Are inhaled corticosteroids (ICS) effective as a first-line treatment for pulmonary fibrosis?

Inhaled Corticosteroids Are Not Effective as First-Line Treatment for Pulmonary Fibrosis

Inhaled corticosteroids (ICS) are not recommended as first-line treatment for pulmonary fibrosis as they have shown no benefit in improving lung function, reducing exacerbations, or improving mortality outcomes. 1

Evidence Against ICS in Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF)

• The American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) guidelines recommend against the routine use of inhaled corticosteroids for IPF 1
• Anti-inflammatory therapies, including corticosteroids, have not demonstrated efficacy in IPF, as the pathogenesis is now understood to involve aberrant wound healing rather than simply inflammation 2
• A Cochrane review found no evidence supporting corticosteroid treatment in patients with IPF/usual interstitial pneumonia 2

Cystic Fibrosis-Related Pulmonary Fibrosis

• The Cystic Fibrosis Foundation explicitly recommends against the routine use of inhaled corticosteroids to improve lung function and reduce exacerbations in patients with CF (Grade D recommendation) 1
• Multiple clinical trials involving 388 patients with CF showed no statistically significant improvement in lung function as measured by FEV1 or FVC with inhaled corticosteroids 1
• A withdrawal study involving 171 patients found no difference in time to exacerbations between patients continuing inhaled corticosteroids and those given placebo 1
• A Cochrane review of inhaled corticosteroids in CF concluded no benefits or harms resulted from their use 1

Specific Evidence on ICS Ineffectiveness

• Various inhaled corticosteroids have been studied including:

  • Beclomethasone (400-1500 mg) given two to four times daily 1
  • Fluticasone (400-500 mg) given twice daily 1
  • Budesonide (800 mg) given twice daily 1

• None of these regimens demonstrated statistically significant improvements in:

  • Lung function 1
  • Reduction in pulmonary exacerbations 1
  • Disease progression 1

Limited Indications for ICS in Pulmonary Disease

ICS may be considered in specific circumstances:

• In CF patients with concurrent asthma or allergic bronchopulmonary aspergillosis (ABPA) 1, 3
• In patients with pulmonary manifestations with wheezing, personal history of atopy, and/or bronchial hyper-responsiveness 3
• For acute exacerbations of IPF, systemic (not inhaled) corticosteroids may be considered, though evidence is very low quality 1

Alternative Treatment Approaches

For IPF:

• Pulmonary rehabilitation is recommended for the majority of patients (weak recommendation, low-quality evidence) 1
• Antifibrotic medications (pirfenidone, nintedanib) have shown more promise than anti-inflammatory approaches 4

For CF-related pulmonary disease:

• Dornase alfa is strongly recommended for patients with moderate to severe lung disease 1
• Inhaled hypertonic saline is recommended to improve lung function and reduce exacerbations 1
• Inhaled antibiotics (particularly tobramycin) for patients with Pseudomonas aeruginosa 1

Potential Harms of Corticosteroid Use

• While inhaled corticosteroids have fewer side effects than systemic corticosteroids, their lack of efficacy makes even minor risks unjustifiable 1
• Systemic corticosteroids carry significant risks including:
  • Abnormalities in glucose metabolism 1
  • Cataracts 1
  • Linear growth retardation in children 1
  • Increased risk of Pseudomonas aeruginosa colonization 1

Conclusion

The evidence consistently shows that inhaled corticosteroids provide no benefit as first-line treatment for pulmonary fibrosis, whether in the context of idiopathic pulmonary fibrosis or cystic fibrosis-related lung disease. Treatment should instead focus on disease-specific approaches with proven efficacy.