307.3 🏥 內科專科考前版

307.3.1 Mechanistic Deep Dive

307.3.1.1 Silica Pathobiology

  • Crystalline silica binds to scavenger receptors
  • Macrophage activation + apoptosis
  • ROS + cytokines (IL-1, TNF)
  • Inflammasome activation
  • Fibrosis cascade

307.3.1.2 Asbestos Carcinogenicity

  • Fiber types: chrysotile (less carcinogenic), amphibole (highly carcinogenic)
  • Long, thin fibers most dangerous
  • ROS, chromosomal damage
  • p53, NF2 mutations in mesothelioma
  • Inflammation + fibrosis

307.3.1.3 PM2.5 Mechanism

  • Penetrates alveoli + systemic circulation
  • Endothelial dysfunction
  • Inflammatory response
  • Oxidative stress
  • Atherosclerosis acceleration

307.3.2 Recent Trials & Updates

307.3.2.1 CheckMate 743 (2021)

  • Nivolumab + ipilimumab vs chemotherapy in mesothelioma
  • ↑ OS in non-epithelioid subtypes especially
  • First-line for unresectable

307.3.2.2 EVALI Updates (2019-2024)

  • Vitamin E acetate primary causative
  • THC products implicated
  • Many cases resolved with cessation + steroids
  • Long-term effects studying

307.3.2.3 Engineered Stone Silicosis Reports

  • Israel, Australia, US, Spain
  • Young workers (20s-40s)
  • Rapid progression
  • Higher mortality than classical
  • OSHA + WHO global response

307.3.2.4 Mesothelioma Combination Trials

  • VEGF + chemotherapy
  • BAP1 mutation targeting
  • Personalized approaches

307.3.3 High-Yield Specialist Points

307.3.3.1 Surgical Lung Biopsy in Pneumoconiosis

  • Usually not needed (history + imaging)
  • Performed when uncertain dx
  • Cryobiopsy alternative
  • Identifies birefringent material

307.3.3.2 Pleural Plaques

  • Marker of asbestos exposure
  • Not symptomatic alone
  • Indicate need for cancer surveillance
  • Lung cancer + mesothelioma risk

307.3.3.3 Mesothelioma Subtypes

  • Epithelioid (60%): better prognosis
  • Sarcomatoid (10%): worse prognosis
  • Biphasic (30%): mixed
  • Immunohistochemistry: calretinin, WT-1, mesothelin

307.3.3.4 Asbestos Exposure Categories

  • Direct (mining, manufacturing)
  • Para-occupational (family of workers)
  • Environmental (near mines, naturally occurring)
  • Latency 20-40 years

307.3.3.5 Engineered Stone Workers’ Profile

  • Young (20s-40s)
  • Multi-ethnic (often Hispanic in US)
  • Years of exposure (often 5-10 years)
  • Rapid progression to PMF
  • Lung transplant common
  • Mortality high

307.3.3.6 Radon Mitigation

  • Sub-slab depressurization
  • Ventilation
  • Mitigation contractors
  • < 2 pCi/L target
  • Mandatory testing in some jurisdictions

307.3.3.7 Indoor Air Quality

  • Smoking cessation
  • Improving ventilation
  • Improved cooking stoves (developing world)
  • Mold remediation
  • Air purifiers (HEPA + carbon)

307.3.3.8 COVID-19 + Air Pollution

  • Higher mortality in polluted areas
  • Mechanism: existing lung disease, immune dysregulation
  • Combined effect significant

307.3.3.9 Climate Change + Respiratory

  • Wildfire smoke increasing
  • Ozone production
  • Allergen season extending
  • Heat-related respiratory exacerbations

307.3.3.10 Workers’ Compensation

  • Documenting exposure
  • Latency considerations
  • Multi-jurisdictional issues
  • Legal support for affected workers

307.3.4 Pearls

  • Silicosis: engineered stone resurgent epidemic; TB risk ↑↑; upper lobe nodules + eggshell LN
  • Asbestosis: pleural plaques + basilar fibrosis; mesothelioma + multiplicative lung cancer; nivolumab + ipi
  • CWP: simple → complicated PMF; Caplan + RA
  • Berylliosis: granulomatous + HLA-DPB1; BeLPT
  • Mesothelioma: CheckMate 743 nivolumab + ipilimumab first-line
  • PM2.5: established CV risk factor; 6% ↑ mortality per 10 ÎŒg/m³
  • Radon: 2nd cause of lung cancer
  • EVALI: vitamin E acetate THC products
  • Engineered stone: rapid progression; younger workers