Pulmonary Fibrosis

Definition:

• Pulmonary fibrosis (PF) is a chronic, progressive interstitial lung disease characterized by fibrotic remodeling of the lung parenchyma, leading to reduced lung compliance, impaired gas exchange, and restrictive lung disease.
• In oncology, PF is often drug- or radiation-induced.

Etiology in Oncology

1. Chemotherapy-induced
   • Bleomycin → most classic cause
   • Busulfan
   • Methotrexate
   • Carmustine (BCNU), Lomustine (CCNU)
2. Radiation-induced
   • Thoracic irradiation → lung tissue within the radiation field
   • Risk increases with higher doses, concurrent chemo
3. Targeted / Immunotherapy
   • Checkpoint inhibitors (e.g., anti-PD-1/PD-L1, anti-CTLA-4) → immune-mediated pneumonitis → may progress to fibrosis if severe

Pathophysiology

• Injury to alveolar epithelial cells → inflammatory cascade → fibroblast proliferation → collagen deposition → irreversible scarring
• Cytokines involved: TGF-β, IL-1, TNF-α

Clinical Features

• Progressive dyspnea on exertion
• Non-productive dry cough
• Fatigue, hypoxemia
• Fine bibasilar inspiratory crackles on auscultation

Diagnosis

• High-resolution CT (HRCT): reticular opacities, honeycombing
• Pulmonary function tests (PFTs): restrictive pattern, ↓ DLCO
• History of chemotherapy, radiotherapy, or immunotherapy exposure

Management & Pharmacist Role

1. Prevention / Risk Mitigation
   • Limit cumulative doses of pulmonary-toxic chemo (e.g., bleomycin <400 IU)
   • Avoid high oxygen concentrations in patients receiving bleomycin
   • Dose adjustments in renal impairment (bleomycin excretion is renal)
2. Supportive Care
   • Oxygen therapy for hypoxemia
   • Pulmonary rehab for exercise tolerance
   • Monitor PFTs periodically during and after therapy
3. Pharmacologic Therapy
   • Corticosteroids for inflammatory or early pneumonitis
   • Anti-fibrotic agents (e.g., pirfenidone, nintedanib) under investigation
   • Avoid further lung-toxic agents
4. Drug-Specific Pearls
   • Bleomycin: Monitor baseline and serial DLCO, avoid high O₂, watch for pulmonary symptoms
   • Busulfan: Pulmonary function monitoring during conditioning for stem cell transplant
   • Methotrexate: Usually dose-dependent; monitor long-term use

High-Yield Pharmacist Pearls

• Cumulative dose and age increase risk (older adults higher risk)
• Early detection of pneumonitis can prevent progression to fibrosis
• Drug interactions: concurrent thoracic RT or other pulmonary-toxic drugs increase risk
• Patient counseling: report new cough, dyspnea, or exercise intolerance immediately