310.3 🏥 內科專科考前版

310.3.1 Mechanistic Deep Dive

310.3.1.1 IPF Pathogenesis

  • Repetitive epithelial injury (smoking, GERD, environmental)
  • Aberrant wound healing
  • Fibroblast proliferation
  • Collagen + ECM deposition
  • Genetic susceptibility: MUC5B promoter, TERT, SFTPC, MUC2

310.3.1.2 UIP Pattern Histology

  • Spatial + temporal heterogeneity
  • Fibroblast foci
  • Honeycombing
  • Architectural distortion
  • Subpleural / paraseptal predominance

310.3.1.3 Antifibrotic Mechanism

  • Pirfenidone: anti-TGF-β + anti-inflammatory + antioxidant
  • Nintedanib: tyrosine kinase inhibitor (PDGF, FGF, VEGF)
  • Both slow FVC decline ~ 50%

310.3.2 Recent Trials & Updates

310.3.2.1 INBUILD (2019) — Nintedanib for Progressive Pulmonary Fibrosis

  • N = 663 non-IPF progressive fibrotic ILD
  • Nintedanib slowed FVC decline
  • Established treatment for PPF any cause
  • 2020 FDA approval for PPF

310.3.2.2 SENSCIS (2019) — Scleroderma-ILD

  • Nintedanib for SSc-ILD
  • Slowed FVC decline
  • Often combined with MMF
  • 2020 FDA approval for SSc-ILD

310.3.2.3 Anti-MDA5 + Rapidly Progressive ILD

  • Severe phenotype
  • Treatment: aggressive immunosuppression (cyclophosphamide + rituximab + tofacitinib + plasmapheresis)
  • High mortality

310.3.2.4 TRAIL1 (2024) — Pamrevlumab

  • Anti-CTGF antibody
  • Phase 3 for IPF
  • Mixed results; not approved

310.3.2.5 INMARK + INSTAGE — Nintedanib in Early IPF / Combination

  • Combination strategies
  • Earlier treatment

310.3.2.6 Sirolimus in LAM (MILES, 2011 + follow-up)

  • Stabilizes FEV1 decline
  • Continued use needed
  • Approved for LAM

310.3.3 High-Yield Specialist Points

310.3.3.1 MUC5B Polymorphism in IPF

  • rs35705950
  • 30% of population carrier
  • Most common genetic risk factor
  • Associated with longer survival paradoxically

310.3.3.2 Cryobiopsy vs Surgical Biopsy

  • Cryobiopsy: 80%+ diagnostic yield, ↓ mortality
  • Surgical: gold standard, ↑ tissue volume, ↑ morbidity
  • MDD often integrates without biopsy

310.3.3.3 Antifibrotic in Combination

  • Combination not standard
  • Trials testing
  • Single-agent at maximum dose preferred

310.3.3.4 GERD + IPF

  • Common comorbidity
  • Microaspiration may worsen
  • PPI / fundoplication
  • 2024 ATS guidelines mixed evidence

310.3.3.5 Pulmonary Hypertension + ILD

  • Common (Group 3 PH)
  • Worsens outcomes
  • INCREASE trial: inhaled treprostinil
  • Specialty referral

310.3.3.6 Acute Exacerbation IPF

  • < 30 days new dyspnea
  • New ground-glass on HRCT
  • Exclude infection, HF, PE
  • Treatment: high-dose steroids (debated), supportive
  • 50%+ 30-day mortality

310.3.3.7 Lung Transplant Referral Timing

  • FVC < 50% predicted OR
  • DLCO < 35% predicted OR
  • Hospitalization for exacerbation OR
  • Progressive decline despite antifibrotic
  • Earlier referral important (organ wait times)

310.3.3.8 Anti-Synthetase Syndrome

  • Anti-Jo-1, PL-7, PL-12 antibodies
  • ILD + mechanic’s hands + arthritis + Raynaud + fever
  • Often presents with ILD
  • Aggressive IS

310.3.3.9 Vasculitis + Pulmonary Hemorrhage

  • Goodpasture (anti-GBM)
  • ANCA-associated (GPA, MPA)
  • Plasmapheresis + steroids + cyclophosphamide / rituximab

310.3.3.10 Drug-Induced ILD Severity

  • Amiodarone: usually requires high-dose + months
  • ICI: spectrum mild → severe (Class IIa)
  • Methotrexate: hypersensitivity pattern
  • ICI rechallenge: limited data; case-by-case

310.3.4 Pearls

  • ILD: 200+ disorders; classified by 2013 ATS/ERS framework
  • IPF: UIP pattern, worst prognosis; antifibrotic standard
  • INBUILD: nintedanib for progressive pulmonary fibrosis any cause
  • NSIP: better prognosis, CTD-associated, immunosuppressive
  • COP: migratory consolidation, dramatic steroid response
  • Sarcoidosis: non-caseating granulomas, BAL CD4/CD8 > 4
  • MDD: gold standard for ILD diagnosis
  • LAM: women + TSC association + sirolimus
  • PAP: anti-GM-CSF + crazy paving + whole lung lavage
  • Lung transplant: for end-stage; early referral