305.3 🏥 內科專科考前版

305.3.1 Mechanistic Deep Dive

305.3.1.1 Emphysema Subtypes

  • Centrilobular: smoking-related, apical predominance
  • Panacinar: α1-AT deficiency, basilar
  • Paraseptal: small airway near pleura; bullae formation
  • Cicatricial: scar-related (e.g., post-TB)

305.3.1.2 α1-Antitrypsin Deficiency

  • SERPINA1 mutations
  • PiMM: normal
  • PiMZ: heterozygous, mild deficiency
  • PiZZ: homozygous, severe deficiency (~ 1%)
  • PiSZ: intermediate
  • Liver disease + emphysema combo

305.3.1.3 Cellular Inflammation in COPD

  • CD8+ T cells (vs CD4+ in asthma)
  • Neutrophils + macrophages
  • Eosinophils in subset
  • Less corticosteroid-responsive than asthma

305.3.2 Recent Trials & Updates

305.3.2.1 ETHOS (2020) + KRONOS, IMPACT, TRINITY

  • Triple therapy (ICS-LABA-LAMA) vs dual (LABA-LAMA)
  • ↓ Exacerbations
  • Established triple as standard for frequent exacerbators

305.3.2.2 BOREAS (2023) + NOTUS (2024) — Dupilumab

  • COPD with eosinophilic phenotype + on optimal inhaler therapy
  • Dupilumab ↓ exacerbations
  • Improved FEV1, symptoms
  • FDA approved 2024
  • Game-changing for eosinophilic COPD

305.3.2.3 MATINEE (2024) — Mepolizumab

  • Eosinophilic COPD
  • ↓ Exacerbations
  • Pending FDA approval

305.3.2.4 HOT-HMV (2017)

  • Long-term home NIV for COPD with chronic hypercapnia
  • Reduced exacerbations + hospital readmissions
  • Long-term mortality benefit

305.3.2.5 REACT (2019) — Endobronchial Valves

  • LIBERATE trial: severe emphysema
  • Improved FEV1, QOL
  • For non-collateral ventilation patients

305.3.2.6 Roflumilast (RE2SPOND, REACT)

  • For chronic bronchitis + frequent exacerbations
  • Modest exacerbation reduction
  • Side effects: GI, weight loss, mood

305.3.2.7 Azithromycin (CRADLE, COMET)

  • Chronic 250 mg/d or 500 mg 3x/week
  • For frequent exacerbations
  • Caution: QT, resistance

305.3.3 High-Yield Specialist Points

305.3.3.1 Pneumonia Risk with ICS

  • ↑ Pneumonia in COPD on ICS (TORCH, IMPACT)
  • Higher with fluticasone than budesonide
  • Use ICS in COPD with: eosinophilia ≥ 300, frequent exacerbations
  • Avoid ICS in COPD without these features

305.3.3.2 Frequent Exacerbator Phenotype

  • ≥ 2 exacerbations/year
  • Different biology
  • Higher inflammation
  • ICS, triple therapy, azithromycin, roflumilast, biologics

305.3.3.3 Eosinophilic COPD

  • Blood eosinophils ≥ 300: more steroid-responsive
  • 100-299: intermediate response
  • < 100: minimal benefit from ICS
  • Determines therapy selection

305.3.3.4 Cardiovascular Comorbidity

  • ↑ MI, stroke, HF, arrhythmia
  • β-blocker safe in COPD with HF (despite older concerns)
  • Cardio-selective β-blockers (metoprolol, bisoprolol)

305.3.3.5 Lung Cancer Screening in COPD

  • USPSTF: ≥ 20 pack-year + age 50-80 + current/recent smoker
  • LDCT annually
  • COPD ↑ lung cancer risk

305.3.3.6 α1-AT Augmentation Therapy

  • IV infusion of α1-AT protein
  • For PiZZ phenotype with emphysema
  • Weekly infusions
  • Slows progression
  • Specialty referral

305.3.3.7 NETT (National Emphysema Treatment Trial)

  • LVRS for upper-lobe predominant emphysema with low exercise capacity
  • Reduced mortality in select subgroup
  • Reserved for specific phenotype

305.3.3.8 Endobronchial Valve Selection

  • Severe emphysema with hyperinflation
  • Heterogeneous (target lobe)
  • Intact fissure (no collateral ventilation)
  • One-way valves block target lobe → atelectasis → relieves hyperinflation
  • Better than LVRS in many

305.3.3.9 Lung Transplant for COPD

  • BODE score guides
  • Single or bilateral
  • 5-year survival ~ 55%
  • Continued specialty care

305.3.3.10 Pulmonary HTN in COPD

  • Common in severe COPD
  • WHO Group 3
  • Treatment: LTOT, treat underlying
  • PAH-specific drugs not routinely recommended
  • Refer to PH clinic for severe

305.3.3.11 COPD + Diabetes

  • Triple therapy may affect glucose
  • Cardiovascular comorbidity
  • Multidisciplinary management

305.3.3.12 Cachexia + COPD

  • Common in severe disease
  • Predicts mortality
  • Nutrition + pulmonary rehab + exercise

305.3.3.13 Palliative Care in COPD

  • Important late stage
  • Symptom management (dyspnea, anxiety, depression)
  • Goals of care discussions
  • Hospice referral if appropriate

305.3.4 Pearls

  • COPD diagnosis: post-bronchodilator FEV1/FVC < 0.7
  • GOLD ABE 2023: A (low symp + low exac) / B (high symp + low exac) / E (≥ 2 exac or ≥ 1 hosp)
  • Treatment: LABA + LAMA → triple if eosinophilic
  • Biologics 2024: dupilumab (BOREAS/NOTUS), mepolizumab (MATINEE) for eosinophilic
  • Smoking cessation: single most important
  • α1-AT deficiency: PiZZ, basilar emphysema, early onset
  • LTOT: PaO2 ≀ 55; ≥ 15 hr/d
  • Exacerbation: SABA + steroid + antibiotics + NIV if pH < 7.35