What is the first‑line treatment for an older adult with idiopathic pulmonary fibrosis presenting with progressive dyspnea, a restrictive pattern on pulmonary function testing, and characteristic high‑resolution computed tomography findings?

First-Line Treatment for Idiopathic Pulmonary Fibrosis

Initiate antifibrotic therapy with either pirfenidone or nintedanib as first-line treatment for an older adult with confirmed IPF presenting with progressive dyspnea, restrictive physiology, and characteristic HRCT findings. 1, 2

Antifibrotic Agent Selection

Both pirfenidone and nintedanib are equally recommended as first-line therapy for IPF with strong evidence supporting their use. 1, 2 The choice between these agents should be based on:

• Pirfenidone: Preferred when FVC >50% predicted and DLCO >35% predicted, with mechanism involving anti-inflammatory, antioxidative, and antiproliferative effects 1, 3
• Nintedanib: Blocks tyrosine-kinase pathways (PDGFR, FGFR, VEGFR) that drive fibrogenesis, with similar efficacy profile 1

Both agents slow FVC decline and reduce acute exacerbation risk, though neither has definitively proven mortality benefit beyond lung transplantation. 4, 5

Treatment Initiation Protocol

Dosing Strategy

• Pirfenidone: Administer 2,403 mg/day divided into three doses with food 3

  • Gradual dose titration recommended to minimize gastrointestinal side effects 1

• Nintedanib: Standard dosing per FDA labeling, administered with food 1

Baseline Assessment Requirements

Before initiating therapy, document:

• Baseline FVC and DLCO measurements (essential for monitoring progression) 1, 2
• Liver function tests (required for safety monitoring) 1, 2
• Exclude alternative diagnoses including hypersensitivity pneumonitis, connective tissue disease-associated ILD, and chronic hypersensitivity pneumonia 6

Monitoring Requirements

Pulmonary Function Surveillance

• Spirometry (FVC) and DLCO every 3-6 months to assess treatment response and detect disease progression 1, 2
• Serial FVC changes predict mortality effectively and guide treatment decisions 5
• Quantitative CT analysis provides objective disease progression measurement when available 1

Safety Monitoring

• Pirfenidone: Liver function tests monthly for first 6 months, then every 3 months thereafter 1, 2
• Nintedanib: Similar hepatic monitoring schedule given potential for transaminase elevation 1

Adverse Effect Management

Pirfenidone-Specific Issues

Common adverse effects include nausea, rash, fatigue, diarrhea, photosensitivity, and mild transaminase elevation. 1, 3 Management strategies:

• Gradual dose titration to minimize gastrointestinal symptoms 1
• Take medication with food 1
• Strict sun protection and avoidance of UV exposure 1

Nintedanib-Specific Issues

Gastrointestinal effects predominate, with diarrhea occurring 2.8-fold more frequently than placebo, nausea 3.1-fold, vomiting 3.6-fold, and abdominal pain 4.2-fold. 7 Management includes:

• Dose reduction (required in approximately 8% of patients) 1
• Temporary treatment interruption for intolerable toxicity 1, 7

Critical Contraindications

Avoid the following interventions that increase mortality or lack benefit:

• Triple therapy (prednisone + azathioprine + N-acetylcysteine) is absolutely contraindicated due to increased mortality 1, 2, 7
• Corticosteroid monotherapy should be reserved only for severe incapacitating cough or acute exacerbations, not routine IPF management 1, 2
• Ambrisentan is contraindicated in IPF due to lack of benefit and potential harm 1, 2
• Oral vitamin K antagonists are not recommended for anticoagulation in IPF patients 1

Supportive Care Measures

Preventive Interventions

• Annual influenza and pneumococcal vaccinations are strongly recommended for all IPF patients 1, 2, 7

Symptomatic Management

• Long-term supplemental oxygen indicated for patients with severe resting hypoxemia 1, 2, 7
• Structured pulmonary rehabilitation improves exercise capacity and quality of life 1

Advanced Therapy Consideration

• Lung transplantation should be considered for eligible patients <65 years with severe or rapidly worsening disease 1, 2, 7
• Transplantation remains the only curative intervention and sole treatment proven to increase life expectancy 4, 8

Disease Progression Criteria

Progressive disease is defined by at least two of three criteria occurring within the past year: 6

• Worsening respiratory symptoms (progressive dyspnea, cough) 6
• Radiological progression on HRCT 6
• Physiological progression (≥10% FVC decline over 24 months or ≥5% over 12 months) 6, 7

Common Pitfalls to Avoid

The most critical error is delaying antifibrotic therapy initiation while pursuing unnecessary additional testing once IPF diagnosis is established with characteristic HRCT findings. 6 The UIP pattern on HRCT (honeycombing with or without traction bronchiectasis, subpleural and basal predominant distribution) in a patient >60 years with unexplained bilateral pulmonary fibrosis and bibasilar crackles establishes IPF diagnosis without requiring biopsy. 6

Another common mistake is prescribing antacid medications specifically to improve respiratory outcomes—this has a conditional recommendation against such use based on very low quality evidence. 6 Antacids should only be used when patients have symptomatic gastroesophageal reflux disease requiring treatment per GER-specific guidelines. 6