title: Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease.
abstract: BACKGROUND
  Aspirin-exacerbated respiratory disease (AERD) is characterized by respiratory reactions on ingestion of COX-1 inhibitors and cysteinyl leukotriene overproduction. The hypersensitivity reaction is induced by low doses of aspirin that inhibit COX-1 in platelets.
  
  
  OBJECTIVE
  We sought to explore the role of platelets in the pathogenesis of AERD in patients under stable conditions and during an aspirin challenge test.
  
  
  METHODS
  Stable patients with AERD (n = 30), aspirin-tolerant asthma (ATA; n = 21), or idiopathic chronic eosinophilic pneumonia (n = 10) were enrolled. Platelet activation was estimated based on expression levels of P-selectin (CD62P), CD63, CD69, and GPIIb/IIIa (PAC-1) in peripheral platelets; percentages of circulating platelet-adherent leukocytes; and plasma levels of soluble P-selectin (sP-selectin) and soluble CD40 ligand (sCD40L).
  
  
  RESULTS
  In the stable condition, expression of all surface markers on platelets, the percentage of platelet-adherent eosinophils, and the plasma levels of sP-selectin and sCD40L were significantly higher in patients with AERD compared with those in patients with ATA. P-selectin and CD63 expression on platelets and plasma sP-selectin and sCD40L levels were positively correlated with the percentage of platelet-adherent eosinophils. Among these markers, P-selectin expression and plasma sP-selectin levels positively correlated with urinary concentrations of leukotriene E4. Additionally, plasma sP-selectin and sCD40L levels were negatively correlated with lung function. In contrast, platelet activation markers in patients with AERD did not change during the aspirin challenge test.
  
  
  CONCLUSIONS
  Peripheral platelets were activated more in patients with stable AERD compared with those in patients with stable ATA, patients with idiopathic chronic eosinophilic pneumonia, and control subjects. Platelet activation was involved in cysteinyl leukotriene overproduction and persistent airflow limitations in patients with AERD.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan; Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mitsui
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kajiwara
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ito
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Mita
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Ono
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan; Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Higashi
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Fukutomi
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sekiya
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsuburai
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Akiyama
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan. Electronic address: m-taniguchi@sagamihara-hosp.gr.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D055963:Asthma, Aspirin-Induced / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism; D015897:Comorbidity; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D017999:Leukotriene E4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000235:genetics* / Q000276:immunology*; D012120:Respiration Disorders / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D017999:Leukotriene E4; D001241:Aspirin
keywords: P-selectin; adhesion; aspirin-exacerbated respiratory disease; asthma; cysteinyl leukotriene; platelet