An asthmatic adult with nasal polyps takes aspirin for musculoskeletal pain and within 30 minutes develops intense bronchospasm, rhinorrhoea and flushing. The biochemical event that best explains this aspirin-exacerbated respiratory disease is:
- A IgE-mediated mast cell degranulation triggered by aspirin hapten formation
- B Direct histamine release from basophils by the acidic drug
- C COX-1 inhibition diverting arachidonic acid into the 5-lipoxygenase pathway, producing exaggerated cysteinyl leukotriene release in an airway already primed for leukotriene overproduction ✓
- D Accumulation of thromboxane A2 causing bronchoconstriction
Correct answer: C. COX-1 inhibition diverting arachidonic acid into the 5-lipoxygenase pathway, producing exaggerated cysteinyl leukotriene release in an airway already primed for leukotriene overproduction
Explanation
Aspirin-exacerbated respiratory disease involves abnormal arachidonic acid metabolism: baseline overactivity of the 5-lipoxygenase pathway with elevated cysteinyl leukotrienes. Blocking COX-1 shunts substrate toward leukotriene synthesis, producing abrupt bronchospasm and upper airway symptoms within minutes to hours. The reaction is pharmacological, not IgE-mediated, ruling out option A. Thromboxane causes vasoconstriction and platelet aggregation rather than bronchoconstriction, eliminating option D.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.