A 45-year-old woman with aspirin-exacerbated respiratory disease (Samter's triad: asthma, nasal polyps, aspirin sensitivity) develops bronchospasm after taking diclofenac. What is the biochemical mechanism underlying this reaction?

• A COX-1 inhibition shunting arachidonic acid toward leukotriene synthesis, causing bronchoconstriction ✓
• B Direct histamine release from mast cells by the NSAID
• C IgE-mediated type I hypersensitivity to the NSAID
• D COX-2 inhibition reducing prostacyclin-mediated bronchodilation

Explanation

In AERD, inhibition of COX-1 by aspirin or non-selective NSAIDs diverts arachidonic acid from prostaglandin synthesis toward the 5-lipoxygenase pathway, producing excessive cysteinyl leukotrienes (LTC4, LTD4, LTE4) that cause bronchoconstriction and mucus hypersecretion. This is an idiosyncratic, non-immunologic reaction. Selective COX-2 inhibitors like celecoxib are generally tolerated in these patients because they spare COX-1.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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