311.3 🏥 內科專科考前版

311.3.1 Mechanistic Deep Dive

311.3.1.1 Telomere Biology in IPF

  • TERT, TERC, RTEL1 mutations
  • Short telomeres common in IPF
  • Familial IPF often
  • Genetic testing for selected families
  • Influences transplant decision

311.3.1.2 MUC5B Polymorphism

  • rs35705950 promoter
  • Increases mucin secretion
  • 30% of population carrier
  • Strong risk factor for IPF
  • Paradoxically better survival

311.3.1.3 Antifibrotic Combination

  • Pirfenidone + nintedanib not standard
  • Small studies modest benefit
  • Higher side effects
  • Single-agent at max dose first

311.3.2 Recent Trials & Updates

311.3.2.1 CAPACITY (2011) + ASCEND (2014) — Pirfenidone

  • Reduced FVC decline
  • FDA approval 2014

311.3.2.2 INPULSIS-1 + 2 (2014) — Nintedanib

  • Reduced FVC decline
  • FDA approval 2014

311.3.2.3 INBUILD (2019) — Progressive Pulmonary Fibrosis

  • Nintedanib for non-IPF PPF (HP, sarcoid, RA-ILD, etc.)
  • FDA approval 2020 for PPF any cause
  • Game-changer

311.3.2.4 SENSCIS (2019) — Scleroderma-ILD

  • Nintedanib for SSc-ILD
  • FDA approval 2020 for SSc-ILD

311.3.2.5 TRAIL1 (2024) — Pamrevlumab (Anti-CTGF)

  • Did not meet primary endpoint in IPF
  • Other indications continued evaluation

311.3.2.6 IPF-PRO Registry

  • Real-world outcomes
  • Long-term antifibrotic data

311.3.2.7 LOTUSS — Pirfenidone in Scleroderma-ILD

  • Pilot data positive

311.3.2.8 Whole Genome Studies in IPF

  • Multiple new loci
  • Polygenic risk scores emerging

311.3.3 High-Yield Specialist Points

311.3.3.1 Cryobiopsy vs Surgical Biopsy

  • Cryobiopsy: lower mortality, similar diagnostic yield
  • Now preferred when biopsy needed
  • Multicenter expertise growing

311.3.3.2 Familial Pulmonary Fibrosis

  • 15-20% of IPF
  • Genetic testing offered
  • Family screening
  • Earlier referral for transplant

311.3.3.3 Anti-Reflux Surgery in IPF

  • Fundoplication for severe GERD + IPF
  • Mixed evidence
  • Selected cases
  • IPFnet GERD trial limited benefit

311.3.3.4 Pulmonary HTN in IPF

  • Group 3 PH
  • ↑ Mortality
  • Sildenafil INSTAGE
  • Inhaled treprostinil (INCREASE) — for ILD-PH
  • Refer to PH expert

311.3.3.5 Lung Transplant Pearls

  • Bilateral preferred
  • BMI < 30 typical
  • Refer at FVC < 70-80% or DLCO < 50%
  • 5-year survival ~ 50%
  • Lung allocation score (LAS)

311.3.3.6 ILD + Cancer Risk

  • IPF: ↑ lung cancer (esp adenocarcinoma)
  • Annual LDCT in selected
  • Treatment challenges

311.3.3.7 Sarcoidosis Refractory

  • Methotrexate first-line steroid-sparing
  • TNF inhibitors (infliximab, adalimumab)
  • JAK inhibitors (tofacitinib, ruxolitinib)
  • Apremilast for cutaneous

311.3.3.8 Cardiac Sarcoidosis

  • High mortality
  • HRS guidelines
  • Steroids + ICD + pacemaker if needed

311.3.3.9 Renal Involvement Sarcoidosis

  • Hypercalcemia (granuloma activated 1α-hydroxylase)
  • Granulomatous nephritis
  • Steroids

311.3.3.10 Antiphospholipid Antibody Syndrome + ILD

  • Catastrophic APS may have ILD
  • Plasmapheresis + anticoagulation

311.3.3.11 Idiopathic Pulmonary Hemosiderosis

  • Recurrent alveolar hemorrhage
  • Iron-laden macrophages (hemosiderin)
  • Pediatric / young adult
  • Steroids + IS

311.3.4 Pearls

  • IPF: UIP pattern, older male, antifibrotic standard
  • INBUILD 2019: nintedanib for PPF any cause
  • NSIP: CTD-associated, better prognosis, IS
  • COP: migratory consolidation, dramatic steroid response
  • PLCH: smokers, bizarre cysts upper lobe, smoking cessation
  • LAM: women + TSC + sirolimus (MILES); avoid estrogen
  • PAP: anti-GM-CSF + crazy paving + whole lung lavage
  • Sarcoidosis: non-caseating granulomas, BAL CD4/CD8 > 4, Löfgren good prognosis
  • Acute exacerbation IPF: 30-day mortality > 50%