title: Systemic expression of inflammatory mediators in patients with chronic rhinosinusitis and nasal polyps with and without Aspirin Exacerbated Respiratory Disease.
abstract: BACKGROUND
  Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD.
  
  
  METHODS
  Patients with nasal polyposis and asthma with AERD (n=20) and without (n=18) were orally challenged with aspirin in a single-blind placebo controlled study. Serum samples and urine were collected before and 6h after placebo and aspirin oral challenges. Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA. The concentrations of 9-alpha, 11-beta prostaglandin F2, and leukotriene E4 (uLTE4) were measured in urine samples by ELISA. The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges.
  
  
  RESULTS
  AERD patients showed significantly higher baseline levels of s-IL-5R-alpha, uLTE4 and percentage of CD4(+)CD25(+)CD127(pos) and CD4(+)CD45RA(-)CD45RO(+) but decreased levels of TGF-β1 and number of CD4(+)CD25(+)CD127(neg) cells. Aspirin challenge induced the release of uLTE4, IL-6 and increased the number of CD4(+)CD45RA(-)CD45RO(+) memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects. Further, IL-8 and sIL-5R-alpha levels directly correlated with the PD20ASA and the effects of aspirin on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction (bronchial and nasal).
  
  
  CONCLUSIONS
  AERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease. Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients.
authors.affiliation: Upper Airways Research Laboratory, Dept. of Otorhinolaryngology, Ghent University Hospital, Belgium; Dept. of Otorhinolaryngology, Head and Neck Surgery, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Rogerio
authors.initials: R
authors.lastname: Pezato
authors.affiliation: Out-patient Allergy Clinic, Medex, Bielsko-Biała, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Świerczyńska-Krępa
authors.affiliation: Dept. of Medicine, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Niżankowska-Mogilnicka
authors.affiliation: Upper Airways Research Laboratory, Dept. of Otorhinolaryngology, Ghent University Hospital, Belgium.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Holtappels
authors.affiliation: Upper Airways Research Laboratory, Dept. of Otorhinolaryngology, Ghent University Hospital, Belgium.
authors.forename: Natalie
authors.initials: N
authors.lastname: De Ruyck
authors.affiliation: Dept. of Medicine, Jagiellonian University School of Medicine, Cracow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Sanak
authors.affiliation: Upper Airways Research Laboratory, Dept. of Otorhinolaryngology, Ghent University Hospital, Belgium.
authors.forename: Lara
authors.initials: L
authors.lastname: Derycke
authors.affiliation: Upper Airways Research Laboratory, Dept. of Otorhinolaryngology, Ghent University Hospital, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Crombruggen
authors.affiliation: Upper Airways Research Laboratory, Dept. of Otorhinolaryngology, Ghent University Hospital, Belgium.
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
authors.affiliation: Upper Airways Research Laboratory, Dept. of Otorhinolaryngology, Ghent University Hospital, Belgium. Electronic address: Claudina.Pereznovo@UGent.be.
authors.forename: Claudina A
authors.initials: CA
authors.lastname: Pérez-Novo
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D055963:Asthma, Aspirin-Induced / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000032:analysis* / Q000097:blood / Q000652:urine; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000652:urine; D012220:Rhinitis / Q000378:metabolism*; D016037:Single-Blind Method; D012852:Sinusitis / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018836:Inflammation Mediators; D017999:Leukotriene E4; D001241:Aspirin; D015230:Prostaglandin D2
keywords: Aspirin Exacerbated Respiratory Disease; IL-5 receptor alpha; Interleukin 6; Interleukin 8; Memory T-cells; Oral aspirin challenge; Systemic reaction after aspirin challenge; TGF-β(1)