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Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma
  1. F Gaber1,
  2. K Daham2,
  3. A Higashi1,
  4. N Higashi1,
  5. A Gülich2,
  6. I Delin1,
  7. A James1,2,
  8. M Skedinger2,
  9. P Gyllfors2,
  10. M Nord3,
  11. S-E Dahlén1,
  12. M Kumlin1,4,
  13. B Dahlén2
  1. 1
    Unit of Experimental Asthma & Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, Sweden
  2. 2
    Division of Respiratory Medicine and Allergy, Department of Medicine, Karolinska University Hospital, Huddinge, Sweden
  3. 3
    Department of Medicine, Karolinska University Hospital, Solna, Sweden
  4. 4
    Sophiahemmet University College, Stockholm, Sweden; all partners at Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
  1. Dr B Dahlén, Lung and Allergy Clinic, MS3, Karolinska University Hospital, SE-141 86 Stockholm, Sweden; Barbro.dahlen{at}


Background: A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E4 (LTE4) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B4 (LTB4) 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 from 21 subjects with asthma. At a separate visit, 11 subjects showed a positive response to lysine-aspirin inhalation and 10 were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of CysLTs and LTB4 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 CysLTs in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in LTB4 levels between the groups. Levels of urinary LTE4 and 9α,11β-prostaglandin F2 increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase.

Conclusion: These findings support a global and specific increase in CysLT production in aspirin-intolerant asthma. Measurement of CysLTs in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.

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  • ▸ An extended version of the Methods section is published online only at

  • Funding: The Swedish MRC, Heart-Lung Foundation, Asthma and Allergy Foundation, The Stockholm County Council (ALF), the Research Council of HMQ Sophiahemmet and Karolinska Institutet.

  • Competing interests: None.

  • Ethics approval: The study was approved by the local ethics committee (Dnr 518/03) and the subjects gave written informed consent.

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