Idiopathic pulmonary fibrosis

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Pathophysiology - Scarred for Life

  • Hallmark: Biopsy reveals Usual Interstitial Pneumonia (UIP), a pattern of progressive fibrosis.
  • Mechanism: Begins with repetitive, microscopic injury to alveolar epithelial cells, leading to aberrant wound healing.
  • Key Mediators: Involves pro-fibrotic cytokines, primarily TGF-β1, which stimulates fibroblast proliferation and excessive extracellular matrix (collagen) deposition.

⭐ Classic finding is spatial & temporal heterogeneity: patches of late-stage honeycomb fibrosis alternate with less affected or normal lung tissue.

UIP Histology: Fibroblastic Foci & Honeycomb Change

Clinical Presentation & Diagnosis - Can't Catch a Breath

  • Presentation: Insidious onset of dyspnea on exertion (DOE) and a persistent dry cough, typically for > 6 months.
  • On Examination:
    • Fine, bibasilar inspiratory crackles ("Velcro-like" rales).
    • Digital clubbing is present in up to 50% of cases.
  • Pulmonary Function Tests (PFTs):
    • Classic restrictive pattern: ↓ FVC, ↓ TLC, with a normal or ↑ FEV1/FVC ratio.
    • Markedly ↓ DLCO (diffusing capacity for carbon monoxide).
  • High-Resolution CT (HRCT):
    • The key diagnostic modality, often sufficient for diagnosis.
    • Shows a "Usual Interstitial Pneumonia" (UIP) pattern:
      • Honeycombing (clustered cystic airspaces).
      • Traction bronchiectasis.
      • Reticular opacities with a subpleural, bibasilar predominance.

⭐ The combination of bibasilar "Velcro-like" crackles and digital clubbing in a patient > 60 years old is highly suggestive of IPF.

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Radiology & Histopathology - Honeycomb Lungs

  • High-Resolution CT (HRCT): Primary imaging modality.

    • Hallmark: Honeycombing (clustered, thick-walled cystic airspaces).
    • Distribution: Predominantly bibasilar and subpleural.
    • Other findings: Reticular opacities, traction bronchiectasis, minimal ground-glass opacities. HRCT of IPF with honeycomb lung and histology
  • Histopathology (Biopsy): Shows Usual Interstitial Pneumonia (UIP) pattern.

    • Key Feature: Temporal heterogeneity (alternating areas of normal lung, inflammation, and dense fibrosis).
    • Microscopic hallmark: Fibroblastic foci (collections of active fibroblasts). UIP Histopathology with Fibroblastic Foci

Exam Favorite: A "definite UIP" pattern on HRCT (bibasilar, subpleural honeycombing) is so specific that a surgical lung biopsy is often not required for diagnosis in the right clinical context.

Management & Prognosis - Slowing the Scarring

  • Antifibrotic Therapy: Goal is to slow Forced Vital Capacity (FVC) decline.
    • Pirfenidone: Inhibits TGF-β, a key mediator of fibrosis.
    • Nintedanib: A tyrosine kinase inhibitor targeting pro-fibrotic pathways (VEGFR, FGFR, PDGFR).
  • Supportive & Symptomatic Care:
    • Supplemental O₂ for hypoxemia (maintain SaO₂ >88%).
    • Pulmonary rehabilitation to improve dyspnea and quality of life.
    • Vaccinations (influenza, pneumococcus).
  • Definitive Treatment:
    • Lung transplantation is the only curative option for eligible candidates.
  • Prognosis:
    • Median survival is 3-5 years post-diagnosis.

Acute exacerbations of IPF are a major cause of mortality, with in-hospital mortality rates often exceeding 50%.

IPF survival with and without antifibrotic treatment

High‑Yield Points - ⚡ Biggest Takeaways

  • Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrosing interstitial pneumonia, mainly in males >60.
  • Presents with gradual dyspnea on exertion and a persistent non-productive cough.
  • Classic physical finding: bibasilar inspiratory "Velcro-like" crackles.
  • HRCT is key for diagnosis, showing a UIP pattern with bibasilar, subpleural honeycombing.
  • PFTs show a restrictive pattern (↓ FVC, normal/↑ FEV1/FVC ratio) and severely ↓ DLCO.
  • Pirfenidone and nintedanib slow disease progression; lung transplant is the only definitive cure.

Practice Questions: Idiopathic pulmonary fibrosis

Test your understanding with these related questions

A 57-year-old man comes to the physician because of a 2-month history of worsening shortness of breath with walking. He has not had any cough, fevers, or recent weight loss. He has hypercholesterolemia, for which he takes simvastatin, but otherwise is healthy. For 35 years he has worked for a demolition company. He has smoked 1 pack of cigarettes daily for the past 33 years. Pulmonary examination shows fine bibasilar end-expiratory crackles. An x-ray of the chest shows diffuse bilateral infiltrates predominantly in the lower lobes and bilateral calcified pleural plaques. The patient is most likely to develop which of the following conditions?

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Flashcards: Idiopathic pulmonary fibrosis

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What is the treatment for idiopathic pulmonary fibrosis? _____

TAP TO REVEAL ANSWER

What is the treatment for idiopathic pulmonary fibrosis? _____

Lung transplant

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