Can Inhaled Corticosteroid (ICS) inhalers increase the risk of respiratory infections, including pneumonia?

Inhaled Corticosteroids and Risk of Respiratory Infections

Yes, inhaled corticosteroids (ICS) significantly increase the risk of pneumonia and respiratory infections, particularly in COPD patients, with the risk being dose-dependent and greater in elderly patients with severe airflow obstruction.

Risk of Pneumonia in COPD Patients

The evidence clearly demonstrates that ICS use in COPD patients increases pneumonia risk:

• The 2023 Canadian Thoracic Society guideline explicitly acknowledges that "the incidence of pneumonia is higher with inhaled ICS-containing maintenance therapy, especially in individuals with severe and very severe disease" 1
• FDA labeling for fluticasone propionate warns that "physicians should remain vigilant for the possible development of pneumonia in patients with COPD" 2
• Clinical trials show significantly higher pneumonia rates in COPD patients on ICS:
  • 7% in patients receiving fluticasone/salmeterol versus 3% in those receiving salmeterol alone 2
  • 16% with fluticasone/salmeterol 500mcg/50mcg versus 9% with placebo in a 3-year trial 2

Risk Factors for ICS-Associated Pneumonia

Several factors increase the risk of developing pneumonia when using ICS:

• Age: Elderly patients (>65 years) have significantly higher pneumonia risk (9% vs 4% in younger patients) 3, 2
• Severity of airflow obstruction: Patients with FEV1 <50% predicted have greater risk 3
• Low BMI: Creates a high-risk profile when combined with advanced age and severe airflow obstruction 3
• ICS type: Fluticasone appears to carry higher pneumonia risk than budesonide 4
• ICS particle size: Standard particle size ICS is associated with higher pneumonia risk compared to extrafine particle ICS 5

Risk in Asthma Patients

The evidence regarding ICS and infection risk in asthma is mixed:

• A case-control study found a dose-response relationship between ICS strength and risk of pneumonia/lower respiratory tract infection in asthma patients, with those on high-dose ICS (≥1,000 μg) having 2.04 times increased risk 6
• However, a meta-analysis of pediatric trials found no increased risk of pneumonia with ICS use in children with asthma 7

Risk of Other Respiratory Infections

Beyond pneumonia, ICS may increase risk of other infections:

• The European Respiratory Society guidelines note "increased risk of NTM infection and pneumonia in adults with bronchiectasis and other chronic respiratory diseases who received ICS" 1
• Patients on chronic ICS are more likely to test positive for non-influenza respiratory viruses, particularly adenovirus (aOR 2.36) and respiratory syncytial virus (aOR 2.08) 8

Risk-Benefit Assessment

When considering ICS therapy, clinicians should weigh infection risks against benefits:

• The number needed to treat (NNT) with triple therapy versus dual bronchodilator therapy to prevent one moderate-to-severe exacerbation is 4 patients for 1 year
• The number needed to harm (NNH) to cause one pneumonia is 33 patients for 1 year 1
• For high-risk patients (elderly with severe airflow obstruction), consider LAMA/LABA combinations without ICS as initial therapy 3

Practical Recommendations

1. Assess individual risk factors before initiating ICS therapy, particularly in elderly patients with low BMI and severe airflow obstruction
2. Use the lowest effective ICS dose as higher doses increase pneumonia risk
3. Consider ICS type and formulation - budesonide and extrafine particle ICS may have lower pneumonia risk
4. Monitor closely for respiratory infections in high-risk patients on ICS therapy
5. Ensure pneumococcal and influenza vaccinations are up to date for all patients on ICS therapy

In summary, while ICS therapy provides important benefits in appropriate patients, clinicians must carefully consider and monitor the increased risk of respiratory infections, particularly pneumonia in COPD patients.