Recurrent Pneumonia on Breztri: Switch to LAMA/LABA Dual Therapy
In a COPD patient with recurrent pneumonia on Breztri (ICS/LAMA/LABA triple therapy), I recommend stepping down to LAMA/LABA dual bronchodilator therapy to eliminate the inhaled corticosteroid component that is driving the pneumonia risk.
Understanding the Pneumonia Risk with ICS-Containing Therapy
The recurrent pneumonia is almost certainly related to the inhaled corticosteroid (beclomethasone) component of Breztri. The evidence is clear:
- Pneumonia is a recognized class effect of all ICS-containing therapies in COPD, with no conclusive evidence of intra-class differences 1
- The number needed to harm is 33 patients treated for 1 year to cause one pneumonia 1
- ICS use increases pneumonia risk particularly in older patients and those with lower BMI 2
- In real-world practice, single-inhaler triple therapy increased severe pneumonia incidence by 50% (HR 1.50; 95% CI: 1.29-1.75) compared to dual bronchodilators 3
The Evidence Against Continuing Triple Therapy in This Context
While guidelines generally recommend against stepping down from triple therapy in high-risk patients, this recommendation assumes the patient is NOT experiencing recurrent pneumonia 1. The guideline states that withdrawing ICS can increase exacerbation risk, particularly in patients with eosinophils ≥300 cells/μL 1. However, recurrent pneumonia represents a clear harm that outweighs the theoretical benefit of continued ICS therapy.
The 2023 Canadian Thoracic Society guideline explicitly acknowledges this trade-off: "The clinical significance of increased pneumonia in individuals with COPD who use ICS-containing inhaled maintenance therapy must be balanced against concurrent documented improvements in lung function, health status, and a reduction in exacerbations" 1. In your patient, the balance has tipped toward harm.
Recommended Therapeutic Approach
Step 1: Switch to LAMA/LABA Dual Therapy
Discontinue Breztri and initiate a LAMA/LABA combination such as:
- Umeclidinium/vilanterol (Anoro Ellipta)
- Tiotropium/olodaterol (Stiolto Respimat)
- Glycopyrrolate/formoterol (Bevespi Aerosphere)
- Aclidinium/formoterol (Duaklir)
This eliminates the ICS-related pneumonia risk while maintaining dual bronchodilation 1.
Step 2: Assess Exacerbation Risk Factors
Check blood eosinophil count 1:
- If eosinophils <100 cells/μL: The patient likely had minimal ICS benefit anyway and should remain on LAMA/LABA 2
- If eosinophils 100-300 cells/μL: Monitor closely for exacerbations on LAMA/LABA
- If eosinophils ≥300 cells/μL: Higher risk of exacerbations after ICS withdrawal, but recurrent pneumonia still justifies the switch 1
Step 3: Add Non-ICS Exacerbation Prevention if Needed
If the patient continues to exacerbate on LAMA/LABA dual therapy (≥2 moderate or ≥1 severe exacerbations per year), consider adding 1:
Macrolide maintenance therapy (e.g., azithromycin 250-500 mg three times weekly) in appropriate patients who have:
- Normal QT interval on ECG
- No significant drug interactions
- No evidence of atypical mycobacterial infection 1
Roflumilast or N-acetylcysteine for patients with chronic bronchitic phenotype (chronic cough and sputum production) 1
Critical Monitoring Parameters
- Document exacerbation frequency over the next 6-12 months after the switch 1
- Monitor for pneumonia resolution after ICS withdrawal
- Verify proper inhaler technique with the new LAMA/LABA device 1
- Assess symptom control using validated tools (CAT score, mMRC dyspnea scale)
Common Pitfall to Avoid
Do not attempt to "power through" recurrent pneumonias by continuing triple therapy with added antibiotics or other interventions. The ICS is the modifiable risk factor here. While guidelines recommend against routine ICS withdrawal in high-risk patients, recurrent pneumonia is a specific clinical scenario where the harm clearly outweighs the benefit 1, 3. The real-world data showing a 50% increase in severe pneumonia with triple therapy versus dual bronchodilators supports this approach 3.