blood eosinophil count <100 cells/μL 2
• Risk factors for pneumonia:
  • Older age
  • Lower body mass index (BMI)
  • Greater overall fragility 2

Evidence-Based Decision Algorithm

1. Assess exacerbation history:

   • If patient has ≥2 infective exacerbations per year → Avoid ICS
   • If patient has ≥2 non-infective exacerbations per year → Consider ICS

2. Evaluate blood eosinophil count:

   • <100 cells/μL → Avoid ICS (high pneumonia risk, minimal benefit)
   • 100-300 cells/μL → Consider ICS based on other factors

   • 300 cells/μL → ICS may provide benefit (stronger indication)

3. Assess lung function:

   • FEV1 <50% predicted with frequent exacerbations → Consider ICS
   • FEV1 >50% predicted → Less likely to benefit from ICS

4. Consider pneumonia risk factors:

   • Presence of multiple risk factors → Exercise caution with ICS

Pneumonia Risk with ICS in COPD

The risk of pneumonia with ICS is significant and well-documented:

• ICS use increases pneumonia risk by 37-74% compared to LABA/LAMA alone 4, 5
• Number needed to harm: 33 patients treated for 1 year to cause one pneumonia 1
• Number needed to treat: 4 patients for 1 year to prevent one moderate-severe exacerbation 1

Clinical Implications and Recommendations

• For patients with recurrent infective exacerbations, prioritize LAMA/LABA dual therapy without ICS 1

• In patients with frequent exacerbations despite optimal LABA/LAMA therapy who require additional treatment:

  • Consider macrolide maintenance therapy (azithromycin or erythromycin) 1
  • For chronic bronchitic phenotype, consider roflumilast or N-acetylcysteine 1

• If ICS is currently prescribed in a patient with recurrent infective exacerbations:

  • Consider ICS withdrawal, especially if blood eosinophils <300 cells/μL 1
  • Monitor closely for worsening symptoms or exacerbations after withdrawal

Common Pitfalls to Avoid

1. Adding ICS automatically to all COPD patients with any exacerbation history without considering the nature of exacerbations (infective vs. non-infective)

2. Failing to monitor blood eosinophil counts when making decisions about ICS therapy

3. Not recognizing pneumonia risk factors in patients receiving ICS therapy

4. Using ICS as monotherapy in COPD (never appropriate) 1

5. Continuing ICS despite recurrent pneumonia events in high-risk patients

By carefully assessing exacerbation history, blood eosinophil counts, and pneumonia risk factors, clinicians can make more informed decisions about when to avoid adding ICS to LABA/LAMA therapy in COPD patients.