title: Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma.
abstract: BACKGROUND
  A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E(4) (LTE(4)) 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 B(4) (LTB(4)) 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 LTB(4) and the prostaglandin D(2) metabolite 9alpha,11beta-prostaglandin F(2) 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 LTB(4) levels between the groups. Levels of urinary LTE(4) and 9alpha,11beta-prostaglandin F(2) increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit of Experimental Asthma & Allergy Research, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Gaber
authors.forename: K
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authors.lastname: Daham
authors.forename: A
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authors.lastname: Higashi
authors.forename: N
authors.initials: N
authors.lastname: Higashi
authors.forename: A
authors.initials: A
authors.lastname: Gülich
authors.forename: I
authors.initials: I
authors.lastname: Delin
authors.forename: A
authors.initials: A
authors.lastname: James
authors.forename: M
authors.initials: M
authors.lastname: Skedinger
authors.forename: P
authors.initials: P
authors.lastname: Gyllfors
authors.forename: M
authors.initials: M
authors.lastname: Nord
authors.forename: S-E
authors.initials: SE
authors.lastname: Dahlén
authors.forename: M
authors.initials: M
authors.lastname: Kumlin
authors.forename: B
authors.initials: B
authors.lastname: Dahlén