title: Challenge of isolated sputum cells supports in vivo origin of intolerance reaction to aspirin/non-steroidal anti-inflammatory drugs in asthma.
abstract: BACKGROUND
  There is no in vitro test to diagnose aspirin-intolerant asthma (AIA). The aim of this study was to test if challenge with aspirin of sputum cells from subjects with AIA triggers the release of cysteinyl leukotrienes (CysLTs), known to be mediators of bronchoconstriction in AIA.
  
  
  METHODS
  Sputum induction was performed at baseline and at another visit 2 h after a lysine-aspirin bronchoprovocation in 10 subjects with AIA and 9 subjects with aspirin-tolerant asthma (ATA). The isolated sputum cells were incubated for ex vivo challenge.
  
  
  RESULTS
  Release of CysLTs by sputum cells from patients with AIA was not induced by lysine-aspirin ex vivo, neither when cells were collected at baseline nor in sputum cells recovered after lysine-aspirin-induced bronchoconstriction, whereas release of CysLTs from sputum cells was triggered by an ionophore on both occasions. However, the CysLT levels elicited by the ionophore were higher in the AIA group both at baseline (AIA vs. ATA: 3.3 vs. 1.6 ng/million cells; p < 0.05) and after the lysine-aspirin bronchoprovocation (3.9 vs. 1.7 ng/million cells; p < 0.05). This difference in the amount of CysLTs released between the groups appeared to be related to the number of eosinophils.
  
  
  CONCLUSIONS
  Intolerance to aspirin could not be triggered in sputum cells isolated from subjects with AIA. Together with the previous inability to demonstrate intolerance to non-steroidal anti-inflammatory drugs in isolated blood cells, these results support the requirement of tissue-resident cells in the adverse reaction. However, ex vivo stimulation of sputum cells may be developed into a new test of capacity for LT release in inflammatory cells recovered from airways.
authors.affiliation: Unit of Experimental Asthma and Allergy Research, The National Institute of Environmental Medicine, Stockholm, Sweden.
authors.forename: Ai
authors.initials: A
authors.lastname: Higashi
authors.forename: Maria
authors.initials: M
authors.lastname: Kumlin
authors.forename: Noritaka
authors.initials: N
authors.lastname: Higashi
authors.forename: Kameran
authors.initials: K
authors.lastname: Daham
authors.forename: Flora
authors.initials: F
authors.lastname: Gaber
authors.forename: Agneta
authors.initials: A
authors.lastname: Lindeberg
authors.forename: Anna
authors.initials: A
authors.lastname: James
authors.forename: Maria
authors.initials: M
authors.lastname: Skedinger
authors.forename: Ingrid
authors.initials: I
authors.lastname: Delin
authors.forename: Pär
authors.initials: P
authors.lastname: Gyllfors
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000276:immunology; D055963:Asthma, Aspirin-Induced / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D001491:Basophils / Q000166:cytology / Q000276:immunology; D001760:Bleeding Time; D003545:Cysteine / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000209:etiology / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000166:cytology* / Q000276:immunology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D003545:Cysteine; D001241:Aspirin