Treatment of UIP/IPF Pattern ILD (92-Year-Old Female)

Understanding the HRCT Impression

• Bilateral basal, subpleural interstitial lung disease with reticulation, honeycombing, and ground-glass opacities - a classic UIP pattern
• Possible differentials: IPF (UIP pattern) vs fibrotic NSIP
• Subpleural nodule right apex (needs separate follow-up - see below)
• Mild mediastinal lymphadenopathy
• T12 wedge compression fracture

Step 1: Complete the Diagnostic Workup Before Treatment

Key point: In a 92-year-old, transbronchial cryobiopsy or surgical lung biopsy carries very high risk and is generally not recommended unless absolutely necessary to change management. The HRCT pattern is sufficient for clinical diagnosis of probable UIP in this age group.

Step 2: Pharmacological Treatment

A. Antifibrotic Therapy (First-Line for IPF/UIP)

1. Nintedanib (Ofev) - Preferred option

• Mechanism: Tyrosine kinase inhibitor (blocks FGFR, VEGFR, PDGFR) - inhibits fibroblast proliferation and extracellular matrix deposition
• Dose: 150 mg twice daily orally with food; reduce to 100 mg BD if not tolerated
• Evidence: INPULSIS-1 and INPULSIS-2 trials showed significant reduction in FVC decline at 52 weeks vs placebo
• Main side effect: Diarrhea (>60% of patients) - manage with loperamide; hepatotoxicity - monitor LFTs
• Note for elderly: Dose reduction to 100 mg BD is often needed in patients with low body weight or hepatic impairment

2. Pirfenidone (Esbriet) - Alternative

• Mechanism: Reduces TGF-β-stimulated fibroblast proliferation and collagen production
• Dose: Start 267 mg TDS, increase weekly to 801 mg TDS (2403 mg/day) by week 3
• Evidence: ASCEND + CAPACITY trials showed reduced FVC decline and improved progression-free survival
• Main side effects: GI (nausea, anorexia), photosensitivity rash, hepatotoxicity
• Note: Photosensitivity requires sun avoidance; GI side effects often limit tolerance in the elderly

3. Nerandomilast (Jascayd) - Newly FDA-approved (October 2025)

• Mechanism: First-in-class PDE4B inhibitor - upregulates cAMP, dampening fibrotic and inflammatory signaling (inhibits TGF-β1 and fibroblast proliferation)
• Dose: 9 mg or 18 mg twice daily
• Evidence: FIBRONEER-IPF Phase 3 RCT (NEJM 2025, PMID 40387033) - nerandomilast 18 mg reduced FVC decline by 68.8 mL more than placebo at 52 weeks; can be used on top of nintedanib or pirfenidone
• FDA also approved Dec 2025 for Progressive Pulmonary Fibrosis (PPF)
• Main side effect: Diarrhea (41% with 18 mg dose)
• Note: This is the first new IPF therapy in over 10 years - can be added as combination therapy

In a 92-year-old patient, the choice should be based on:

• Comorbidities: Nintedanib is preferred in those with GI disease; pirfenidone if GI is fragile
• Polypharmacy: Both are CYP3A4 substrates - check for drug interactions
• Goals of care: If patient/family prefer comfort over disease slowing, antifibrotic therapy may reasonably be deferred

Drugs NOT Recommended (Avoid)

• Prednisone/azathioprine/NAC combination - shown to increase mortality (PANTHER trial)
• NAC monotherapy - no benefit
• Warfarin, sildenafil (for IPF-PH), bosentan, ambrisentan - all lack benefit or cause harm in IPF

Step 3: Non-Pharmacological Management

Step 4: Management of Specific Findings on This Report

Subpleural Nodule (1.2 x 1.3 cm, Right Apex)

• LDCT follow-up in 3 months to assess growth
• Given age 92 and bilateral ILD, invasive biopsy should only be pursued if it would genuinely change management
• Discuss with patient/family regarding goals of care

T12 Wedge Collapse

• Likely osteoporotic compression fracture (very common in elderly females)
• Refer to orthopedics or spine team
• Consider DEXA scan, calcium/vitamin D supplementation, bisphosphonate therapy if appropriate
• Assess pain; consider analgesia and physiotherapy

Mediastinal Lymphadenopathy (Subcentimeter)

• Subcentimeter nodes are often reactive in ILD and do not require immediate workup
• Monitor on follow-up CT

Step 5: Palliative and Supportive Care

• Symptom management: Opioids (low-dose oral morphine) for severe dyspnea; benzodiazepines for anxiety
• Cough suppression: Low-dose codeine or gabapentin for chronic cough
• Advance care planning: Document goals of care, resuscitation preferences, and ventilation wishes
• Palliative care referral if symptoms are distressing or disease is rapidly progressive
• Acute exacerbation treatment (if it occurs): High-dose corticosteroids (e.g., methylprednisolone 0.5-1 g/day IV for 3 days), though evidence is limited and prognosis is poor

Summary Treatment Algorithm for This Patient

92-year-old female, UIP/probable IPF on HRCT
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Complete workup (PFTs, ANA panel, Echo)
MDT discussion to confirm UIP/IPF vs CTD-ILD
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     ┌───┴────┐
  CTD-ILD?   IPF/UIP?
  → Treat    → Antifibrotic:
  underlying    Nintedanib 150 mg BD  OR
  CTD +         Pirfenidone 801 mg TDS
  antifibrotic  (consider nerandomilast
                as add-on)
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  Non-pharmacological:
  O2, Pulm Rehab, Vaccines
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  Palliative/Supportive care (integral, not end-stage)
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  Monitor: PFTs every 3-6 months, CT at 12 months
  Nodule: Follow-up LDCT at 3 months
  T12 fracture: Orthopedic/bone health management