What is the initial treatment approach for pulmonary fibrosis?

Initial Treatment Approach for Pulmonary Fibrosis

The initial treatment for pulmonary fibrosis depends critically on determining whether the patient has idiopathic pulmonary fibrosis (IPF) or a systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD), as these require fundamentally different therapeutic approaches: antifibrotic therapy for IPF versus immunosuppressive therapy for SARD-ILD. 1

Step 1: Establish the Underlying Etiology

Before initiating any treatment, you must differentiate between IPF and other causes of pulmonary fibrosis, as this determines the entire treatment strategy:

Screen for Connective Tissue Disease

• Obtain serologic testing including rheumatoid factor, anti-CCP antibodies, ANA, anti-Scl-70, anti-Jo-1, and other myositis-specific antibodies to identify SARD-ILD 1
• Evaluate for environmental/occupational exposures including organic antigens, silica, asbestos, and drug toxicity 1
• Obtain high-resolution CT (HRCT) to assess for usual interstitial pneumonia (UIP) pattern versus non-UIP patterns 2, 1

Step 2: Treatment Based on Etiology

For IPF with UIP Pattern

Initiate antifibrotic therapy immediately with either pirfenidone or nintedanib 1, 3, 4:

Pirfenidone Dosing

• Titrate over 14 days: Days 1-7: 267 mg three times daily; Days 8-14: 534 mg three times daily; Day 15 onward: 801 mg three times daily (total 2,403 mg/day) 4
• Take with food at the same time each day 4
• Monitor liver function tests before initiating and monthly for the first 6 months, then every 3 months 2, 4

Nintedanib Alternative

• Nintedanib is equally effective at slowing FVC decline and can be used as an alternative first-line agent 1, 3
• Both agents reduce the rate of FVC decline by approximately 44-57% annually 5

Critical caveat: Do NOT use corticosteroids or immunosuppressive therapy for IPF, as these are ineffective and potentially harmful 2, 1, 5

For SARD-ILD with UIP Pattern

Initiate mycophenolate as first-line immunosuppressive therapy 1, 5:

• Mycophenolate is the preferred agent across all SARD-ILD subtypes, including those with UIP pattern 1
• Alternative options include rituximab (conditionally recommended) 1 or cyclophosphamide (conditionally recommended, typically not combined with other agents) 1
• For systemic sclerosis-ILD specifically, nintedanib is conditionally recommended as an additional first-line option 1

Step 3: Implement Supportive Care Simultaneously

Regardless of etiology, initiate these measures at diagnosis:

Vaccinations

• Annual influenza vaccination 2
• Pneumococcal vaccination (polysaccharide vaccine) 2

Oxygen Therapy

• Long-term oxygen therapy for severe hypoxemia at rest (PaO2 <55 mmHg or oxygen saturation <88%) 2

Pulmonary Rehabilitation

• Initiate respiratory rehabilitation program for patients with exercise limitation causing significant impairment 2
• Includes exercise training, smoking cessation, psychosocial support 2

Lung Transplantation Evaluation

• Refer early for transplant evaluation if age <65 years and disease is severe or worsening 2
• Consider at diagnosis if DLCO <39% predicted or FVC declines >10% over 6 months 2

Step 4: Monitor for Disease Progression

Establish regular monitoring every 3-6 months 2, 3:

• Pulmonary function testing (FVC, DLCO) every 4-6 months or sooner if clinically indicated 2
• Six-minute walk test every 4-6 months 2
• Annual HRCT if clinical suspicion of worsening or risk of lung cancer 2

Define Progressive Pulmonary Fibrosis (PPF)

Monitor for at least 2 of the following within the past year 2:

1. Worsening respiratory symptoms
2. Absolute FVC decline >5% predicted OR absolute DLCO decline >10% predicted
3. Radiological progression (increased traction bronchiectasis, new ground-glass opacity with traction bronchiectasis, new/increased reticulation, new/increased honeycombing, increased lobar volume loss)

Step 5: Adjust Treatment for Progressive Disease

For SARD-ILD Developing PPF Despite Immunosuppression

• Add nintedanib to ongoing immunosuppressive therapy 1, 3
• Nintedanib reduces annual FVC decline by 106.2 mL/year in CTD-ILD, 141.7 mL/year in fibrotic NSIP, and 252.8 mL/year in fibrotic occupational lung disease 2

For IPF with Acute Exacerbation

• High-dose corticosteroids are commonly used despite lack of controlled trial evidence 2
• Consider intravenous cyclophosphamide as some observations suggest benefit 2

Common Pitfalls to Avoid

Do not delay treatment waiting for "stability": FVC decline in IPF is nearly linear regardless of baseline lung function, and early treatment is critical to preserve lung function 6

Do not use immunosuppression for IPF: This is a fundamental error that can cause harm 1, 5

Do not discontinue antifibrotic therapy for mild side effects: Dose adjustment is effective at managing side effects without compromising efficacy 6. For gastrointestinal symptoms or photosensitivity, consider temporary dose reduction rather than discontinuation 4

Do not miss the 14-day titration period for pirfenidone: Patients who miss ≥14 days must restart the full titration regimen 4