305.1 🎓 醫孞生版

305.1.0.1 📌 䞀頁重點

305.1.0.1.1 Definition + Epidemiology
305.1.0.1.1.1 COPD
  • Chronic, progressive, treatable but not fully reversible airflow limitation
  • Combination of emphysema + chronic bronchitis
  • Inflammatory disease with systemic effects
305.1.0.1.1.2 Components
  • Emphysema: alveolar destruction → loss of elastic recoil
  • Chronic bronchitis: clinical (chronic cough + sputum production ≥ 3 months × 2 years); mucus hypersecretion + inflammation in airways
  • Small airway disease: obstruction in bronchioles
305.1.0.1.1.3 Epidemiology
  • 3rd leading cause of death globally
  • ~ 300 million worldwide
  • Underdiagnosed
  • Taiwan: ~ 10% prevalence in > 40 yo
305.1.0.1.1.4 Etiology
  • Tobacco smoking (#1, > 90% of cases in developed)
  • Air pollution (cooking fuel, biomass; major in developing countries)
  • Occupational exposures: dusts, fumes, chemicals
  • Genetic: α1-antitrypsin deficiency (1% — early-onset, basilar, panacinar)
  • Childhood lung development
  • Asthma (some develop COPD)
305.1.0.1.2 Pathophysiology
305.1.0.1.2.1 Inflammation
  • Neutrophils, macrophages, CD8+ T cells
  • Cytokines: TNF-α, IL-6, IL-8
  • Less responsive to corticosteroids than asthma
305.1.0.1.2.2 Tissue Destruction
  • Imbalance of proteases (elastase) and antiproteases (α1-antitrypsin)
  • ROS, oxidative stress
  • Alveolar wall destruction → emphysema
  • Mucus hypersecretion → chronic bronchitis
305.1.0.1.2.3 Physiologic Consequences
  • Airflow limitation (small airway narrowing + emphysema)
  • Hyperinflation (gas trapping)
  • Diffusion impairment (alveolar destruction)
  • V/Q mismatch (hypoxemia)
  • Hypercapnia (severe disease)
  • Pulmonary HTN + cor pulmonale
305.1.0.1.3 Clinical Features
305.1.0.1.3.1 Symptoms
  • Dyspnea (progressive, exertional)
  • Chronic cough (productive in chronic bronchitis)
  • Sputum production (often morning)
  • Wheezing
  • Chest tightness
  • Fatigue, weight loss (cachexia in severe)
305.1.0.1.3.2 Examination
  • Barrel chest (hyperinflation)
  • Pursed-lip breathing
  • Use of accessory muscles
  • Cyanosis
  • Clubbing (rare, suggests alternative diagnosis)
  • Decreased breath sounds
  • Wheezing, rhonchi
  • Prolonged expiration
  • Signs of cor pulmonale (peripheral edema, JVD)
305.1.0.1.4 Diagnosis
305.1.0.1.4.1 Spirometry
  • Post-bronchodilator FEV1/FVC < 0.7 (gold standard)
  • Or < LLN
  • Confirms airflow limitation
305.1.0.1.4.2 Severity by GOLD (FEV1 % Predicted)
  • GOLD 1 (mild): FEV1 ≥ 80%
  • GOLD 2 (moderate): FEV1 50-79%
  • GOLD 3 (severe): FEV1 30-49%
  • GOLD 4 (very severe): FEV1 < 30%
305.1.0.1.4.3 GOLD ABE Group (Updated 2023-2024)
  • A: Low symptoms (mMRC 0-1, CAT < 10) + 0-1 exacerbations no hospitalization
  • B: High symptoms (mMRC ≥ 2, CAT ≥ 10) + 0-1 exacerbations no hospitalization
  • E: ≥ 2 exacerbations OR ≥ 1 hospitalization (regardless of symptoms)
305.1.0.1.4.4 Symptom Assessment Tools
  • mMRC (modified Medical Research Council) dyspnea scale 0-4
  • CAT (COPD Assessment Test) 0-40
  • Exacerbation history
305.1.0.1.4.5 Additional Testing
  • Chest X-ray: hyperinflation, bullae, flattened diaphragm
  • HRCT: emphysema characterization (centrilobular, panlobular, paraseptal), bullae, bronchiectasis
  • DLCO: ↓ in emphysema
  • ABG: hypoxemia, hypercapnia (severe)
  • α1-Antitrypsin level + phenotype: early-onset, basilar emphysema, family history (level < 11 ÎŒM)
  • 6MWT: functional capacity
  • Echo: cor pulmonale, PH
305.1.0.1.5 Treatment — GOLD 2024-2025
305.1.0.1.5.1 Smoking Cessation
  • Single most important intervention
  • ↓ Mortality, slow decline
  • Methods:
    • Counseling
    • Nicotine replacement therapy (NRT): gum, patch, lozenge, inhaler, spray
    • Varenicline: nicotinic receptor partial agonist
    • Bupropion: norepinephrine + dopamine reuptake inhibitor
    • E-cigarettes (debated)
  • 5As / 5Rs counseling approach
305.1.0.1.5.2 Pharmacotherapy

Group A (Low symptoms, low exacerbation): - SABA / SAMA as needed - Consider LABA or LAMA

Group B (High symptoms, low exacerbation): - LABA + LAMA combo (preferred) - Mono: LABA or LAMA

Group E (Frequent exacerbation): - LABA + LAMA initial - If blood eosinophils ≥ 300 OR eosinophils 100-299 with frequent exacerbations: - Triple therapy: ICS + LABA + LAMA - Add roflumilast or azithromycin for chronic bronchitis or frequent exacerbations

305.1.0.1.5.3 Inhaled Medications

LABA (Long-Acting β2-Agonist): - Salmeterol (12h) - Formoterol (12h, fast onset) - Indacaterol (24h) - Vilanterol (24h) - Olodaterol (24h)

LAMA (Long-Acting Muscarinic Antagonist): - Tiotropium (Spiriva, 24h) - Aclidinium (12h) - Umeclidinium (24h) - Glycopyrronium (24h) - Revefenacin (24h)

ICS (Inhaled Corticosteroids): - Budesonide - Fluticasone - Mometasone - Use cautiously: pneumonia risk

Combination Inhalers: - LABA-LAMA: indacaterol-glycopyrronium (Ultibro), olodaterol-tiotropium (Stiolto), umeclidinium-vilanterol (Anoro) - ICS-LABA: fluticasone-salmeterol (Advair), budesonide-formoterol (Symbicort) - Triple (ICS-LABA-LAMA): budesonide-glycopyrronium-formoterol (Breztri), fluticasone-vilanterol-umeclidinium (Trelegy), fluticasone-formoterol-glycopyrronium (Trimbow)

305.1.0.1.5.4 Oral Medications

Roflumilast (PDE4 Inhibitor): - For severe COPD with chronic bronchitis + frequent exacerbations - Reduces exacerbations - Side effects: diarrhea, weight loss, mental health - Class IIa add-on

Azithromycin (Chronic): - For frequent exacerbations despite optimal inhaler therapy - 250 mg/d or 500 mg 3x/week × 6-12 months - Reduces exacerbations - Caution: QT prolongation, hearing loss, antibiotic resistance

Mucolytics: - N-acetylcysteine (NAC) - Erdosteine - Carbocisteine - Modest benefit; may reduce exacerbations

Theophylline: - Older; narrow therapeutic window - Limited current use

305.1.0.1.5.5 Biologics (NEW 2024 — Game-Changer)

Dupilumab (Anti-IL-4Rα): - BOREAS (2023) + NOTUS (2024) trials - For COPD with eosinophilic phenotype (blood eos ≥ 300) - Reduces exacerbations - Improves FEV1 - FDA approved 2024 for COPD with eosinophilic phenotype

Mepolizumab (Anti-IL-5): - MATINEE (2024) trial - For eosinophilic COPD with frequent exacerbations - Reduces exacerbations - Pending FDA approval for COPD

Itepekimab (Anti-IL-33): - Phase 2 promising - Future indication possible

Tezepelumab (Anti-TSLP): - Phase 2 in COPD ongoing

305.1.0.1.5.6 Oxygen Therapy

Long-Term Oxygen Therapy (LTOT): - For chronic hypoxemia - Criteria: - PaO2 ≀ 55 mmHg OR SpO2 ≀ 88% at rest, OR - PaO2 56-59 + cor pulmonale OR polycythemia (HCT > 55%) - ≥ 15 hours/day required for survival benefit - Reduces mortality

Ambulatory Oxygen: - For exercise-induced desaturation - Improves exercise capacity

305.1.0.1.5.7 Non-Invasive Ventilation (NIV)

Indications: - Acute hypercapnic exacerbation with respiratory acidosis (pH < 7.35 with PaCO2 > 45) - Chronic stable hypercapnia with frequent exacerbations (long-term home NIV; HOT-HMV trial) - COPD-OSA overlap

305.1.0.1.5.8 Pulmonary Rehabilitation
  • Class I for COPD with persistent symptoms
  • 6-12 week structured program
  • Improves dyspnea + exercise tolerance + QOL
  • Reduces hospitalizations
305.1.0.1.5.9 Vaccinations
  • Influenza annually
  • Pneumococcal (PCV15/20 + PPSV23)
  • COVID-19
  • Pertussis (Tdap)
  • RSV (recently approved, expanding)
305.1.0.1.5.10 Surgical / Procedural

Lung Volume Reduction Surgery (LVRS): - For severe emphysema with hyperinflation (upper lobe predominant) - NETT trial - Selected patients

Endobronchial Valves: - Less invasive alternative - For severe emphysema - Zephyr, Spiration valves - Improves dyspnea + exercise

Bullectomy: - For large bullae (> 1/3 hemithorax) - Symptomatic improvement

Lung Transplantation: - End-stage disease - BODE score for selection - 5-year survival ~ 55%

305.1.0.1.6 Acute COPD Exacerbation
305.1.0.1.6.1 Definition
  • Acute worsening of respiratory symptoms beyond normal day-to-day variation
  • Often viral or bacterial infection trigger
305.1.0.1.6.2 Triggers
  • Viral infections (most common — rhinovirus, RSV, influenza, COVID-19)
  • Bacterial (H. influenzae, S. pneumoniae, M. catarrhalis, P. aeruginosa)
  • Environmental (smoking, pollution)
  • Non-adherence
  • PE (consider in setting of risk factors)
305.1.0.1.6.3 Severity
  • Mild: ↑ SABA only
  • Moderate: SABA + antibiotics ± steroids
  • Severe: requires hospitalization
305.1.0.1.6.4 Treatment

Bronchodilators: - SABA (albuterol) + SAMA (ipratropium) nebulized

Systemic Steroids: - Prednisone 40 mg/d × 5 days - Reduces relapse, shortens length of stay

Antibiotics: - Indications: 2 of 3 (↑ dyspnea, ↑ sputum, ↑ sputum purulence) OR mechanical ventilation - Common: amoxicillin-clavulanate, azithromycin, doxycycline, cefuroxime - Pseudomonas coverage in severe / repeated hospitalizations: cefepime, piperacillin-tazobactam, fluoroquinolone

Supplemental Oxygen: - Target SpO2 88-92% (avoid hyperoxia → ↑ CO2 retention)

Non-Invasive Ventilation (NIV): - For acute hypercapnic exacerbation (pH < 7.35) - BiPAP / NIPPV - Reduces intubation, mortality

Mechanical Ventilation: - For NIV failure or contraindication - Severe acidosis, altered mental status

Discharge: - Optimize inhaler technique - Vaccinations - Pulmonary rehab - Smoking cessation - Action plan

305.1.0.2 🩺 床邊速查

  • 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)
  • Group A: SABA/SAMA → LABA or LAMA
  • Group B: LABA + LAMA combo
  • Group E: LABA + LAMA → triple if eos ≥ 300 or eos 100-299 + frequent exac
  • Biologics 2024: dupilumab (BOREAS/NOTUS), mepolizumab (MATINEE) for eosinophilic COPD
  • LTOT: PaO2 ≀ 55 or 56-59 + cor pulmonale; ≥ 15 hr/d
  • Exacerbation: SABA + steroids 40 mg × 5 d + antibiotics + NIV if pH < 7.35