A patient with aspirin-exacerbated respiratory disease (Samter's triad) should avoid all NSAIDs that inhibit COX-1. The proposed mechanism for NSAID-triggered bronchospasm in these patients is:
- A COX-1 inhibition diverts arachidonic acid to the 5-lipoxygenase pathway, increasing cysteinyl leukotriene production that causes bronchoconstriction ✓
- B NSAIDs directly stimulate cysteinyl leukotriene receptors on bronchial smooth muscle
- C NSAIDs cause IgE-mediated mast cell degranulation releasing histamine and prostaglandin D2
- D COX-2 inhibition reduces anti-inflammatory prostaglandin E2 in the bronchial mucosa
Explanation
In aspirin-exacerbated respiratory disease (AERD), constitutive COX-1 activity generates prostaglandin E2 (PGE2) which tonically suppresses 5-lipoxygenase (5-LOX) activity. When COX-1 is inhibited by aspirin or NSAIDs, PGE2 falls, the 5-LOX brake is released, and arachidonic acid is shunted toward cysteinyl leukotriene (LTC4/LTD4) synthesis, causing bronchoconstriction, nasal polyp swelling, and urticaria. The reaction is pharmacological (not IgE-mediated) and occurs with all potent COX-1 inhibitors. Selective COX-2 inhibitors are generally tolerated. Treatment includes leukotriene receptor antagonists.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.