Should an inhaled corticosteroid (ICS) be started in a patient with chronic obstructive pulmonary disease (COPD) and a history of exacerbations, despite adherence to formoterol (a long-acting beta2-adrenergic receptor agonist (LABA))/aclidinium (a long-acting muscarinic antagonist (LAMA)), to reduce the risk of future exacerbations?

Inhaled Corticosteroid Therapy in COPD with History of Exacerbations

An inhaled corticosteroid (ICS) should be started in this patient to reduce his risk of future exacerbations, despite his low blood eosinophil count. 1

Assessment of Current Status

This 65-year-old male patient presents with:

• History of two COPD exacerbations in the past year
• Currently on dual bronchodilator therapy (formoterol/aclidinium)
• Blood eosinophil count of 125 cells/µL
• Comorbidities: hypertension, dyslipidemia, CAD, COPD
• Former smoker

Rationale for Adding ICS Therapy

Exacerbation History

• The patient has experienced two exacerbations in the past year despite adherence to LABA/LAMA therapy
• According to GOLD guidelines, patients with persistent exacerbations despite appropriate maintenance bronchodilator therapy should receive ICS 1
• The American College of Chest Physicians and Canadian Thoracic Society strongly recommend maintenance combination ICS/LABA therapy compared to LABA monotherapy to prevent acute exacerbations (Grade 1C) 2

Blood Eosinophil Considerations

• While the patient's eosinophil count is 125 cells/µL (relatively low), the history of multiple exacerbations despite optimal dual bronchodilator therapy outweighs this consideration
• European guidelines indicate that ICS is recommended in patients with frequent exacerbations despite appropriate bronchodilator therapy, particularly with FEV1 <50-70% predicted 2
• The primary benefit of ICS in this case is exacerbation reduction rather than eosinophil-driven inflammation 3

Benefit vs. Risk Analysis

Benefits

• Reduced risk of future exacerbations
• Improved quality of life
• Potential reduction in hospitalization risk
• Slowed decline in health-related quality of life 2

Risks

• Increased risk of pneumonia, particularly in:
  • Older patients (patient is 65)
  • Lower BMI patients
  • Higher ICS doses 3
• Other potential side effects: oral candidiasis, hoarseness, dysphonia, bruising 2

Implementation Approach

1. Add ICS to current therapy:

   • Consider triple therapy (LABA/LAMA/ICS) since patient is already on LABA/LAMA
   • The ERS/ATS guidelines support this escalation in patients with history of exacerbations 2

2. ICS Selection:

   • Consider budesonide over fluticasone due to potentially lower pneumonia risk, especially given patient's age 1
   • Start with appropriate dosing based on severity

3. Monitoring:

   • Regular follow-up to assess:
     • Exacerbation frequency
     • Pneumonia development
     • Symptom control
     • Adverse effects

Important Considerations

• While there is a risk of pneumonia with ICS use, this must be balanced against the clear benefit of reducing exacerbations in this patient who has already demonstrated poor control on dual bronchodilator therapy
• The patient's cardiovascular comorbidities make exacerbation prevention particularly important
• If pneumonia occurs or the patient shows no improvement in exacerbation frequency after 3-6 months, reassessment of ICS therapy would be warranted

In conclusion, despite the relatively low eosinophil count, this patient's history of multiple exacerbations while on optimal LABA/LAMA therapy makes him an appropriate candidate for ICS addition to reduce future exacerbation risk.