A 34-year-old woman with perennial rhinitis develops intense bronchospasm within 30 minutes of ingesting naproxen. She recalls two similar episodes after ibuprofen in the past year. Which mechanism best explains these reactions?
- A IgE-mediated mast cell degranulation against NSAID haptens
- B Excess synthesis of prostaglandin E2 from uninhibited cyclooxygenase-2
- C Shunting of arachidonic acid toward cysteinyl leukotriene production following COX-1 inhibition ✓
- D Complement-mediated activation of pulmonary macrophages
Correct answer: C. Shunting of arachidonic acid toward cysteinyl leukotriene production following COX-1 inhibition
Explanation
Aspirin-exacerbated respiratory disease results from COX-1 inhibition, which diverts arachidonic acid into the 5-lipoxygenase pathway, raising cysteinyl leukotrienes while protective prostaglandin E2 falls. The reaction is pharmacologic, not immunologic, which is why it occurs with structurally unrelated COX-1 inhibitors such as ibuprofen and naproxen. Selective COX-2 inhibitors are usually tolerated, a fact that distinguishes this from true allergic idiosyncratic reactions.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.