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Updated: Mar 28 2022


  • 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 TH2 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 pulsus paradoxus
        • result of reduced I/E ratio
        • 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
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