A patient with aspirin-exacerbated respiratory disease (AERD/Samter's triad) develops bronchospasm after aspirin ingestion. The mechanism is:
- A IgE-mediated mast cell degranulation releasing histamine in the bronchi
- B COX-1 inhibition diverts arachidonic acid from prostaglandin synthesis towards 5-lipoxygenase pathway, causing excess cysteinyl leukotriene production ✓
- C Aspirin inhibits COX-2, reducing bronchodilatory PGI2 production
- D Aspirin activates TRP ion channels in bronchial epithelium causing reflex bronchoconstriction
Correct answer: B. COX-1 inhibition diverts arachidonic acid from prostaglandin synthesis towards 5-lipoxygenase pathway, causing excess cysteinyl leukotriene production
Explanation
In AERD patients, mast cells constitutively overexpress 5-lipoxygenase. When aspirin inhibits COX-1, the arachidonic acid that would have been converted to PGE2 (which normally inhibits 5-LO via EP2 receptors) is shunted into the 5-LO pathway. The resulting surge in cysteinyl leukotrienes (LTC4, LTD4, LTE4) causes bronchospasm, nasal polyps, and urticaria. This is a pharmacological (pseudo-allergic) reaction, not IgE-mediated, and all NSAIDs that inhibit COX-1 can trigger it. Leukotriene receptor antagonists (montelukast) help manage AERD.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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