Abstract/Text
There is a subset of patients with bronchial asthma who are susceptible to disease exacerbation upon receiving aspirin and other nonsteroidal anti-inflammatory drugs. This is a clinical syndrome, called aspirin-induced asthma (AIA), associated with alterations in arachidonate metabolism and cysteinyl-leukotriene overproduction. The natural history and clinical characteristics of this type of asthma were studied. Sixteen clinical centres in 10 European countries provided standardized information to the specially developed patient-oriented database regarding: medical history, physical examination, diagnosis, and treatment. Diagnosis of AIA was based on a typical history, confirmed by positive aspirin provocation tests, carried out in 91% of the patients. A total of 500 patients were enrolled in the study. AIA developed according to a pattern, characterized by a sequence of symptoms. First, persistent rhinitis, appearing at a mean age of 29.7+/-12.5 yrs, then asthma, aspirin intolerance and nasal polyposis appear. The clinical presentation in different European countries was remarkably similar. In females, who outnumbered males by 2.3:1, the onset of symptoms occurred significantly earlier and the disease was more progressive and severe than in males. Atopy, present in approximately a third of patients, led to earlier manifestation of rhinitis and asthma, but not of aspirin intolerance or nasal polyposis. A family history of aspirin intolerance, recorded in 6% of patients, had a less evident effect on the course of the disease than sex or atopy. Fifty one per cent of patients, in addition to inhaled steroids, required chronic systemic corticosteroid therapy at a mean dose of 8 mg prednisone x day(-1). Surprisingly, 15% of patients were unaware of intolerance to aspirin and learnt about it only after having provocation tests performed. All over Europe, aspirin-induced asthma develops in a similar characteristic way. Its course is influenced by sex and the presence of atopy. In half of the patients, asthma is severe, and steroid-dependent. The uniform natural history of aspirin-induced asthma might suggest a common underlying principle.
Marek L Kowalski, J S Makowska, M Blanca, S Bavbek, G Bochenek, J Bousquet, P Bousquet, G Celik, P Demoly, E R Gomes, E Niżankowska-Mogilnicka, A Romano, M Sanchez-Borges, M Sanz, M J Torres, A De Weck, A Szczeklik, K Brockow
Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) - classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*.
Allergy. 2011 Jul;66(7):818-29. doi: 10.1111/j.1398-9995.2011.02557.x. Epub 2011 Feb 14.
Abstract/Text
Nonsteroidal anti-inflammatory drugs (NSAIDs) are responsible for 21-25% of reported adverse drug events which include immunological and nonimmunological hypersensitivity reactions. This study presents up-to-date information on pathomechanisms, clinical spectrum, diagnostic tools and management of hypersensitivity reactions to NSAIDs. Clinically, NSAID hypersensitivity is particularly manifested by bronchial asthma, rhinosinusitis, anaphylaxis or urticaria and variety of late cutaneous and organ-specific reactions. Diagnosis of hypersensitivity to a NSAID includes understanding of the underlying mechanism and is necessary for prevention and management. A stepwise approach to the diagnosis of hypersensitivity to NSAIDs is proposed, including clinical history, in vitro testing and/or provocation test with a culprit or alternative drug depending on the type of the reaction. The diagnostic process should result in providing the patient with written information both on forbidden and on alternative drugs.
© 2011 John Wiley & Sons A/S.
Abstract/Text
BACKGROUND: Some patients with aspirin-exacerbated respiratory disease (AERD) and eosinophilia report angina-type chest pain that occurs at rest and responds to corticosteroid therapy. The frequency of eosinophilia-associated coronary artery vasospasm in patients with AERD, a disease characterized by blood and respiratory tissue eosinophilia, however, is unknown.
OBJECTIVE: The objective of this study was to understand the cause of the chest pain described above and determine the most appropriate treatment for it.
METHODS: A chart review of 153 patients with AERD who are followed at Brigham and Women's Hospital was performed. Patients who reported any type of chest pain were assessed for the presence of cardiac risk factors, eosinophilia, and response of chest pain to a variety of treatments. Two patients with AERD and eosinophilia who had recurrent chest pain due to suspected vasospasm are described in detail, and 8 other cases are also summarized.
RESULTS: Of the 153 patients reviewed, 10 had a history of chest pain concerning for ischemia. Of the 10 patients with chest pain, 8 had undergone aspirin desensitization and initiated high-dose aspirin therapy; of these, 6 reported an increase in the frequency or severity of chest pain while on high-dose aspirin with improvement after aspirin discontinuation or dose reduction. Many patients had traditional cardiac risk factors, but none had any evidence of coronary atherosclerosis; almost all had significant eosinophilia. Their chest pain did not improve with typical antianginal treatments but did respond to corticosteroid therapy.
CONCLUSIONS: Although uncommon, patients with AERD can develop eosinophilia-associated coronary artery vasospasm, which is occasionally worsened by high-dose aspirin. Patients with AERD who present with symptoms of ischemic chest pain should be screened for eosinophilia, as early treatment with corticosteroids can be life-saving.
Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Abstract/Text
BACKGROUND: Aspirin desensitization followed by high-dose aspirin therapy is routinely performed for patients with aspirin-exacerbated respiratory disease (AERD). Little is known about the contributions of mediators other than cysteinyl leukotrienes to aspirin reactions and to the therapeutic benefit of high-dose aspirin therapy.
OBJECTIVE: We investigated differences in urinary eicosanoid metabolite levels and blood eosinophil counts in patients with AERD who tolerate and those who fail aspirin desensitization and also in patients with AERD who were successfully treated with high-dose aspirin therapy.
METHODS: Twenty-nine patients with AERD were stratified into those who tolerated aspirin desensitization (group I) and those who did not (group II). Urine was analyzed for eicosanoid metabolites at baseline, during aspirin reactions, and during high-dose aspirin therapy. Blood was analyzed for cell differentials at baseline and during aspirin therapy.
RESULTS: Basal prostaglandin D2 metabolite (PGD-M; 13.6 ± 2.7 vs 7.0 ± 0.8 pmol/mg creatinine [Cr], P < .05) and thromboxane metabolite (TX-M; 1.4 ± 0.3 vs 0.9 ± 0.1 pmol/mg Cr, P < .01) levels were higher in group II than in group I. During aspirin reactions, PGD-M levels remained unchanged, whereas TX-M levels (0.7 ± 0.1 pmol/mg Cr, P = .07) tended to decrease in group I. In contrast, PGD-M levels increased dramatically in group II (61.3 ± 19.9 pmol/mg Cr, P < .05), whereas TX-M levels did not change. The decrease in FEV1 inversely correlated with basal urinary levels of both leukotriene E4 and PGD-M. Blood eosinophil and basophil levels increased and urinary PGD-M levels (2.2 ± 0.8 pmol/mg Cr, P < .001) decreased on 2 months of high-dose aspirin therapy in group I.
CONCLUSION: Failure to tolerate aspirin desensitization in a subset of patients with AERD is associated with prostaglandin D2 overproduction. The increase in blood eosinophil and basophil counts during high-dose aspirin therapy might reflect the functional consequences of decreased prostaglandin D2 release and the therapeutic benefit of aspirin.
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Chihiro Mitsui, Keiichi Kajiwara, Hiroaki Hayashi, Jun Ito, Haruhisa Mita, Emiko Ono, Noritaka Higashi, Yuma Fukutomi, Kiyoshi Sekiya, Takahiro Tsuburai, Kazuo Akiyama, Kazuhiko Yamamoto, Masami Taniguchi
Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease.
J Allergy Clin Immunol. 2016 Feb;137(2):400-11. doi: 10.1016/j.jaci.2015.05.041. Epub 2015 Jul 17.
Abstract/Text
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by respiratory reactions on ingestion of COX-1 inhibitors and cysteinyl leukotriene overproduction. The hypersensitivity reaction is induced by low doses of aspirin that inhibit COX-1 in platelets.
OBJECTIVE: We sought to explore the role of platelets in the pathogenesis of AERD in patients under stable conditions and during an aspirin challenge test.
METHODS: Stable patients with AERD (n = 30), aspirin-tolerant asthma (ATA; n = 21), or idiopathic chronic eosinophilic pneumonia (n = 10) were enrolled. Platelet activation was estimated based on expression levels of P-selectin (CD62P), CD63, CD69, and GPIIb/IIIa (PAC-1) in peripheral platelets; percentages of circulating platelet-adherent leukocytes; and plasma levels of soluble P-selectin (sP-selectin) and soluble CD40 ligand (sCD40L).
RESULTS: In the stable condition, expression of all surface markers on platelets, the percentage of platelet-adherent eosinophils, and the plasma levels of sP-selectin and sCD40L were significantly higher in patients with AERD compared with those in patients with ATA. P-selectin and CD63 expression on platelets and plasma sP-selectin and sCD40L levels were positively correlated with the percentage of platelet-adherent eosinophils. Among these markers, P-selectin expression and plasma sP-selectin levels positively correlated with urinary concentrations of leukotriene E4. Additionally, plasma sP-selectin and sCD40L levels were negatively correlated with lung function. In contrast, platelet activation markers in patients with AERD did not change during the aspirin challenge test.
CONCLUSION: Peripheral platelets were activated more in patients with stable AERD compared with those in patients with stable ATA, patients with idiopathic chronic eosinophilic pneumonia, and control subjects. Platelet activation was involved in cysteinyl leukotriene overproduction and persistent airflow limitations in patients with AERD.
Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Hiroaki Hayashi, Chihiro Mitsui, Eiji Nakatani, Yuma Fukutomi, Keiichi Kajiwara, Kentaro Watai, Kiyoshi Sekiya, Takahiro Tsuburai, Kazuo Akiyama, Yoshinori Hasegawa, Masami Taniguchi
Omalizumab reduces cysteinyl leukotriene and 9α,11β-prostaglandin F2 overproduction in aspirin-exacerbated respiratory disease.
J Allergy Clin Immunol. 2016 May;137(5):1585-1587.e4. doi: 10.1016/j.jaci.2015.09.034. Epub 2015 Nov 11.
Abstract/Text
