Abstract
The idiosyncratic activation of mast cells (MCs) in response to administration of nonselective COX inhibitors is a cardinal feature of aspirin-exacerbated respiratory disease (AERD). Older studies using MC-stabilizing drugs support a critical role for MCs and their products in driving the severe eosinophilic inflammation and respiratory dysfunction that is typical of AERD. Because patients with AERD react to all nonselective COX inhibitors regardless of their chemical structure, the mechanism of MC activation is not caused by classical, antigen-induced cross-linking of IgE receptors. Recent studies in both human subjects and animal models have revealed a complex and multifactorial process culminating in dysregulation of MC function and an aberrant dependency on COX-1-derived prostaglandin E(2) to maintain a tenuous homeostasis. This article reviews the factors most likely to contribute to MC dysregulation in patients with AERD and the potential diagnostic and therapeutic implications.