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Targeted eicosanoid lipidomics of exhaled breath condensate provide a distinct pattern in the aspirin-intolerant asthma phenotype - 11/08/11

Doi : 10.1016/j.jaci.2010.12.1108 
Marek Sanak, MD, Anna Gielicz, MSc, Grażyna Bochenek, MD, Marek Kaszuba, MD, Ewa Niżankowska-Mogilnicka, MD, Andrew Szczeklik, MD
Department of Medicine, Jagiellonian University Medical College, Krakow, Poland 

Reprint requests: Andrew Szczeklik, MD, Department of Medicine, Jagiellonian University Medical College, Ul. Skawinska 8, 31-066 Krakow, Poland.

Abstract

Background

Eicosanoids, important signaling and inflammatory molecules, are present in exhaled breath condensate (EBC) in very low concentrations, requiring highly sensitive analytic methods for their quantification.

Objective

We sought to assess a vast platform of eicosanoids in different asthma phenotypes, including aspirin-intolerant asthma, by means of a recently developed analytic approach based on mass spectrometry.

Methods

EBC from 115 adult asthmatic subjects (62 with aspirin intolerance) and 38 healthy control subjects were assessed quantitatively for 19 eicosanoids by using complementary HPLC, gas chromatography–mass spectrometry, or both. Palmitic acid concentrations were used as a marker for dilution of condensate samples.

Results

Asthma was characterized by an increase in arachidonate lipoxygenase products and cysteinyl leukotrienes. The COX pathway was also significantly upregulated in asthmatic subjects. Subjects with aspirin-intolerant asthma were distinguished by a sharp increase in the level of prostaglandin D2 and E2 metabolites; their 5- and 15-hydroxyeicosateraenoic acid levels were also higher than in aspirin-tolerant subjects. A classical discriminant analysis permitted us to classify correctly 99% of asthmatic subjects within the study population; the specificity of the analysis was 97%. The eicosanoid profiling allowed for 92% correct classification of aspirin-intolerant subjects.

Conclusions

The highly sensitive eicosanoid profiling in EBC makes it possible to detect alterations in asthma, especially in its distinct phenotype characterized by hypersensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. This permits us to discriminate asthmatic subjects from healthy subjects, as well as to distinguish the 2 asthma phenotypes based on the presence or absence of aspirin hypersensitivity.

El texto completo de este artículo está disponible en PDF.

Key words : Exhaled breath condensate, asthma, aspirin intolerance, eicosanoids, mass spectrometry

Abbreviations used : AIA, ATA, EBC, 8-iso-PGF2⍺, 11-dehydro-TXB2, GC-MS, HPLC-MS/MS, HETE, LO, LT, 9⍺,11β-PGF2, PG, PGEM, 6-keto-PGF1⍺


Esquema


 Supported by a grant from Iceland, Liechtenstein, and Norway through the European Economic Area (EEA) Financial Mechanism and by the U-BIOPRED project carried out under the Innovative Medicines Initiative.
 Disclosure of potential conflict of interest: M. Sanak, A. Gielicz, G. Bochenek, M. Kaszuba, E. Nizankowska-Mogilnicka, and A. Szczeklik have received research support from the European Community and the Polish Ministry of Science and Higher Education.


© 2011  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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P. 1141 - mai 2011 Regresar al número
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