308.3 🏥 內科專科考前版

308.3.1 Mechanistic Deep Dive

308.3.1.1 Vicious Cycle of Bronchiectasis

1. Initial insult (infection, immune defect)
2. Impaired mucociliary clearance
3. Bacterial colonization
4. Persistent inflammation
5. Tissue damage → bronchial wall destruction
6. Permanent dilation
7. Repeat

• Cole’s hypothesis (1986)

308.3.1.2 Neutrophilic Inflammation

• Predominant in bronchiectasis
• Neutrophil elastase + serine proteases damage tissue
• Brensocatib targets this pathway
• IL-8, IL-17 cytokines

308.3.1.3 Pseudomonas Biofilm

• Difficult to eradicate
• Quorum sensing
• Mucoid conversion
• Resistance development
• Chronic suppression strategy

308.3.2 Recent Trials & Updates

308.3.2.1 ASPEN (2024) — Brensocatib

• Phase 3 in bronchiectasis
• ↓ Annual exacerbation rate
• Disease-modifying first in class
• FDA priority review expected

308.3.2.2 TARGET (2024) — Itepekimab

• Anti-IL-33 in bronchiectasis
• Phase 2 promising

308.3.2.3 CONVERGE (2023) — Lefamulin

• Bronchiectasis exacerbations
• Pleuromutilin antibiotic

308.3.2.4 CONTRACTOR Trial Updates

• Inhaled tobramycin in Pseudomonas-positive bronchiectasis
• Improved outcomes

308.3.2.5 2024 ERS/ATS Bronchiectasis Guidelines Update

• Etiology workup standard
• Stepwise treatment
• Newer biologics integration

308.3.3 High-Yield Specialist Points

308.3.3.1 Etiology Workup Algorithm

1. Detailed history (childhood, immune, autoimmune, exposure)
2. CBC + immunoglobulins + IgE
3. Sputum cultures (routine + AFB + fungal)
4. HRCT pattern analysis
5. CFTR testing if suspicious
6. PCD testing if suspicious
7. ANCA + RF + autoimmune
8. Bronchoscopy if focal

308.3.3.2 Phenotype-Based Therapy

• Frequent exacerbator (≥ 3/year): chronic azithromycin
• Pseudomonas-colonized: inhaled antibiotics
• Eosinophilic: consider ICS or biologic
• Brensocatib emerging for neutrophilic phenotype

308.3.3.3 Lady Windermere Syndrome

• Elderly thin women (often post-menopausal)
• Right middle lobe + lingula
• MAC infection
• Tendency to suppress cough
• Treatment same as other MAC

308.3.3.4 Hot Tub Lung vs MAC Pulmonary Disease

• Hot tub: hypersensitivity (Ch305)
• MAC infection: chronic granulomatous + bronchiectasis
• Different management

308.3.3.5 Massive Hemoptysis in Bronchiectasis

• Risk in saccular form
• Treatment:
  • Bronchoscopy
  • Bronchial artery embolization (definitive for most)
  • Surgical resection (focal)
  • Tranexamic acid (acute)

308.3.3.6 Lung Transplantation

• For severe diffuse + functional decline
• BODE-like scoring
• CF more often than non-CF bronchiectasis
• 5-year survival ~ 60-70%

308.3.3.7 Vaccinations

• Influenza annually
• Pneumococcal (PCV20 or PCV15 + PPSV23)
• COVID-19
• Pertussis (Tdap)
• RSV (newly approved, expanding)

308.3.3.8 Pulmonary Rehabilitation

• Beneficial in symptomatic bronchiectasis
• Improves exercise tolerance + QOL
• Often underutilized

308.3.3.9 NTM Pulmonary Disease Pearls

• Increasing incidence (US, Asia, Europe)
• M. avium complex (MAC) most common
• M. abscessus most difficult
• Long-term therapy (12+ months)
• Frequent side effects
• Specialty referral

308.3.3.10 M. abscessus Therapy

• 3-4 IV drugs initial phase (amikacin, imipenem, tigecycline, cefoxitin)
• Oral phase (clofazimine, macrolide, others)
• Surgery for localized disease
• Long-term: ≥ 12 months after culture conversion
• Bedaquiline emerging

308.3.4 Pearls

• Bronchiectasis = permanent bronchial dilation + chronic inflammation
• Etiology workup essential — affects management
• HRCT signs: tram tracks, signet ring, mucus plugging
• Common organisms: H. influenzae, Pseudomonas, S. aureus, NTM
• Treatment pillars: airway clearance + antibiotics + treat underlying
• Azithromycin chronic: EMBRACE, BAT, BLESS — reduces exacerbations
• Brensocatib (ASPEN 2024): first disease-modifying for bronchiectasis
• NTM (MAC): macrolide + ethambutol + rifampin × 12 mo after culture conversion
• Pseudomonas: marker of severity; inhaled tobramycin/colistin

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