Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease
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 expl...
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| Veröffentlicht in: | Journal of allergy and clinical immunology 2016-02, Vol.137 (2), p.400-411 |
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| creator | Mitsui, Chihiro, MD Kajiwara, Keiichi, BSc Hayashi, Hiroaki, MD Ito, Jun, MD, PhD Mita, Haruhisa, PhD Ono, Emiko, MD, PhD Higashi, Noritaka, MD, PhD Fukutomi, Yuma, MD, PhD Sekiya, Kiyoshi, MD Tsuburai, Takahiro, MD, PhD Akiyama, Kazuo, MD Yamamoto, Kazuhiko, MD, PhD Taniguchi, Masami, MD, PhD |
| description | 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. Conclusion 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. |
| doi_str_mv | 10.1016/j.jaci.2015.05.041 |
| format | Article |
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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. Conclusion 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.</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2015.05.041</identifier><identifier>PMID: 26194538</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>adhesion ; Adult ; Aged ; Allergy and Immunology ; Anti-Inflammatory Agents, Non-Steroidal - adverse effects ; Aspirin ; Aspirin - adverse effects ; aspirin-exacerbated respiratory disease ; Asthma ; Asthma, Aspirin-Induced - diagnosis ; Asthma, Aspirin-Induced - genetics ; Asthma, Aspirin-Induced - immunology ; Asthma, Aspirin-Induced - metabolism ; Asthma, Aspirin-Induced - physiopathology ; Biomarkers ; Blood platelets ; Blood Platelets - immunology ; Blood Platelets - metabolism ; Comorbidity ; cysteinyl leukotriene ; Drug dosages ; Female ; Flow cytometry ; Gene Expression ; Humans ; Immunophenotyping ; Inflammation ; Leukotriene E4 - metabolism ; Ligands ; Lymphocytes ; Male ; Middle Aged ; Neutrophils ; Nonsteroidal anti-inflammatory drugs ; P-selectin ; Pathogenesis ; platelet ; Platelet Activation - genetics ; Platelet Activation - immunology ; Respiration Disorders - diagnosis ; Respiration Disorders - etiology ; Respiration Disorders - metabolism ; Respiration Disorders - physiopathology ; Risk Factors</subject><ispartof>Journal of allergy and clinical immunology, 2016-02, Vol.137 (2), p.400-411</ispartof><rights>American Academy of Allergy, Asthma & Immunology</rights><rights>2015 American Academy of Allergy, Asthma & Immunology</rights><rights>Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c586t-56e78fa81706bd891c441c73af7a538430fadf7aba12a8c723a405326d8e69243</citedby><cites>FETCH-LOGICAL-c586t-56e78fa81706bd891c441c73af7a538430fadf7aba12a8c723a405326d8e69243</cites><orcidid>0000-0003-1762-0719</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jaci.2015.05.041$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26194538$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mitsui, Chihiro, MD</creatorcontrib><creatorcontrib>Kajiwara, Keiichi, BSc</creatorcontrib><creatorcontrib>Hayashi, Hiroaki, MD</creatorcontrib><creatorcontrib>Ito, Jun, MD, PhD</creatorcontrib><creatorcontrib>Mita, Haruhisa, PhD</creatorcontrib><creatorcontrib>Ono, Emiko, MD, PhD</creatorcontrib><creatorcontrib>Higashi, Noritaka, MD, PhD</creatorcontrib><creatorcontrib>Fukutomi, Yuma, MD, PhD</creatorcontrib><creatorcontrib>Sekiya, Kiyoshi, MD</creatorcontrib><creatorcontrib>Tsuburai, Takahiro, MD, PhD</creatorcontrib><creatorcontrib>Akiyama, Kazuo, MD</creatorcontrib><creatorcontrib>Yamamoto, Kazuhiko, MD, PhD</creatorcontrib><creatorcontrib>Taniguchi, Masami, MD, PhD</creatorcontrib><title>Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>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. Conclusion 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.</description><subject>adhesion</subject><subject>Adult</subject><subject>Aged</subject><subject>Allergy and Immunology</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</subject><subject>Aspirin</subject><subject>Aspirin - adverse effects</subject><subject>aspirin-exacerbated respiratory disease</subject><subject>Asthma</subject><subject>Asthma, Aspirin-Induced - diagnosis</subject><subject>Asthma, Aspirin-Induced - genetics</subject><subject>Asthma, Aspirin-Induced - immunology</subject><subject>Asthma, Aspirin-Induced - metabolism</subject><subject>Asthma, Aspirin-Induced - physiopathology</subject><subject>Biomarkers</subject><subject>Blood platelets</subject><subject>Blood Platelets - immunology</subject><subject>Blood Platelets - metabolism</subject><subject>Comorbidity</subject><subject>cysteinyl leukotriene</subject><subject>Drug dosages</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Inflammation</subject><subject>Leukotriene E4 - metabolism</subject><subject>Ligands</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neutrophils</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>P-selectin</subject><subject>Pathogenesis</subject><subject>platelet</subject><subject>Platelet Activation - genetics</subject><subject>Platelet Activation - immunology</subject><subject>Respiration Disorders - diagnosis</subject><subject>Respiration Disorders - etiology</subject><subject>Respiration Disorders - metabolism</subject><subject>Respiration Disorders - physiopathology</subject><subject>Risk Factors</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkkuLFDEUhYMoTk_rH3AhATduqs2r8gARhsFRYUBBXYd06hamprpSJul2-t-bskeFWYgQyIPvHHLvuQg9o2RDCZWvhs3gfNgwQtsNqUvQB2hFiVGN1Kx9iFaEGNpIJcwZOs95IPXOtXmMzpikRrRcr1D8NLoCIxTsfAkHV0Kc8M6lG0gZxwMkuJ0T5AwdzjP40AfvxvGIw4TnCsNUMv4Ryjfs8hxSmBq4dR7Stpp2uArroysxHXEXMrgMT9Cj3o0Znt7ta_T16u2Xy_fN9cd3Hy4vrhvfalmaVoLSvdNUEbnttKFeCOoVd71y9d-Ck9519bx1lDntFeNOkJYz2WmQhgm-Ri9PvnOK3_eQi92F7GEc3QRxny1VsjVGUMX_BxWUK9PKir64hw5xn6ZayEJxQrSu6BqxE-VTzDlBb-cUak-PlhK7JGcHuyRnl-QsqeuX6Pmd9X67g-6P5HdUFXh9AqC27RAg2exr_z10IYEvtovh3_5v7sn9GKYlzRs4Qv5bh83MEvt5mZ1ldGhLSK2d8Z8pBb_p</recordid><startdate>20160201</startdate><enddate>20160201</enddate><creator>Mitsui, Chihiro, MD</creator><creator>Kajiwara, Keiichi, BSc</creator><creator>Hayashi, Hiroaki, MD</creator><creator>Ito, Jun, MD, PhD</creator><creator>Mita, Haruhisa, PhD</creator><creator>Ono, Emiko, MD, PhD</creator><creator>Higashi, Noritaka, MD, PhD</creator><creator>Fukutomi, Yuma, MD, PhD</creator><creator>Sekiya, Kiyoshi, MD</creator><creator>Tsuburai, Takahiro, MD, PhD</creator><creator>Akiyama, Kazuo, MD</creator><creator>Yamamoto, Kazuhiko, MD, PhD</creator><creator>Taniguchi, Masami, MD, PhD</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1762-0719</orcidid></search><sort><creationdate>20160201</creationdate><title>Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease</title><author>Mitsui, Chihiro, MD ; Kajiwara, Keiichi, BSc ; Hayashi, Hiroaki, MD ; Ito, Jun, MD, PhD ; Mita, Haruhisa, PhD ; Ono, Emiko, MD, PhD ; Higashi, Noritaka, MD, PhD ; Fukutomi, Yuma, MD, PhD ; Sekiya, Kiyoshi, MD ; Tsuburai, Takahiro, MD, PhD ; Akiyama, Kazuo, MD ; Yamamoto, Kazuhiko, MD, PhD ; Taniguchi, Masami, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c586t-56e78fa81706bd891c441c73af7a538430fadf7aba12a8c723a405326d8e69243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>adhesion</topic><topic>Adult</topic><topic>Aged</topic><topic>Allergy and Immunology</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - adverse effects</topic><topic>Aspirin</topic><topic>Aspirin - adverse effects</topic><topic>aspirin-exacerbated respiratory disease</topic><topic>Asthma</topic><topic>Asthma, Aspirin-Induced - diagnosis</topic><topic>Asthma, Aspirin-Induced - genetics</topic><topic>Asthma, Aspirin-Induced - immunology</topic><topic>Asthma, Aspirin-Induced - metabolism</topic><topic>Asthma, Aspirin-Induced - physiopathology</topic><topic>Biomarkers</topic><topic>Blood platelets</topic><topic>Blood Platelets - immunology</topic><topic>Blood Platelets - metabolism</topic><topic>Comorbidity</topic><topic>cysteinyl leukotriene</topic><topic>Drug dosages</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Inflammation</topic><topic>Leukotriene E4 - metabolism</topic><topic>Ligands</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neutrophils</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>P-selectin</topic><topic>Pathogenesis</topic><topic>platelet</topic><topic>Platelet Activation - genetics</topic><topic>Platelet Activation - immunology</topic><topic>Respiration Disorders - diagnosis</topic><topic>Respiration Disorders - etiology</topic><topic>Respiration Disorders - metabolism</topic><topic>Respiration Disorders - physiopathology</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mitsui, Chihiro, MD</creatorcontrib><creatorcontrib>Kajiwara, Keiichi, BSc</creatorcontrib><creatorcontrib>Hayashi, Hiroaki, MD</creatorcontrib><creatorcontrib>Ito, Jun, MD, PhD</creatorcontrib><creatorcontrib>Mita, Haruhisa, PhD</creatorcontrib><creatorcontrib>Ono, Emiko, MD, PhD</creatorcontrib><creatorcontrib>Higashi, Noritaka, MD, PhD</creatorcontrib><creatorcontrib>Fukutomi, Yuma, MD, PhD</creatorcontrib><creatorcontrib>Sekiya, Kiyoshi, MD</creatorcontrib><creatorcontrib>Tsuburai, Takahiro, MD, PhD</creatorcontrib><creatorcontrib>Akiyama, Kazuo, MD</creatorcontrib><creatorcontrib>Yamamoto, Kazuhiko, MD, PhD</creatorcontrib><creatorcontrib>Taniguchi, Masami, MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mitsui, Chihiro, MD</au><au>Kajiwara, Keiichi, BSc</au><au>Hayashi, Hiroaki, MD</au><au>Ito, Jun, MD, PhD</au><au>Mita, Haruhisa, PhD</au><au>Ono, Emiko, MD, PhD</au><au>Higashi, Noritaka, MD, PhD</au><au>Fukutomi, Yuma, MD, PhD</au><au>Sekiya, Kiyoshi, MD</au><au>Tsuburai, Takahiro, MD, PhD</au><au>Akiyama, Kazuo, MD</au><au>Yamamoto, Kazuhiko, MD, PhD</au><au>Taniguchi, Masami, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>137</volume><issue>2</issue><spage>400</spage><epage>411</epage><pages>400-411</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><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. Conclusion 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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26194538</pmid><doi>10.1016/j.jaci.2015.05.041</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-1762-0719</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | adhesion Adult Aged Allergy and Immunology Anti-Inflammatory Agents, Non-Steroidal - adverse effects Aspirin Aspirin - adverse effects aspirin-exacerbated respiratory disease Asthma Asthma, Aspirin-Induced - diagnosis Asthma, Aspirin-Induced - genetics Asthma, Aspirin-Induced - immunology Asthma, Aspirin-Induced - metabolism Asthma, Aspirin-Induced - physiopathology Biomarkers Blood platelets Blood Platelets - immunology Blood Platelets - metabolism Comorbidity cysteinyl leukotriene Drug dosages Female Flow cytometry Gene Expression Humans Immunophenotyping Inflammation Leukotriene E4 - metabolism Ligands Lymphocytes Male Middle Aged Neutrophils Nonsteroidal anti-inflammatory drugs P-selectin Pathogenesis platelet Platelet Activation - genetics Platelet Activation - immunology Respiration Disorders - diagnosis Respiration Disorders - etiology Respiration Disorders - metabolism Respiration Disorders - physiopathology Risk Factors |
| title | Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease |
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