title: Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin-hypersensitive asthmatics.
abstract: BACKGROUND
  Isoprostanes are bioactive compounds formed by non-enzymatic oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free radical generation during inflammation. In aspirin exacerbated respiratory disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1 isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is accompanied by changes of isoprostanes in exhaled breath condensate (EBC).
  
  
  METHODS
  EBC was collected from 28 AERD subjects and 25 aspirin-tolerant asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso-PGF2α, 8-iso-PGE2, and prostaglandin E2 were measured using gas chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in urine samples collected before and after the challenge.
  
  
  RESULTS
  Before the challenge, exhaled 8-iso-PGF2α, 8-iso-PGE2, and PGE2 levels did not differ between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014) as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated positively with urinary LTE4 level (p=0.046), whereas it correlated negatively with the provocative dose of aspirin (p=0.027).
  
  
  CONCLUSIONS
  A significant increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was selective and not present for the other isoprostane measured. This is a novel finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso-PGE2 production in a specific mechanism, contributing to bronchoconstriction and systemic overproduction of cysteinyl leukotrienes.
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Mastalerz
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Januszek
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kaszuba
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wójcik
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Celejewska-Wójcik
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gielicz
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Plutecka
authors.affiliation: Department of Otolaryngology, Jagiellonian University School of Medicine, Śniadeckich 2, 31-531 Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Oleś
authors.affiliation: Department of Otolaryngology, Jagiellonian University School of Medicine, Śniadeckich 2, 31-531 Kraków, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Stręk
authors.affiliation: Department of Medicine, Jagiellonian University School of Medicine, Skawińska 8, 31-066 Kraków, Poland. Electronic address: nfsanak@cyf-kr.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001241:Aspirin / Q000031:analogs & derivatives* / Q000633:toxicity; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology; D055963:Asthma, Aspirin-Induced / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism / Q000652:urine; D001944:Breath Tests; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D015232:Dinoprostone / Q000819:agonists / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D028421:Isoprostanes / Q000819:agonists* / Q000032:analysis / Q000378:metabolism; D017999:Leukotriene E4 / Q000037:antagonists & inhibitors / Q000652:urine; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012720:Severity of Illness Index; D016037:Single-Blind Method
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D028421:Isoprostanes; D017999:Leukotriene E4; D008239:Lysine; D015232:Dinoprostone; D001241:Aspirin; C011987:8-isoprostaglandin E2; C010395:acetylsalicylic acid lysinate
keywords: Aspirin challenge; Aspirin exacerbated respiratory disease; Cysteinyl leukotrienes; Exhaled breath condensate; Isoprostanes