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Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from aspirin-intolerant asthmatics
  1. Flora Gaber (flora.gaber{at}ki.se)
  1. Karolinska Institutet, Sweden
    1. Kameran Daham (kameran.daham{at}ki.se)
    1. Karolinska University Hospital, Sweden
      1. Ai Higashi (chocolat_au_leit{at}yahoo.co.jp)
      1. Karolinska Institutet, Sweden
        1. Noritaka Higashi (nonta4511{at}yahoo.co.jp)
        1. Karolinska Institutet, Sweden
          1. Agneta Gulich (agneta.gulich{at}karolinska.se)
          1. Karolinska University Hospital, Sweden
            1. Ingrid Delin (ingrid.delin{at}ki.se)
            1. Karolinska Institutet, Sweden
              1. Anna James (anna.james{at}imm.ki.se)
              1. Karolinska Institutet and Karolinska University Hospital, Sweden
                1. Maria Skedinger (maria.skedinger{at}karolinska.se)
                1. Karolinska University Hospital, Sweden
                  1. Pär Gyllfors (par.gyllfors{at}astmaallergi.stgoran.se)
                  1. Karolinska University Hospital, Sweden
                    1. Magnus Nord (magnus.nord{at}ki.se)
                    1. Karolinska University Hospital, Sweden
                      1. Sven-Erik Dahlén (sven-erik.dahlen{at}ki.se)
                      1. Karolinska Institutet, Sweden
                        1. Maria Kumlin (maria.kumlin{at}ki.se)
                        1. Karolinska Institutet, Sweden
                          1. Barbro Dahlén (barbro.dahlen{at}ki.se)
                          1. Karolinska University Hospital, Sweden

                            Abstract

                            Background: Diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E4 is elevated in aspirin-intolerant asthma.

                            Objective: New biomarkers of aspirin-intolerance were investigated by comparing basal levels of cysteinyl-leukotrienes and leukotriene B4 in saliva, sputum, and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of aspirin- and allergen-induced bronchoconstriction on leukotriene levels in saliva and ex vivo stimulated blood were also compared with the effects of the provocations on urinary mediators.

                            Methods: Induced sputum, saliva, urine and blood were obtained at baseline in 21 subjects with asthma. At a separate visit, eleven subjects showed a positive response to lysine-aspirin inhalation whereas ten were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of cysteinyl-leukotrienes and leukotriene B4 and the prostaglandin D2 metabolite 9α,11β-prostaglandin F2 were performed and the fraction of exhaled nitric oxide was measured.

                            Results: Subjects with aspirin-intolerant asthma had higher exhaled nitric oxide levels and higher baseline levels of cysteinyl-leukotrienes in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in leukotriene B4 between the groups. Levels of urinary leukotriene E4, and 9α,11β-prostaglandin F2 increased after aspirin provocation, whereas leukotriene levels in saliva and ex vivo stimulated blood were not increased post challenge.

                            Conclusion: The findings support a global and specific exaggeration of cysteinyl-leukotriene production in aspirin-intolerant asthma. Measurement of cysteinyl-leukotrienes in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.

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