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Hindawi Publishing Corporation Journal of Allergy Volume 2012, Article ID 473863, 2 pages doi:10.1155/2012/473863 Editorial 1 2 3 2 Luis M. Teran, Stephen T. Holgate, Hae-Sim Park, and Anthony P. Sampson Department of Immunogenetics and Allergy, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK Department of Allergy and Clinical Immunology, Ajou University School of Medicine, San-5, Woncheondong, Youngtonggu, Suwon 442-721, Republic of Korea Correspondence should be addressed to Luis M. Teran, firstname.lastname@example.org Received 14 June 2012; Accepted 14 June 2012 Copyright © 2012 Luis M. Teran et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. As guest editors of this special issue of the Journal of Allergy, of the 5-lipoxygenase (5-LO) pathway that generates the we are pleased to be able to present a range of articles, both cysteinyl-leukotriene family of mediators. The most persis- reviews and original research papers, on the important topic tent anomaly described in AERD is that even in the absence of aspirin-exacerbated respiratory disease (AERD). AERD is of NSAID ingestion, the levels of cysteinyl-leukotrienes a synonym for the “aspirin triad” of asthma, nasal polyposis are constitutively elevated in the bronchoalveolar lavage and sensitivity to aspirin originally described by Widal ﬂuid, sputum, exhaled breath condensate, nasal secretions, ninety years ago. AERD patients typically experience severe saliva, blood and urine of AERD patients compared to bronchoconstriction and/or rhinoconjunctival reactions to aspirin-tolerant individuals . That the further triggering aspirin, and also to other non-steroidal anti-inﬂammatory of cysteinyl-leukotriene synthesis is important in acute drugs (NSAID), even those which they have not encountered AERD was established by studies with leukotriene synthesis previously . The reactions reﬂect non-allergic hypersensi- inhibitors and leukotriene receptor antagonists . The tivity as many AERD patients are not atopic and the reactions central mystery in AERD remains why only these patients, to NSAIDs are not usually IgE-mediated. While the aspirin and not others with comparably severe asthma, show acute triad has been described as emerging typically in early middle adverse responses to NSAIDs. This special issue of J. Allergy age, aspirin-intolerance, as determined in bronchoprovoca- includes papers from many of the leading laboratories and tion studies, may be apparent in 21% of adult asthmatics opinion leaders working on this question around the world. and 5% of asthmatic children, suggesting that it is under- In the review article by Dr Maria Garcia-Cruz and her recognised as a factor in asthma episodes . Even in the colleagues in Mexico, AERD and the cyclooxygenase theory absence of NSAID ingestion, AERD patients have relatively are discussed with special emphasis on rhinosinusitis, its severe chronic asthma with a high proportion requiring diagnosis and its treatment. Pathophysiological mechanisms long-term oral corticosteroid therapy, representing an unmet are reviewed including recent studies of cytokine and chemo- need of poorly-controlled asthma . Nasal polyposis in kine anomalies in AERD, particularly in relation to Staphylo- AERD can be severe and require recurrent surgery. coccus aureus enterotoxins which may drive abnormal allergic Many of the papers in this special issue hinge upon the responses. The theme of rhinosinusitis is extended by the key insight in the ﬁeld of AERD made by the late Professor wide-ranging review paper from the group of Prof. Meyer in Andrzej Szczeklik of Krakow. His “cyclooxygenase theory” Hamburg, writing with Dr Schafer ¨ from Erlangen, who stress recognised that the ability of NSAIDs to trigger adverse the life-threatening nature of AERD and survey its molecular reactions in AERD patients correlates with their potency mechanisms, treatment and future directions for research. as cyclooxygenase inhibitors . He extended the theory Genetic studies into AERD, including candidate gene with the realisation that arachidonic acid, the substrate of approaches and genome-wide association studies, may throw the cyclooxygenase (COX) pathway, is also the substrate light on the underlying pathological mechanisms or provide 2 Journal of Allergy genetic biomarkers for improved diagnosis and treatment. Andrzej Szczeklik was born in 1938 and graduated with a The area is expertly reviewed by Dr Palikhe and colleagues Diploma in Medicine from Krakow in 1961. His postgrad- based in Korea, while its importance is underlined by the uate training included work in Sweden at the Karolinska original research presented by Dr Falfan-Valencia and colle- Institute and at Uppsala University, and in the USA at the agues in Mexico, describing a novel association between University of North Carolina, Chapel Hill. After several years AERD and a polymorphism in the gene encoding the inﬂam- in Wroclaw, Poland, he returned to Krakow in 1972 and rose matory cytokine interleukin-1β. to become the Chairman of the Department of Medicine at Over-production of cysteinyl-leukotrienes by LTC syn- the Jagiellonian University in 1989. From 1990 to 1993, he thase and over-expression of the cysteinyl-leukotriene was president of the Copernican Academy and in 1993–1996 CysLT receptor have been postulated as central components the Vice-Rector of Jagiellonian University Medical College. of AERD pathology in the upper and lower airways . The Szczeklik was well known by his scientiﬁc reputation to paper by Dr Steinke and his colleagues in Virginia, USA, pro- all the contributors to this special issue for his lifelong vides a powerful argument that the Th2 cytokine interleukin- research into aspirin-intolerance. He led the international 4 not only upregulates LTC synthase and CysLT recep- ﬁeld following his insight in 1975 that aspirin intolerance 4 1 tors, but also down-regulates key components of the COX arises from the pharmacological activity of aspirin and other pathways, including COX-2, PGE synthase and the EP2 NSAIDs in inhibiting prostaglandin synthesis by cyclooxy- receptor, and that this accounts for the key features of AERD. genase. The “cyclooxygenase theory” is the basis of much of They further outline a molecular mechanism by which IL-4 the research focused on lipid mediators that followed in the expression could itself be modulated by aspirin. Dr Jackson ﬁeld of AERD. Szczeklik’s achievements were recognised by a and colleagues from Southampton, UK, report that the allied plethora of awards and honours, including the Gold Medal Th2 cytokine IL-13 appears not to upregulate LTC synthase of the Jagiellonian University, the AAAAI Robert A Cook in human lung macrophages, perhaps supporting this unique Lectureship, memberships of the Polish Academy of Sciences, role for IL-4 in AERD. the Royal College of Physicians in London, and the Pontiﬁcal An enduring problem in the ﬁeld of AERD is early and Academy of Sciences in the Vatican, and a number of visiting accurate diagnosis of the condition. Patients may not recog- professorships and honorary doctorates at universities in the nise an association between their use of NSAIDs and asthma UK, Europe, and Japan. During the 1980s, he was active in exacerbations, while the gold standard for many years has the Solidarity Movement and remained a major contributor been provocation testing using various oral or inhaled to the broader cultural life of his native Poland. Those who aspirin protocols that are not practicable in many clinical knew Andrzej as a friend will remember him not only as settings. The review in this issue by Dr Schafer ¨ and Prof. a gentleman and a scholar, but as an accomplished pianist Maune surveys the wide range of in vitro models that have and the author of three thoughtful and well-received books, been proposed as a basis for laboratory testing for NSAID “Catharsis: The Art of Medicine”, “Kore”, and “Immortality: sensitivity, including tests based on platelet aggregation, Promethean Dream of Medicine” published posthumously, lymphocyte transformation, and others based on levels of reﬂecting on a long life in medicine and the values that link eicosanoids and other mediators in serum or exhaled breath the humanities and sciences. He will be sadly missed by his condensate. The original paper from Dr Abuaf and col- many scientiﬁc and clinical friends across the world. leagues in Paris describes studies on a basophil activation test Luis M. Teran which shows promise in the diagnosis of AERD, at least in the Stephen T. Holgate sub-group of patients with greatest hypersensitivity. Hae-Sim Park Finally, this special issue of J. Allergy includes a paper Anthony P. Sampson by Dr Mastalerz and colleagues from the group in Krakow, Poland, led by Prof Szczeklik. Based on liquid chromatogra- phy and mass spectrometry of exhaled breath condensates, References this paper completes a broad survey of lipid anomalies in  D. D. Stevenson, “Aspirin sensitivity and desensitization for AERD, including prostanoids and novel products of the 5- asthma and sinusitis,” Current Allergy and Asthma Reports, vol. and 15-lipoxygenase pathways. This is one of the last papers 9, no. 2, pp. 155–163, 2009. to bear the name of Andrzej Szczeklik as an author before his  C.Jenkins,J.Costello, andL.Hodge,“Systematic review of pre- untimely death in February 2012, and this special issue of the valence of aspirin induced asthma and its implications for clini- Journal of Allergy is dedicated to his memory. cal practice,” BMJ, vol. 328, no. 7437, pp. 434–437, 2004.  A. Szczeklik, R. J. Gryglewski, and G. Czerniawska-Mysik, A Remembrance of Professor Andrzej Szceklik (1938–2012). “Relationship of inhibition of prostaglandin biosynthesis by This special issue of the Journal of Allergy is privileged to analgesics to asthma attacks in aspirin-sensitive patients,” BMJ, include a paper (Mastalerz et al.) coauthored by Professor vol. 1, no. 5949, pp. 67–69, 1975. Andrzej Szczeklik of Krakow University shortly before his  F. Gaber, K. Daham, A. Higashi et al., “Increased levels of cys- teinyl-leukotrienes in saliva, induced sputum, urine and blood death, aged 73, on February 3rd this year. This paper is from patients with aspirin-intolerant asthma,” Thorax, vol. 63, therefore one of Professor Szczeklik’s last publications in a no. 12, pp. 1076–1082, 2008. career in which he achieved high national and international  S. P. Farooque and T. H. Lee, “Aspirin-sensitive respiratory dis- honours and great scientiﬁc eminence for his founding ease,” Annual Review of Physiology, vol. 71, pp. 465–487, 2009. insights and enduring contributions to the ﬁeld of AERD. 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Published: Aug 14, 2012
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