Asthma Study Guide

📖 Core Concepts Asthma – chronic inflammatory disease of the bronchioles causing variable, reversible airflow obstruction and bronchospasm. Inflammatory cells – eosinophils, T‑lymphocytes, macrophages, neutrophils; release cytokines, histamine, leukotrienes. Airway hyper‑responsiveness (AHR) – inflamed airways over‑react to triggers → reversible narrowing. Type 2‑high vs. Type 2‑low Type 2‑high: IL‑4, IL‑5, IL‑13 driven, eosinophilia, responds to anti‑IL‑5/IL‑4R/IgE biologics. Type 2‑low: lacks these cytokines, often neutrophilic, requires non‑type‑2 strategies. Phenotype vs. Endotype – phenotype = clinical presentation (e.g., atopic, exercise‑induced); endotype = underlying molecular pathway. Severity classification (exacerbation) – based on peak expiratory flow (PEF): Mild ≥ 200 L/min (≥ 50 % predicted) Moderate 80–200 L/min (25–50 % predicted) Severe ≤ 80 L/min (≤ 25 % predicted) --- 📌 Must Remember Epidemiology: 262 million affected worldwide (2019); 461 000 deaths. Diagnostic spirometry criterion: ≥ 12 % and ≥ 200 mL increase in FEV₁ after bronchodilator. PEF variability: ≥ 20 % variation on ≥ 3 days/week for 2 weeks supports diagnosis. Key triggers: allergens (dust mites, animal dander, mould), cold‑dry air, exercise, pollutants, NSAIDs/aspirin, β‑blockers. First‑line rescue: Short‑acting β₂‑agonist (SABA) ± anticholinergic (ipratropium). Controller hierarchy: Inhaled corticosteroid (ICS) → add LABA → add leukotriene antagonist → consider biologics (anti‑IgE, anti‑IL‑5, anti‑IL‑4R). Acute exacerbation meds: SABA (MDI + spacer or nebulizer) → systemic corticosteroid → IV magnesium sulfate (moderate‑severe). Biologic eligibility: Severe, uncontrolled Type 2‑high asthma with eosinophilia or high IgE. --- 🔄 Key Processes Pathogenesis Allergen/irritant → airway epithelium releases cytokines → recruitment of eosinophils/T‑cells → mucus hypersecretion & smooth‑muscle hypertrophy → AHR. Acute Exacerbation Management Assess severity (PEF, accessory muscle use, oxygen saturation). Give humidified O₂ if SpO₂ < 92 %. Administer SABA via MDI + spacer (or nebulizer if unable). Add ipratropium for moderate/severe attacks. Oral/IV corticosteroid (prednisone ≈ 1 mg/kg or dexamethasone). IV magnesium sulfate (≤ 3 g over 20 min) for refractory cases. Consider non‑invasive ventilation, then mechanical ventilation as last resort. Stepwise Pharmacologic Therapy (GINA/NHLBI) Step 1: PRN SABA only. Step 2: Low‑dose ICS. Step 3: Low‑dose ICS + LABA or low‑dose ICS + LTRA. Step 4: Medium‑dose ICS + LABA. Step 5: High‑dose ICS + LABA ± LTRA ± biologic. --- 🔍 Key Comparisons Type 2‑high vs. Type 2‑low High: eosinophilia, ↑ FeNO, responds to anti‑IL‑5/IL‑4R/IgE. Low: neutrophilic/ paucigranulocytic, limited response to type‑2 biologics. Atopic (extrinsic) vs. Non‑atopic (intrinsic) asthma Atopic: allergen‑driven, family history of allergy, high IgE. Non‑atopic: no allergen sensitization, often adult‑onset. Asthma vs. COPD Asthma: reversible obstruction, eosinophilic inflammation, early‑life triggers. COPD: largely irreversible, neutrophilic inflammation, smoking history. SABA via spacer vs. nebulizer Spacer: better lung deposition, less drug waste, preferred in children. Nebulizer: useful when patient cannot coordinate inhaler use. LABA alone vs. LABA + ICS LABA alone → ↑ risk of severe asthma events. Combined → synergistic control, lower risk. --- ⚠️ Common Misunderstandings “Normal FeNO rules out asthma.” – FeNO reflects eosinophilic (type 2) inflammation only; type 2‑low asthma can have normal FeNO. “If PEF improves >200 L/min, asthma is confirmed.” – Must also meet ≥ 12 % increase; a single reading isn’t sufficient. “Inhaled steroids have no systemic effects.” – High‑dose or long‑term use can cause adrenal suppression, bone loss, growth delay in children. “All asthma is atopic.” – Up to 30 % are non‑atopic, especially adult‑onset. “Oral steroids are safe for mild attacks.” – Systemic steroids are reserved for moderate‑severe exacerbations due to side‑effects. --- 🧠 Mental Models / Intuition “Balloon‑and‑rubber‑band” model – Inflammation inflates the balloon (airway wall thickening) while the rubber band (smooth‑muscle) tightens → explains reversible obstruction and hyper‑responsiveness. “Trigger‑Response‑Control” loop – Identify trigger → observe symptom response → apply appropriate control (quick‑relief vs. controller). Visualize each step as a switch that can be turned on (exacerbation) or off (controlled). --- 🚩 Exceptions & Edge Cases Asthma‑COPD Overlap Syndrome (ACOS) – Mixed reversible/irreversible obstruction; higher morbidity; may need combined bronchodilator + anti‑inflammatory strategy. Aspirin‑Exacerbated Respiratory Disease (AERD) – Triad of asthma, nasal polyps, aspirin/NSAID sensitivity; consider leukotriene modifiers and avoidance of COX‑1 inhibitors. Exercise‑induced bronchoconstriction – Occurs with dry, cold air; pre‑exercise SABA (≤ 15 min before) is effective. Children <5 y – Leukotriene receptor antagonists are preferred add‑on after low‑dose ICS; LABA benefit uncertain. Non‑selective β‑blockers – Can precipitate bronchospasm; cardio‑selective agents are safer but still used with caution. --- 📍 When to Use Which Spirometry – Initial diagnosis, stepwise monitoring, assess reversibility. Peak Flow Monitoring – Home monitoring for variable disease, especially in children or occupational asthma. Methacholine Challenge – When spirometry is normal but suspicion remains; not disease‑specific. ICS – All patients with persistent symptoms; first‑line controller. Add‑on LABA – When low‑dose (or medium‑dose) ICS alone fails to achieve control. Leukotriene Antagonist – Children <5 y, aspirin‑sensitive patients, or as steroid‑sparing option. Biologics (anti‑IgE, anti‑IL‑5, anti‑IL‑4R) – Severe, uncontrolled Type 2‑high asthma with high eosinophils/IgE despite maximal inhaled therapy. IV Magnesium Sulfate – Moderate‑severe acute attack refractory to SABA + systemic steroids. Spacer vs. Nebulizer – Spacer for most patients; nebulizer when coordination impossible or severe distress. --- 👀 Patterns to Recognize Nocturnal/worsening early‑morning symptoms → suggests uncontrolled asthma. ≥ 20 % PEF variability over 2 weeks → diagnostic clue. Eosinophilia + high FeNO → Type 2‑high endotype → candidate for biologics. Rapid response to systemic steroids in an acute attack → confirms inflammatory component. Exacerbation triggered by NSAIDs or alcohol → think AERD. --- 🗂️ Exam Traps “Peak flow < 200 L/min = severe asthma” – severity also depends on % predicted; absolute values vary with age/size. Choosing LABA as monotherapy – many questions list LABA alone as a distractor; always combine with ICS. Assuming all patients need a bronchodilator before spirometry – bronchodilator is used after baseline spirometry to assess reversibility. Misreading the 12 %/200 mL bronchodilator response as “either/or” – both criteria must be met. Confusing ACOS with pure asthma – look for fixed airflow limitation and smoking history. Believing that oral steroids are first‑line for any exacerbation – only indicated for moderate‑severe attacks; mild attacks often managed with SABA alone. ---