Asthma

Snapshot

• A five-year-old with severe asthma is being treated in the ER with a IV aminophylline drip. The child is slowly becoming sleepy and less responsive. Physical exam reveals less wheezing than on admission. Representative lung histology is shown.

Introduction 

• Definition
  • episodic and reversible bronchoconstriction 
    • with bronchioles being the most susceptible respiratory segment
  • result of
    • inflammation
    • bronchial smooth muscle hypertrophy and hyperactivity
• mucus plugging

Classification

• Types
  • extrinsic
    • typically seen in children with a genetic predisposition
    • type I hypersensitivty to an inhaled (external) allergen such as pollen 
      • proceeds by specific stages
        • sensitization
          • CD4 T_H2 cells produce cytokines (IL-4 and IL-5) when initially stimulated by an allergen 
            • IL-4 induces antibody isotype switch to IgE 
            • IL-5 induces eosinophil activation
        • early activation
          • mast cells are activated by cross-linking of IgE and release immune activating substances (histamine, leukotrienes, and acetylcholine) when allergen is presented again 
            • histamine results in bronchoconstriction, chemotaxis for immune cells, and mucus production
            • acetylcholine results in bronchoconstriction (parasympathetic mediated)
            • leukotrienes C₄, D₄, and E₄ induce bronchoconstriction
        • late activation
          • eosinophils are activated    
            • recruited by eotaxin
            • produce major basic protein, which causes further constriction/damage in the airways  
  • intrinsic
    • non-allergen mediated
    • induced by
      • infection
        • viral URI (RSV, rhinovirus, and parainfluenza virus)
      • behavioral
        • exertion and stress
      • chemical
        • drug sensitivity (NSAIDs and aspirin)
        • ozone produced free-radicals
  • status asthmaticus
• life-threatening asthma attack that does not respond to standard treatments

Presentation

• Symptoms
  • wheezing
  • cough
  • mucus production
  • note: a child who is becoming sleepy and less responsive is most likely failing, retaining CO₂ (case intro) and needs intubation
• Physical exam
  • tachycardia
  • tachypnea with use of accessory muscles
    • result of reduced I/E ratio

pulsus paradoxus 

• result of increased lung volume and vascular resistance
  • auscultation
    • prolonged expiratory wheezes (sometimes inspiratory)
    • high pitched sibilant rhonchi
    • dyspnea
• persistent cough with hyperinflation of the lungs

Imaging

• Chest radiograph
• normal or hyperinflation

Studies

• Labs
  • ABG
    • may initially show respiratory alkalosis
    • if CO₂ is normal, respiratory failure may be imminent 
    • elevated CO₂ (respiratory acidosis) are ominous signs and patient likely requires intubation
• Pulmonary function tests 
  • peak flows are diminished
  • obstructive pattern may be seen when symptomatic (↓ FEV1/FVC)
    • improvement with bronchodilator administration
  • high airway resistance
• Methacholine challenge   
  • provacative measure of hyperactivity in a well patient
  • functions as a muscarinic cholinergic agonist
  • reduction of FEV1 by > 20% is diagnostic of asthma
• Skin testing
  • may result in hypersensitivity response to allergen when presented into skin (really diagnoses atopy, not asthma)
• Histological changes 
  • terminal bronchioles
    • mucus plugs
      • Curschmann’s spirals  
        • presence of trapped epithelial cells killed by eosinophil produced major basic protein
      • Charcot-Leyden crystals 
        • aggregated eosinophils
    • increased mucus-producing cells
  • bronchi
    • thickened basement membrane
      • unique to asthma
    • hypertrophy of submucosal glands and smooth muscle
      • also seen in other lung disorders including chronic bronchitis
• increased immune cell presence

Treatment

• Acute exacerbation
  • oxygen
  • inhaled beta-2 agonists  
    • short acting preferred (e.g albuterol)
    • appropriate for exercise induced asthma
      • administer before exertion in known asthmatics
  • systemic corticosteroids (PO or IV)
• Status asthmaticus
  • oxygen, bronchodilators, and steroids
  • sympathomimetic bronchodilators (e.g. epinephrine)
  • intubation and mechanical ventilation
• Maintenance treatment
  • inhaled corticosteroids (mainstay)
  • long-acting bronchodilators (beta-2 agonists)
    • in combintation with inhaled corticosteroids (increased risk of death if used without inhaled corticosteroid)
  • montelukast
  • cromolyn
    • rarely used; supplemental treatment for exercise-induced asthma
  • theophylline
    • phosphodiesterase inhibitor; rarely used
  • ipratropium bromide
    • an anticholinergic that inhibits the contraction of smooth muscle
    • used in the elderly with an asthmatic component to their COPD
  • tiotropium
    • more recently shown to be efficacious and safe