308.1 🎓 醫孞生版

308.1.0.1 📌 䞀頁重點

308.1.0.1.1 Definition + Epidemiology
308.1.0.1.1.1 Bronchiectasis
  • Permanent, irreversible dilation of bronchi + chronic inflammation + impaired mucociliary clearance
  • Recurrent infections → progressive destruction
  • Spectrum from focal to diffuse
308.1.0.1.1.2 Epidemiology
  • Increasing recognition (HRCT availability)
  • 50-500 per 100,000 in developed countries
  • Higher in elderly, women, lower income
  • ↑ With imaging access; not just developing countries
308.1.0.1.2 Etiology
308.1.0.1.2.1 Non-CF Bronchiectasis Causes

Post-Infectious (~ 30%): - Childhood pneumonia (viral, bacterial) - Tuberculosis - Non-tuberculous mycobacteria (MAC, M. abscessus) - Pertussis - Measles - Adenovirus

Immunodeficiency (~ 10%): - CVID (common variable immunodeficiency) - IgA deficiency - Hypogammaglobulinemia - HIV - Specific antibody deficiency

ABPA (allergic bronchopulmonary aspergillosis): - Asthma or CF + Aspergillus - See Ch305

Connective Tissue Disease: - Rheumatoid arthritis (most common) - SLE, Sjögren, scleroderma

Inflammatory Bowel Disease: - Ulcerative colitis > Crohn’s - ~ 5% of IBD

Genetic / Congenital: - Cystic fibrosis (separate entity, Ch308) - Primary ciliary dyskinesia (PCD) / Kartagener syndrome (PCD + situs inversus + sinusitis + bronchiectasis) - Young’s syndrome (azoospermia + sinusitis + bronchiectasis) - α1-antitrypsin deficiency - Williams-Campbell syndrome (cartilage deficiency) - Mounier-Kuhn (tracheobronchomegaly)

Aspiration: - Recurrent - GERD - Esophageal motility disorders

Other: - Yellow nail syndrome - Diffuse panbronchiolitis (Asian populations) - Idiopathic (up to 50% in some studies)

308.1.0.1.3 Clinical Features
308.1.0.1.3.1 Symptoms
  • Chronic productive cough (most common; usually large volume sputum)
  • Hemoptysis (50% lifetime; some massive)
  • Recurrent respiratory infections
  • Dyspnea
  • Fatigue
  • Wheezing
  • Halitosis
  • Sinus symptoms (if PCD or CF)
  • Weight loss
308.1.0.1.3.2 Acute Exacerbations
  • ↑ Sputum volume + purulence
  • ↑ Dyspnea
  • Fever, malaise
  • ↓ Lung function
308.1.0.1.3.3 Examination
  • Crackles (especially basilar, persistent)
  • Wheezes (some)
  • Clubbing (~ 10-30%)
  • Signs of underlying disease
308.1.0.1.4 Diagnosis
308.1.0.1.4.1 HRCT (Gold Standard)
  • Tram tracks / parallel lines (dilated airways)
  • Signet ring sign (bronchus > accompanying artery)
  • Cluster of cysts
  • Bronchial wall thickening
  • Mucus plugging (“finger-in-glove”)
  • Patterns:
    • Cylindrical (mild, uniform dilation)
    • Varicose (irregular dilation)
    • Cystic / saccular (severe, cyst-like)
308.1.0.1.4.2 Etiology Workup (CRITICAL for management)

Initial: - CBC + differential - Serum immunoglobulins (IgA, IgG, IgM) - Specific antibody response (post-vaccine titers) - HIV testing - α1-antitrypsin level + phenotype - CF testing (sweat chloride, CFTR genetic testing in select adults) - ANCA, RF, anti-CCP, ANA, dsDNA (autoimmune) - IgE + Aspergillus (ABPA workup)

Sputum: - Routine culture - AFB (TB + NTM) - Fungal - Gram stain

Additional: - PCD testing (nasal NO, ciliary biopsy, genetic — DNAH5, DNAH11, etc.) - Bronchoscopy if focal disease - Cardiac echo - HIV testing - Pulmonary function tests

308.1.0.1.4.3 Pulmonary Function
  • Obstructive pattern most common
  • Variable severity
  • DLCO often normal
308.1.0.1.5 Microbiology
308.1.0.1.5.1 Common Organisms (Chronic Infection)
  • Haemophilus influenzae (~ 30%)
  • Pseudomonas aeruginosa (~ 30%) — predicts worse outcomes
  • Staphylococcus aureus
  • Streptococcus pneumoniae
  • Moraxella catarrhalis
  • Non-tuberculous mycobacteria (NTM) — increasingly recognized
  • Aspergillus (ABPA in some)
308.1.0.1.5.2 Pseudomonas Significance
  • Marker of severe disease
  • ↑ Exacerbations
  • ↑ Decline in lung function
  • ↑ Mortality
  • Inhaled antibiotics + chronic suppression
308.1.0.1.6 Treatment
308.1.0.1.6.1 Multi-Pillar Approach

1. Airway Clearance - Chest physiotherapy (postural drainage) - Oscillatory positive expiratory pressure (OPEP): Acapella, Flutter - High-frequency chest wall oscillation (HFCWO): vest - Hypertonic saline (7% NaCl) nebulized: improves mucus clearance - Mannitol (less common) - Active cycle of breathing techniques

2. Treat Underlying Disease - IgG replacement (CVID) - ART (HIV) - Treat ABPA (steroids + itraconazole + dupilumab refractory) - Treat NTM - RA management - CF-specific (Ch308)

3. Antibiotics

Acute Exacerbations: - Cover known colonizers - Amoxicillin-clavulanate, azithromycin, doxycycline - Pseudomonas: ciprofloxacin, IV cefepime/pip-tazo

Chronic Suppressive: - Azithromycin 250 mg/d or 500 mg 3x/week (EMBRACE, BAT, BLESS trials) - Reduces exacerbations 50% - Caution: QT, hearing, antibiotic resistance - Inhaled tobramycin (Pseudomonas): TOBI, Bethkis - Inhaled colistin: refractory Pseudomonas - Inhaled aztreonam: AIR-BX, EMBRACE-CF (CF mainly)

4. Bronchodilators - SABA / LABA for symptomatic - Variable benefit in non-CF bronchiectasis - LAMA option

5. Inhaled Steroids - For coexisting asthma or eosinophilic inflammation - Not routine for non-CF bronchiectasis

6. Biologics + New Therapies

Brensocatib (DPP-1 Inhibitor) — NEW 2024 - ASPEN trial (2024 positive) - Reduces neutrophil serine proteases - ↓ Exacerbation rate - First disease-modifying for bronchiectasis - Expected FDA approval 2024-2025

Itepekimab (anti-IL-33): - Phase 2 in bronchiectasis - Targets upstream inflammation

Anti-IL-5 / IL-5R: - For eosinophilic phenotype (some) - Trials ongoing

7. Surgical Resection - For localized severe disease - Massive hemoptysis source - Recurrent infections in one lobe - VATS or open

8. Lung Transplantation - For end-stage diffuse bronchiectasis - CF more often - Outcomes good in select

308.1.0.1.7 Special Populations
308.1.0.1.7.1 Primary Ciliary Dyskinesia (PCD) / Kartagener
  • Genetic defect in ciliary function
  • Bronchiectasis + sinusitis + situs inversus (Kartagener)
  • Infertility
  • Diagnosis: low nasal NO, ciliary EM/genetic
  • Treatment: similar to CF (airway clearance, antibiotics)
308.1.0.1.7.2 Diffuse Panbronchiolitis (DPB)
  • Asian populations (Japan, Korea, China)
  • Bronchioles + sinuses
  • Erythromycin (low-dose, long-term) dramatically effective
  • HLA-Bw54 association
308.1.0.1.7.3 Mounier-Kuhn (Tracheobronchomegaly)
  • Idiopathic tracheal + bronchial dilation
  • Adults
  • Treatment: airway clearance + antibiotics
  • Stenting for severe
308.1.0.1.8 NTM (Non-Tuberculous Mycobacteria)
308.1.0.1.8.1 Common Species
  • Mycobacterium avium complex (MAC) — most common
  • Mycobacterium abscessus — more difficult to treat
  • Mycobacterium kansasii
  • Mycobacterium xenopi
308.1.0.1.8.2 Risk Factors
  • Bronchiectasis (predisposes)
  • Elderly women (“Lady Windermere syndrome”: tall, thin women with right middle lobe + lingula bronchiectasis)
  • Tap water exposure (esp showerheads)
  • Soil
308.1.0.1.8.3 Diagnosis (ATS/IDSA Criteria)
  • Clinical + radiographic + microbiologic
  • 2 sputum positive + radiographic findings OR 1 BAL positive
  • Lung biopsy + culture (rare)
308.1.0.1.8.4 Treatment
  • MAC: macrolide (azithromycin) + ethambutol + rifampin × 12 months after culture conversion
  • M. abscessus: complex, multi-drug (often 3-4 agents) IV phase + oral phase × 12 months minimum
  • Inhaled amikacin for refractory MAC
  • Long-duration therapy
  • Specialty referral

308.1.0.2 🩺 床邊速查

  • Bronchiectasis: permanent bronchial dilation + chronic infection + inflammation
  • HRCT signs: tram tracks, signet ring, bronchial wall thickening
  • Common organisms: H. influenzae, Pseudomonas, S. aureus, NTM
  • Etiology workup: immunoglobulins, CFTR, ANCA, RF, IgE, NTM, PCD if suspicious
  • Treatment pillars: airway clearance + antibiotics + treat underlying + new biologics (brensocatib)
  • Azithromycin chronic for frequent exacerbations
  • Brensocatib (ASPEN 2024) = first disease-modifying for bronchiectasis
  • MAC (“Lady Windermere”): macrolide + ethambutol + rifampin × 12 mo after culture conversion