Eoxins: A new inflammatory pathway in childhood asthma - 07/08/11
, Marek Sanak, MD b, Astri Maria Lang, MD a, Anna Gielicz, MSc b, Petter Mowinckel, MSc a, Karin Cecilie Lødrup Carlsen, MD a, c, Kai-Håkon Carlsen, MD a, c, Andrzej Szczeklik, MD b
Reprint requests: Christine Sachs-Olsen, MD, Department of Paediatrics, Oslo University Hospital, Sognsvannsveien 20, NO-0027 Oslo, Norway.Abstract |
Background |
Increased levels of leukotrienes (LTs) in exhaled breath condensate (EBC) are associated with asthma and bronchial hyperresponsiveness (BHR), whereas eicosanoids generated through the 15-lipoxygenase (LO) pathway (15-hydroxyeicosatetraenoic acid [HETE] and eoxins) have been less studied.
Objective |
We investigated whether metabolites of the 5- and 15-LO pathways in EBC are associated with childhood asthma, asthma severity, and clinical parameters.
Methods |
The present study included 131 school-aged children (27 children with problematic severe asthma, 80 children with mild-to-moderate asthma, and 24 healthy children) from the Severe Asthma Recognized in Childhood study and 19 children with other nonasthmatic chronic lung diseases. Clinical work-up included spirometry, fractional exhaled nitric oxide measurements, skin prick testing, and methacholine challenge. Eicosanoids were analyzed in EBC by using mass spectrometry and are reported as concentrations (in picograms per milliliter) and eicosanoid/palmitic acid (PA) ratios.
Results |
Eoxin C4/PA, eoxin D4/PA, eoxin E4/PA, 15-HETE/PA, and LTC4/PA ratios were significantly increased in asthmatic versus healthy children. Eoxin D4/PA and LTE4/PA ratios were also significantly higher in children with BHR. A nonsignificant trend was observed toward higher eoxin/PA ratios with increasing asthma severity. In contrast to asthma, children with chronic lung disease had the highest 15-HETE/PA, LTC4/PA, LTE4/PA, and LTB4/PA ratios.
Conclusion |
The results point to increased activity of the 15-LO inflammatory pathway in childhood asthma. Mass spectrometric analyses of EBC demonstrate that increased eoxin levels not only accompany the increased 5-LO product LTC4 but are also associated with BHR. These markers might represent a new therapeutic target for asthma treatment.
El texto completo de este artículo está disponible en PDF.Key words : Exhaled breath condensate, leukotrienes, 15-hydroxyeicosatetraenoic acid, eoxins, asthma, child
Abbreviations used : BAL, BHR, BMI, CysLT, EBC, ECP, FEF25-75, FENO, FVC, HETE, ICS, LO, LT, LTRA, MS, PA, SEARCH
Esquema
| The study was performed within the ORAACLE (Oslo Research Group of Asthma and Allergy in Childhood, the Lung and Environment) and Nordic SEARCH (Severe Asthma Recognized in Childhood) affiliations, both of which are part of the GA2LEN network. The study was supported through the European Economic Area (EEA) financial mechanism. EBC analysis by HPLC–tandem MS has come about as a cooperation project between Norway and Poland sponsored by a Norwegian grant within the framework of the European Community and funds of the Polish Ministry of Science and Higher Education. C. S.-O. has received a research grant from the Kloster foundation, and A. L. has received a research grant from the South Norway Health Region. |
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| Disclosure of potential conflict of interest: C. Sachs-Olsen and A. M. Lang received a fee for scientific lectures from GlaxoSmithKline. M. Sanak, A. Gielicz, and A. Szczeklik have received research support from the European Community and Polish Ministry of Science and Higher Education. K. C. Lødrup Carlsen and K.-H. Carlsen received research support from GA2LEN. P. Mowinckel has declared that he has no conflict of interest. |
Vol 126 - N° 4
P. 859 - octobre 2010 Regresar al número
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