Aspirin Exacerbated Respiratory Disease

As guest editors of this special issue of the Journal of Allergy, we are pleased to be able to present a range of articles, both reviews and original research papers, on the important topic of aspirin-exacerbated respiratory disease (AERD). AERD is a synonym for the " aspirin triad " of asthma, nasal polyposis and sensitivity to aspirin originally described by Widal ninety years ago. AERD patients typically experience severe bronchoconstriction and/or rhinoconjunctival reactions to aspirin, and also to other non-steroidal anti-inflammatory drugs (NSAID), even those which they have not encountered previously [1]. The reactions reflect non-allergic hypersensi-tivity as many AERD patients are not atopic and the reactions to NSAIDs are not usually IgE-mediated. While the aspirin triad has been described as emerging typically in early middle age, aspirin-intolerance, as determined in bronchoprovoca-tion studies, may be apparent in 21% of adult asthmatics and 5% of asthmatic children, suggesting that it is under-recognised as a factor in asthma episodes [2]. Even in the absence of NSAID ingestion, AERD patients have relatively severe chronic asthma with a high proportion requiring long-term oral corticosteroid therapy, representing an unmet need of poorly-controlled asthma [1]. Nasal polyposis in AERD can be severe and require recurrent surgery. Many of the papers in this special issue hinge upon the key insight in the field of AERD made by the late Professor Andrzej Szczeklik of Krakow. His " cyclooxygenase theory " recognised that the ability of NSAIDs to trigger adverse reactions in AERD patients correlates with their potency as cyclooxygenase inhibitors [3]. He extended the theory with the realisation that arachidonic acid, the substrate of the cyclooxygenase (COX) pathway, is also the substrate of the 5-lipoxygenase (5-LO) pathway that generates the cysteinyl-leukotriene family of mediators. The most persistent anomaly described in AERD is that even in the absence of NSAID ingestion, the levels of cysteinyl-leukotrienes are constitutively elevated in the bronchoalveolar lavage fluid, sputum, exhaled breath condensate, nasal secretions, saliva, blood and urine of AERD patients compared to aspirin-tolerant individuals [4]. That the further triggering of cysteinyl-leukotriene synthesis is important in acute AERD was established by studies with leukotriene synthesis inhibitors and leukotriene receptor antagonists [5]. The central mystery in AERD remains why only these patients, and not others with comparably severe asthma, show acute adverse responses to NSAIDs. This special issue of J. Allergy includes papers from many of the leading laboratories and opinion leaders working on this …