Review Question - QID 108170

This vignette describes a patient who experienced acute respiratory reactions to aspirin. In addition to discontinuation of aspirin, the patient may need a leukotriene receptor antagonist, such as montelukast.

Aspirin-exacerbated respiratory disease (AERD) is associated with dysregulation of arachidonic acid metabolism, particularly with an overproduction of leukotrienes. Cyclooxygenase inhibition can further increase leukotriene accumulation due to decreased prostaglandin E2, which inhibits 5-lipooxygenase (which in turn inhibits leukotriene production). AERD can have both acute and chronic manifestations, but based on its pathophysiology, leukotriene receptor antagonists such as zafirlukast or montelukast are considered initial therapy to prevent symptoms.

Risser et al. discuss challenges in diagnosis of AERD. Notably, AERD is not a true allergic reaction since it is not mediated by IgE cross-linking. It is rare in the general population (0.07%), but has a 20% prevalence in patients with asthma. Symptomatic patients with asthma, nasal polyps, or recurrent sinusitis on aspirin should raise suspicion for AERD, but diagnosis requires a controlled aspirin challenge.

Dahlén et al. conducted a randomized trial that evaluated treatment of AERD with the 5-lipooxygenase inhibitor zileuton. Compared to placebo, the addition of zileuton to existing therapy improved both immediate and progressive pulmonary symptoms and function, whilst decreasing dependence on short-acting beta-agonists. Combination therapy of zileuton with aforementioned leukotriene receptor antagonists have not been evaluated vis-a-vis controlled trials, but are recommended by expert opinion if montelukast/zafirlukast alone does not control symptoms.

Incorrect Answers:
Answer 1: Albuterol is a short-acting beta-agonist. It is used for symptomatic relief of respiratory exacerbations, but not for prevention.
Answer 2: Tiotropium is a long-acting anticholinergic used to prevent bronchospasms in chronic obstructive pulmonary disease.
Answer 3: Prednisone is a corticosteroid used for symptomatic management in respiratory exacerbations, but not for prevention.
Answer 5: Fluticasone is an inhaled corticosteroid indicated in early management of asthma.