What is the underlying pathophysiological mechanism in aspirin exacerbated respiratory disease?

Aspirin exacerbated respiratory disease (AERD) is a clinical condition characterized by asthma, nasal polyps, and sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). The underlying pathophysiological mechanism involves the inhibition of cyclooxygenase (COX) enzymes by aspirin, which leads to decreased synthesis of prostaglandins. Consequently, this inhibition creates a metabolic shift that favors the lipoxygenase pathway.

As a result, there is an increased production of leukotrienes, particularly leukotriene B4 and cysteinyl leukotrienes, which are potent pro-inflammatory mediators. These leukotrienes are responsible for bronchoconstriction, increased airway hyperreactivity, and overall exacerbation of respiratory symptoms in patients with AERD.

This pathway underscores why the correct answer is related to the activation of lipoxygenase leading to leukotriene production. This mechanism is central to the exacerbation of the respiratory symptoms experienced by individuals with aspirin sensitivity, demonstrating the complex interplay between arachidonic acid metabolism and respiratory health in this condition.

The other options do not accurately reflect the critical events in aspirin exacerbated respiratory disease. Histamine release from mast cells is more associated with immediate allergic responses rather