304.3 🏥 內科專科考前版

304.3.1 Mechanistic Deep Dive

304.3.1.1 Type 2 Inflammation Cascade

  • Allergen → epithelial cells release TSLP, IL-25, IL-33 (alarmins)
  • Activate ILC2s → produce IL-4, IL-5, IL-13
  • Th2 cells from naive Th0
  • IL-4 → IgE class switching
  • IL-5 → eosinophil maturation + activation
  • IL-13 → mucus hypersecretion + airway remodeling

304.3.1.2 Airway Remodeling

  • Smooth muscle hyperplasia
  • Goblet cell hyperplasia
  • Subepithelial fibrosis
  • Angiogenesis
  • May be partially irreversible

304.3.1.3 Bronchial Hyperreactivity

  • Hyperresponsiveness to triggers
  • Methacholine challenge tests
  • Reduced as asthma controlled

304.3.2 Recent Trials & Updates

304.3.2.2 SOURCE (2022) — Tezepelumab + OCS Sparing

  • Reduced OCS dependence
  • Confirmed in severe asthma

304.3.2.3 QUEST (2018) — Dupilumab

  • Severe asthma
  • Reduced exacerbations + improved FEV1
  • Approved for asthma + atopic dermatitis + CRSwNP

304.3.2.4 STRATOS-1/2 (2019) — Tralokinumab

  • Anti-IL-13
  • For severe atopic dermatitis (more)
  • Asthma response heterogeneous

304.3.2.5 Single MART (Maintenance + Reliever) — Multiple Trials

  • ICS-formoterol single inhaler
  • Improved control + reduced exacerbations
  • GINA 2024 emphasized

304.3.2.6 Allergen Immunotherapy

  • Subcutaneous (SCIT) or sublingual (SLIT)
  • Effective for allergic asthma
  • Long-term benefit
  • Risk of anaphylaxis

304.3.2.7 Bronchial Thermoplasty

  • Radiofrequency to airway smooth muscle
  • For severe asthma with bronchospasm
  • Modest efficacy
  • Class IIb in most guidelines

304.3.2.8 Asthma + Microbiome

  • Gut + airway microbiome
  • Early life exposures affect risk
  • Prevention research

304.3.3 High-Yield Specialist Points

304.3.3.1 Eosinophilic vs Allergic Asthma

  • Allergic (T2-high): ↑ IgE + ↑ eosinophils + ↑ FeNO; childhood onset
  • Eosinophilic non-allergic (T2-high): ↑ eosinophils + ↑ FeNO without IgE; adult onset
  • Treatment overlap (biologics)
  • Eos > 300 + FeNO > 25 = predictive of dupilumab response

304.3.3.2 T2-Low Asthma

  • Neutrophilic
  • Often severe + steroid resistant
  • Tezepelumab effective (upstream alarmin blockade)
  • Azithromycin chronic effects (AMAZES trial)

304.3.3.3 AERD (Samter’s Triad)

  • Asthma + chronic rhinosinusitis with nasal polyps + aspirin/NSAID sensitivity
  • COX-1 inhibition → leukotriene shift
  • Aspirin desensitization (challenges + continuation) can be done
  • Dupilumab very effective
  • Avoid all NSAIDs unless desensitized

304.3.3.4 Pregnancy + Asthma

  • Uncontrolled asthma worse than medications for fetus
  • ICS-formoterol safe (budesonide best evidence)
  • Avoid high-dose OCS if possible
  • Continue biologics (limited data; case-by-case)

304.3.3.5 Occupational Asthma

  • Sensitizer-induced (allergic): latency period; isocyanates, flour, animal proteins
  • Irritant-induced (RADS - Reactive Airways Dysfunction Syndrome): no latency; high-dose exposure (chlorine, ammonia)
  • Diagnosis: occupational history + serial PEF + specific bronchial challenge
  • Treatment: cessation of exposure + ICS-LABA + workers’ compensation

304.3.3.6 Severe Asthma Phenotyping

  • Step 1: assess adherence + technique + diagnosis
  • Step 2: identify phenotype (T2-high vs T2-low)
  • Step 3: select biologic
  • Step 4: monitor response
  • Step 5: switch if no response

304.3.3.7 Exercise-Induced Bronchoconstriction (EIB)

  • Up to 90% of asthmatics
  • Cold/dry air, vigorous exercise
  • Pre-exercise SABA (15-30 min before)
  • ICS daily reduces baseline + EIB
  • LTRA option
  • Mannitol challenge for diagnosis

304.3.3.8 Cough-Variant Asthma

  • Cough as sole symptom
  • Normal baseline spirometry
  • Positive methacholine challenge
  • ICS-formoterol responsive
  • Common cause of chronic cough

304.3.3.9 Aspirin Desensitization in AERD

  • Performed in supervised setting
  • Stepwise dose escalation
  • Continued daily aspirin (650 mg)
  • Reduced polyp + sinus issues
  • Improved asthma control

304.3.4 Pearls

  • GINA 2024: ICS-formoterol for all asthma reliever
  • Biologics revolution: omalizumab (IgE), anti-IL-5 family, dupilumab (IL-4/13), tezepelumab (TSLP — T2-high + T2-low)
  • AERD: Samter’s triad; aspirin desensitization option; dupilumab very effective
  • Acute exacerbation: O2 + SABA + ipratropium + steroids + magnesium
  • MART (maintenance + reliever): single inhaler ICS-formoterol; reduces exacerbations
  • Tezepelumab (NAVIGATOR 2021): first effective in T2-low severe asthma
  • EIB: pre-exercise SABA; ICS daily reduces baseline