Why are corticosteroids (steroids) contraindicated in patients with pulmonary fibrosis?

Why Steroids Are Contraindicated in Pulmonary Fibrosis

Corticosteroids should not be used routinely in idiopathic pulmonary fibrosis (IPF) because they provide no survival benefit, cause substantial morbidity, and may actually increase mortality risk. 1

The Evidence Against Steroid Use in IPF

Lack of Efficacy

• No prospective, randomized, double-blind, placebo-controlled trial has ever demonstrated efficacy of corticosteroids in treating IPF 1
• No survival benefit has been demonstrated in patients treated with corticosteroids in controlled trials 1
• Only 10-30% of patients show any improvement with corticosteroids, and these responses are typically partial and transient, with few achieving sustained complete remissions 1
• The efficacy of corticosteroids remains unproven despite their use for over four decades, and there is no evidence that any form of therapy alters the natural history of IPF 2

Significant Harm and Morbidity

• Corticosteroid monotherapy is associated with substantial long-term morbidity 1
• All patients in prospective studies experienced at least one steroid-induced side effect 3
• Common adverse effects include abnormalities in glucose metabolism, cataracts, linear growth retardation (in children), osteoporosis, diabetes, and increased susceptibility to infections 1
• Weight loss during the initial 3 months of steroid therapy was associated with increased mortality (42% of patients who died versus 14% of survivors) 3

Increased Mortality Risk

• Recent evidence suggests steroid use may be associated with increased risk of inpatient mortality or transplantation (OR 4.11; 95% CI 1.00-16.83) in acute exacerbations of fibrotic interstitial lung disease 4
• Median survival was reduced in the steroid group (221 vs. 520.5 days) with increased risk of all-cause mortality (HR 3.25; 95% CI 1.56-6.77) 4
• Triple therapy combining prednisone, azathioprine, and N-acetylcysteine showed increased risk of death and hospitalizations 5

Why the Pathophysiology Doesn't Support Steroid Use

IPF Is Not Primarily an Inflammatory Disease

• Current research indicates that IPF mechanisms reflect abnormal, dysregulated wound healing within the lung, involving increased activity of profibrogenic growth factors rather than inflammation 6
• The disease is characterized by progressive fibrosis that cannot be reversed, making anti-inflammatory approaches fundamentally misguided 1
• The continued use of corticosteroids historically was justified only because of the lack of a more effective alternative, not because of proven benefit 6

Official Guideline Recommendations

French Practical Guidelines (2014)

It is recommended NOT to use corticosteroid therapy (with or without immunomodulator therapy) in patients with a definite diagnosis of IPF, except in the context of acute exacerbation of the disease 1

American Thoracic Society/European Respiratory Society (2000)

• Combination corticosteroid and immunomodulator therapy (e.g., azathioprine or cyclophosphamide) cannot be recommended due to methodological biases or conflicting results 1
• The only potential exception is low-dose oral corticosteroids (up to 10 mg prednisone per day) sometimes proposed to alleviate incapacitating cough 1

Limited Exception: Acute Exacerbations Only

• High-dose corticosteroid therapy is proposed only for treating patients with acute exacerbation of IPF, not for chronic management 1
• Even in acute exacerbations, the evidence remains limited and controversial, with recent data suggesting potential harm 4

Clinical Practice Changes

• Since publication of treatment guidelines, there has been a modest but statistically significant reduction in overall corticosteroid use (22.2% vs. 17.7%; adjusted OR 0.65) 7
• However, corticosteroid monotherapy remained the most commonly prescribed regimen among treated patients despite lack of established benefit 7
• The reasons for continued use of corticosteroid monotherapy in the majority of treated patients warrant further investigation given the risks and lack of benefit 7

Key Pitfall to Avoid

Do not confuse IPF with other inflammatory lung conditions where steroids are beneficial (such as asthma, COPD exacerbations, ABPA, or organizing pneumonia), as these represent fundamentally different pathophysiologic processes 5, 8