Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyposis, and pathognomonic respiratory reactions to aspirin (Samter’s triad). It has been estimated that this syndrome affects 7% of adults with asthma and 14% of those who have severe asthma. Pathologically, AERD is characterized by marked eosinophilic inflammation and ongoing mast-cell activation in the respiratory mucosa. The frequent recurrence of nasal polyps after surgery, as well as the requirement for high-dose glucocorticoids to manage the asthma, reflect the aggressive, persistent nature of the disease. The typical onset is in adulthood, with or without preexisting asthma, rhinitis, or atopy. An absence of familial clustering argues against a strong genetic basis, and the identification of variants of candidate genes in small studies has not been replicated.
All nonsteroidal antiinflammatory drugs (NSAIDs) that inhibit both cyclooxygenase (COX)-1 and COX-2 may provoke the pathognomonic reactions in AERD; these reactions are accompanied by idiosyncratic activation of respiratory tract mast cells. In contrast, patients with AERD can usually be treated with COX-2–selective drugs without having these reactions. The fact that structurally diverse NSAIDs that block COX-1 all provoke reactions reflects an enigmatic requirement for COX-1–derived prostaglandins to maintain a tenuous homeostasis. Curiously, the reactions also induce a refractory state in which NSAIDs can be used with diminished or no sequelae (desensitization); in fact, after desensitization, high-dose aspirin has therapeutic benefits. Insights into the mechanisms responsible for the pathogenesis of AERD or its treatment have been limited.
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