304.1 🎓 醫孞生版

304.1.0.1 📌 䞀頁重點

304.1.0.1.1 Definition + Epidemiology
304.1.0.1.1.1 Asthma
  • Chronic airway inflammation + bronchial hyperresponsiveness + variable airflow limitation
  • Reversible airflow obstruction (key distinguishing from COPD)
  • Heterogeneous condition
304.1.0.1.1.2 Epidemiology
  • ~ 300 million worldwide
  • Most common chronic disease in children
  • Increasing prevalence in industrialized countries
  • Taiwan: 5-10% prevalence in children, 3-5% in adults
304.1.0.1.1.3 Risk Factors
  • Genetic: familial, polygenic
  • Atopy: allergic rhinitis, eczema, food allergy (“atopic march”)
  • Environmental: tobacco smoke, pollution, allergens (dust mites, pollen, pets), occupational
  • Viral infections (RSV, rhinovirus in childhood)
  • Obesity (associated)
304.1.0.1.2 Pathophysiology
304.1.0.1.2.1 Type 2 (T2) High Inflammation
  • Th2 cells, ILC2s
  • IL-4, IL-5, IL-13
  • Eosinophils prominent
  • Allergic + non-allergic eosinophilic
  • Responsive to ICS + biologics
304.1.0.1.2.2 Type 2 (T2) Low Inflammation
  • Th17 / neutrophilic
  • Non-allergic
  • Less ICS-responsive
  • Resistant to traditional therapies
  • Newer biologic (tezepelumab) for some
304.1.0.1.2.3 Asthma Phenotypes (Clinical)
  • Allergic asthma: childhood onset, atopy, ↑ IgE
  • Non-allergic eosinophilic: adult onset, no allergy
  • AERD (aspirin-exacerbated respiratory disease): nasal polyps + asthma + aspirin sensitivity
  • Exercise-induced bronchoconstriction (EIB): triggered by exercise
  • Cough-variant asthma: cough as primary symptom
  • Occupational asthma: workplace exposure
  • Pre-menstrual asthma: hormonal
304.1.0.1.3 Clinical Features
304.1.0.1.3.1 Symptoms
  • Wheezing (most common)
  • Cough (especially nocturnal or with exercise)
  • Dyspnea
  • Chest tightness
  • Variable + recurrent
304.1.0.1.3.2 Triggers
  • Allergens (pollens, dust mites, animal dander, mold)
  • Viral infections
  • Tobacco smoke
  • Cold air
  • Exercise
  • Stress
  • Strong odors
  • Medications (NSAIDs, β-blockers)
  • Occupational exposures
304.1.0.1.3.3 Examination
  • Wheezing (especially expiratory)
  • Prolonged expiration
  • Use of accessory muscles (severe)
  • Cyanosis (severe)
  • Silent chest (life-threatening — no movement of air)
  • Hyperresonance to percussion
  • Tachycardia, tachypnea
  • Pulsus paradoxus (severe)
304.1.0.1.4 Diagnosis
304.1.0.1.4.1 Spirometry + Bronchodilator Reversibility
  • FEV1/FVC < 0.7 at baseline (or < LLN)
  • Reversibility: > 12% AND > 200 mL improvement in FEV1 after bronchodilator
  • Diagnostic of obstructive + reversible airway disease
304.1.0.1.4.2 Methacholine Challenge
  • For normal spirometry with suspicion
  • Positive: PC20 ≀ 8 mg/mL (FEV1 drops > 20% at concentration ≀ 8)
  • High sensitivity
304.1.0.1.4.3 Peak Expiratory Flow (PEF)
  • Variability > 20% between AM and PM
  • Useful for monitoring
304.1.0.1.4.4 Other Tests
  • FeNO (fractional exhaled nitric oxide)
    • < 25 ppb: low T2 inflammation
    • 25-50: intermediate

    • 50: high T2 inflammation

  • Blood eosinophils (> 150-300 cells/ÎŒL — biologic response predictor)
  • Total IgE + specific IgE (allergic)
  • Skin prick test (allergens)
  • Chest X-ray to rule out alternative
304.1.0.1.5 Severity Assessment
304.1.0.1.5.1 Asthma Control
  • Symptoms frequency (daytime, nocturnal)
  • Reliever use
  • Activity limitation
  • Lung function

ACT (Asthma Control Test) Score: - 25: well-controlled - 20-24: partially controlled - < 20: poorly controlled

304.1.0.1.5.2 Asthma Severity
  • Mild intermittent: symptoms ≀ 2/week
  • Mild persistent: symptoms > 2/week
  • Moderate persistent: daily symptoms
  • Severe persistent: throughout day
  • Severe (uncontrolled despite high-dose ICS + LABA): refers to biologic consideration
304.1.0.1.6 Treatment — GINA 2024 + 2025
304.1.0.1.6.1 Treatment Track 1 (Preferred, Adults + Adolescents)

As-Needed ICS-Formoterol = key innovation - All asthma severities should have ICS-containing reliever - No more SABA-only reliever (changes from older guidelines)

Stepwise Approach: - Step 1: as-needed low-dose ICS-formoterol - Step 2: as-needed low-dose ICS-formoterol - Step 3: maintenance low-dose ICS-formoterol + as-needed - Step 4: maintenance medium-dose ICS-formoterol + as-needed - Step 5: high-dose ICS-LABA + add-on (LAMA, biologic, OCS)

304.1.0.1.6.2 Treatment Track 2 (Alternative)
  • Maintenance + as-needed SABA reliever
  • Less preferred (now considered inferior)
304.1.0.1.6.3 Medications

Inhaled Corticosteroids (ICS) — Cornerstone - Budesonide - Fluticasone - Beclomethasone - Mometasone - Ciclesonide - Reduces exacerbations + symptoms + airway inflammation

LABA (Long-Acting β-Agonist) - Salmeterol - Formoterol (also has fast onset) - Indacaterol (24h) - Always combined with ICS (LABA monotherapy unsafe)

Combination ICS-LABA - Budesonide-formoterol (Symbicort) - Fluticasone-salmeterol (Advair) - Fluticasone-vilanterol (Breo) - Beclomethasone-formoterol (Foster) - Mometasone-formoterol (Dulera)

SABA (Short-Acting β-Agonist) - Albuterol (salbutamol) - Levalbuterol - Old reliever; now ICS-formoterol preferred

LAMA (Long-Acting Muscarinic Antagonist) - Tiotropium (Spiriva) - Add-on for severe asthma - Bronchodilator + anti-inflammatory effects

Leukotriene Modifiers - Montelukast (LTRA) - Zafirlukast - Useful for AERD, EIB, allergic asthma - FDA boxed warning: psychiatric effects (2020)

Oral Corticosteroids - Prednisone for exacerbations - Short-term high-dose - Chronic use to minimize (side effects)

Theophylline - Older - Narrow therapeutic window - Limited use

Biologics (See below)

304.1.0.1.6.4 Biologics (Severe Asthma)

Anti-IgE: Omalizumab - For severe allergic asthma + ↑ IgE - SC every 2-4 weeks - Reduces exacerbations - Chronic urticaria also indication

Anti-IL-5: Mepolizumab + Reslizumab - For severe eosinophilic asthma (blood eos > 150-300) - SC monthly - Reduces exacerbations + reduces OCS use

Anti-IL-5R: Benralizumab - SC q4 weeks initially, then q8 weeks - Depletes eosinophils - Severe eosinophilic asthma

Anti-IL-4/IL-13: Dupilumab - SC q2 weeks - Targets IL-4Rα (shared by IL-4 and IL-13) - Severe T2-high asthma (eosinophils, FeNO) - Also for atopic dermatitis, CRSwNP, EoE

Anti-TSLP: Tezepelumab (2022, NEW) - SC monthly - Targets upstream alarmin - Effective in both T2-high AND T2-low (broader than other biologics) - For severe asthma regardless of eosinophil count

304.1.0.1.6.5 Selecting Biologic
  • Eosinophils > 300, ↑ FeNO: dupilumab (T2-high)
  • Eosinophils > 150, exacerbations on ICS-LABA: anti-IL-5 (mepo, reslizumab, benra)
  • High IgE, perennial allergen: omalizumab
  • All severities, T2-high or low: tezepelumab
  • AERD/CRSwNP: dupilumab
304.1.0.1.6.6 Step-Down Therapy
  • Once asthma controlled 3 months
  • Reduce in stepwise fashion
  • Maintain on lowest effective therapy
  • ICS continues at minimum
304.1.0.1.6.7 Patient Education
  • Inhaler technique (critical, often suboptimal)
  • Spacer use
  • Trigger avoidance
  • Action plan
  • Self-monitoring (PEF, symptoms)
  • When to seek emergency care
304.1.0.1.7 Acute Asthma Exacerbation
304.1.0.1.7.1 Triggers
  • Viral infection (#1)
  • Allergen exposure
  • Medication non-compliance
  • Environmental (smoke, pollution)
304.1.0.1.7.2 Severity Assessment
  • Mild-moderate: dyspnea on exertion, PEF > 50% predicted, SpO2 > 90%
  • Severe: dyspnea at rest, PEF 30-50%, SpO2 90-95%
  • Life-threatening:
    • Silent chest
    • Cyanosis
    • Confusion
    • Bradycardia
    • SpO2 < 90%
    • PEF < 30%
  • Near-fatal:
    • Mechanical ventilation
    • Cardiac arrest
304.1.0.1.7.3 Treatment
  • Oxygen (target SpO2 93-95% adults; 94-98% pediatric)
  • SABA (albuterol) nebulized continuous or q20 min
  • Ipratropium (LAMA) nebulized (synergistic)
  • Systemic corticosteroids (prednisone 40-50 mg PO or methylpred 60-125 mg IV)
  • Magnesium sulfate IV (severe; bronchodilator effect)
  • IV β-agonists (rare; PICU)
  • Heliox (helium-oxygen mixture; severe)
  • NIV (BiPAP) for severe with impending failure
  • Mechanical ventilation (last resort; difficult due to high airway pressures)
304.1.0.1.7.4 Post-Discharge
  • Continue oral steroids 5-7 days
  • ICS-LABA initiation/escalation
  • Trigger review
  • Action plan
  • Spirometry follow-up
  • Allergy referral if recurrent

304.1.0.2 🩺 床邊速查

  • GINA 2024: all asthma should have ICS-formoterol (not SABA-only)
  • Step 1-5 approach; step up if uncontrolled
  • Severe asthma biologics: omalizumab (IgE) / mepolizumab/benralizumab (IL-5/IL-5R) / dupilumab (IL-4/13) / tezepelumab (TSLP, 2022)
  • Acute exacerbation: O2 + SABA + ipratropium + systemic steroids + magnesium (severe)
  • Life-threatening signs: silent chest, cyanosis, bradycardia, confusion
  • Reversibility: > 12% AND > 200 mL FEV1 improvement post-bronchodilator
  • Methacholine challenge: PC20 ≀ 8 mg/mL = positive