Harvey's Garden

Asthma

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tags—
aliases

6 min read

Etiology

  • Risk factors for asthma include:
    • Family history of asthma
    • Past history of allergies
    • Atopic dermatitis
    • Low socioeconomic status
  • Allergic asthma (extrinsic asthma) vs Nonallergic asthma (intrinsic asthma)
    • Allergic asthma (extrinsic asthma)
      • Cardinal risk factor: atopy
      • Environmental allergens: pollen (seasonal), dust mites, domestic animals, mold spores
      • Allergic occupational asthma from exposure to allergens in the workplace (e.g., flour dust)
    • Nonallergic asthma (intrinsic asthma)
      • Viral respiratory tract infections (one of the most common stimuli, especially in children)
      • Cold air
      • Physical exertion (laughter, exercise-induced asthma)
      • Gastroesophageal reflux disease (GERD): often exists concurrently with asthma
      • Chronic sinusitis or rhinitis
      • Medication: aspirin/NSAIDS (aspirin-induced asthma), beta blockers
      • Stress
      • Irritant-induced occupational asthma (e.g., from exposure to solvents, ozone, tobacco or wood smoke, cleaning agents)

Tip

  • Allergic asthma (extrinsic asthma): A type of asthma triggered by allergens (e.g., pollen, dust mites, mold spores, pet allergens). Typically onset in childhood.
  • Nonallergic asthma (intrinsic asthma): A type of asthma that typically develops in patients > 40 years of age.

Pathophysiology

Common underlying pathophysiology

  • Core Pathophysiology
    • Chronic disorder of airway hyperresponsiveness, inflammation, and reversible bronchoconstriction.
      • Symptoms are primarily caused by inflammation of the terminal bronchioles, which are lined with smooth muscle but lack the cartilage found in larger airways.
    • Key Cells: Eosinophils, Mast Cells, Th2 lymphocytes.
    • Airflow: ↓ FEV1/FVC ratio, reversible with bronchodilators.
  • Allergic (Extrinsic) Asthma
    • Type I Hypersensitivity Reaction (most common type).
    • Mechanism: Allergen exposure → APC presents to Th2 cell → Th2 secretes:
      • IL-4/IL-13: Stimulates B-cells to produce IgE.
      • IL-5: Recruits and activates eosinophils.
    • Action: IgE coats mast cells. Re-exposure → mast cell degranulation → release of histamine & leukotrienes → bronchospasm.
    • Late Phase: Eosinophil-mediated inflammation damages epithelium.
  • Non-Allergic (Intrinsic) Asthma
    • Triggers: Viral infections (RSV, rhinovirus), cold air, stress.
    • Mechanism: Not IgE-mediated. Normal serum IgE. Inflammation is driven by non-atopic stimuli.
      • Iirritant enters lung → ↑ release of neutrophils → submucosal edema → airway obstruction
  • Aspirin-Exacerbated Respiratory Disease (AERD)
    • Samter’s Triad: Asthma + Nasal Polyps + Aspirin/NSAID sensitivity.
    • Mechanism: NSAID inhibition of COX pathway shunts arachidonic acid to the lipoxygenase pathway → ↑ Leukotrienes → severe bronchoconstriction.
  • Classic Pathology Findings
    • Curschmann spirals: Whorled mucus plugs.
    • Charcot-Leyden crystals: Crystalline breakdown products of eosinophils.
    • Airway Remodeling (Chronic): Smooth muscle hypertrophy and sub-basement membrane fibrosis.

Clinical features

Subtypes and variants

  • Allergic asthma
    • Most common phenotype
    • Begins with intermittent symptoms in childhood
    • Triggered by allergens
    • Usually associated with atopy (e.g., eczema, rhinitis)
    • Responds well to ICS-containing treatment
  • Nonallergic asthma
    • Less common than allergic asthma
    • Triggered by, e.g., viral upper respiratory tract infections, cold air, GERD
    • Not associated with atopy
    • Responds poorly to ICS-containing treatment
  • Cough variant asthma: a type of asthma characterized by chronic dry cough without other typical symptoms of asthma
    • Cough often worsens at night.
  • Aspirin-exacerbated respiratory disease
  • Occupational asthma
    • Diagnosis
      • Initial/Screening: Serial Peak Expiratory Flow (PEF) monitoring (logging values at work vs. days off) for 2–4 weeks.
      • Key Labs/Imaging: Baseline spirometry demonstrating reversible airflow obstruction (FEV1/FVC < 0.70; ↑ FEV1 by >12% and >200 mL post-bronchodilator).
      • Confirmatory/Gold Standard: Specific Inhalation Challenge (SIC) with the suspected workplace agent (often reserved for specialized centers).
      • Alternative Testing: Methacholine challenge test (high negative predictive value to rule out asthma if spirometry is normal). Skin prick/serum specific IgE testing for HMW agents.Ï

Differential diagnostics

FeatureCardiogenic “Asthma” (Heart Failure)Bronchial Asthma
PathophysiologyLV failure → pulmonary edema → airway narrowing.Airway inflammation (IgE/eosinophilic) → bronchoconstriction.
Patient ProfileOlder patient, history of CHF, HTN, MI.Younger patient, history of atopy (eczema, allergies).
Key SymptomsOrthopnea, PND, pink frothy sputum.Nocturnal cough, triggered by allergens/exercise.
Physical ExamJVD, S3 gallop, bibasilar crackles/rales.Diffuse expiratory wheezing, often normal between exacerbations.
Key Diagnostics↑ BNP, Kerley B lines & cardiomegaly on CXR.PFTs show reversible obstruction post-bronchodilator.
ManagementDiuretics (e.g., Furosemide), Nitrates, O2, BiPAP.Bronchodilators (e.g., Albuterol), Corticosteroids.

Diagnostics

Spirometry

  • Supportive findings: Expiratory airway limitation: i.e., ↓ FEV1 and ↓ FEV1/FVC ratio
  • Bronchodilator Responsiveness Testing:
    • Used when the patient has abnormal baseline spirometry showing obstruction (FEV1/FVC ≤70%)
    • Tests if the obstruction is reversible (suggesting asthma) or fixed (suggesting conditions like COPD)
    • Not useful if current spirometry is normal, even if the patient has asthma symptoms
    • Quick test: perform spirometry → give bronchodilator → repeat spirometry
  • Bronchial Challenge Testing:
    • Identify airway hyperresponsiveness and bronchoconstriction in response to direct, nonallergic stimuli (e.g., methacholine, histamine) or indirect stimuli (e.g., exercise, hyperventilation).
    • Used when patient has symptoms suggestive of asthma but normal baseline spirometry
    • Tests for airway hyperresponsiveness by attempting to provoke bronchospasm
    • Particularly useful for patients with intermittent symptoms who are asymptomatic during office visits
    • More time-intensive: involves giving increasing doses of the provocative agent and measuring response

Allergen Testing

  • Sensitization vs. Allergy: A (+) Skin Prick Testing (SPT) or Serum Specific IgE (sIgE) only indicates sensitization. Diagnosis of allergy requires (+) test AND clinical symptoms on exposure. c

Treatment

Approach

1. Chronic Asthma Management (Stepwise)

  • Prerequisite: Assess adherence and inhaler technique before stepping up therapy.
  • Step 1 (Intermittent): Symptoms < 2 days/week, nighttime awakenings 2x/month.
    • Preferred (GINA Track 1): As-needed low-dose ICS-formoterol.
    • Alternative (Track 2): As-needed SABA + low-dose ICS whenever SABA is taken.
  • Step 2 (Mild Persistent): Symptoms > 2 days/week (but not daily), nighttime awakenings 3-4x/month.
    • Preferred: Daily low-dose ICS + as-needed SABA, OR as-needed low-dose ICS-formoterol.
    • Alternative: LTRA (montelukast).
  • Step 3 (Moderate Persistent): Symptoms daily, nighttime awakenings > 1x/week (not nightly).
    • Preferred: Daily low-dose ICS-LABA + as-needed SABA, OR low-dose ICS-formoterol as SMART (Single Maintenance and Reliever Therapy).
  • Step 4 (Severe Persistent): Symptoms throughout the day, nighttime awakenings nightly.
    • Preferred: Daily medium-dose ICS-LABA as SMART or maintenance + SABA reliever.
    • Alternatives: Add LAMA (tiotropium) or LTRA.
  • Step 5: High-dose ICS-LABA + phenotypic assessment for biologic therapies (e.g., omalizumab [anti-IgE], mepolizumab [anti-IL-5]).
  • Refractory: Low-dose oral corticosteroids (OCS) (minimize use due to systemic adverse effects).

2. Acute Asthma Exacerbation

  1. Oxygen: Maintain 93-95% (92-95% in pregnancy).
  2. Bronchodilators: Inhaled SABA (albuterol) + SAMA (ipratropium) nebulizers every 20 mins or continuously for the first hour.
  3. Systemic Corticosteroids: IV methylprednisolone or PO prednisone (give early; takes 4-6 hours to work).
  4. Refractory (Severe): IV (single dose, induces smooth muscle relaxation).
  5. Intubation & Mechanical Ventilation:
    • Critical Exam Indicator: Normalization of on ABG (or rising ) in a tachypneic patient. Indicates respiratory muscle fatigue and impending respiratory failure. c
    • Other indications: Silent chest on auscultation (no air movement), altered mental status.

Antileukotrienes

Leukotriene receptor antagonists (LTRAs)

  • Montelukast, Zafirlukast
  • Uses
    • Exercise-induced
    • Prevent leukotrienes from binding to their receptors (CysLT1)→ ↓ bronchoconstriction and inflammation
    • Asthma aspirin-induced asthma
    • Long-term maintenance treatment (particularly in children)

Leukotriene pathway modifiers

  • Zileuton
  • Inhibit 5-lipoxygenase → ↓ production of leukotrienes → ↓ bronchoconstriction and inflammation
  • Uses
    • Exercise-induced asthma
    • Aspirin-induced asthma

Mnemonic

Antileukotrienes -> Montelukast, zafirlukast, zileuton

Long-acting muscarinic antagonists (LAMA)

  • Tiotropium bromide（噻托溴铵）
  • Long-term maintenance treatment

Mast cell stabilizers (chromones)

  • Cromolyn
  • Inhibit mast cell degranulation and prevent release of preformed chemical mediators.
  • Uses
    • Preventive treatment prior to exercise

Biologics

Anti-IgE antibodies

  • Omalizumab 单抗记忆
  • Binds to serum IgE → ↓ expression of high-affinity IgE receptors (FcεRI) on mast cells and basophils
  • Uses
    • Select cases of severe asthma

IL-5 antibodies

  • mepolizumab, reslizumab,benralizumab
  • Block the effects of IL-5 on eosinophils → ↓ chemotaxis and ↓ cell differentiation, maturation, and activation
  • Uses
    • Refractory severe eosinophilic asthma

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