A 34-year-old woman with moderate persistent asthma develops nasal polyps and then experiences severe bronchospasm within 30 minutes of taking naproxen for menstrual cramps. She has had two similar episodes after other NSAIDs. Paracetamol is tolerated without any reaction. Which mechanism best explains her NSAID reactions?
- A IgE-mediated hypersensitivity to naproxen
- B Direct histamine release from mast cells by the drug
- C Shunting of arachidonic acid toward leukotriene synthesis after COX-1 inhibition ✓
- D Complement activation via the alternative pathway
Correct answer: C. Shunting of arachidonic acid toward leukotriene synthesis after COX-1 inhibition
Explanation
Aspirin-exacerbated respiratory disease (Samter triad of asthma, nasal polyposis, and NSAID reactions) results from COX-1 inhibition by NSAIDs, which diverts arachidonic acid into the 5-lipoxygenase pathway, producing cysteinyl leukotrienes that provoke bronchospasm. Because the mechanism is pharmacologic rather than immunologic, all potent COX-1 inhibitors react, while selective COX-2 inhibitors are usually safe. The tolerance of paracetamol argues against IgE mediation, and antihistamines do not prevent these attacks.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.