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2012 Fiscal Year Final Research Report

Pulmonary Alveolar Proteinosis (PAP) and Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Therapy--ClinicalFeatures Predicting Response and Recurrence.

Research Project

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Project/Area Number 22590852
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNiigata University

Principal Investigator

TAZAWA Ryushi  新潟大学, 医歯学総合病院, 講師 (70301041)

Co-Investigator(Kenkyū-buntansha) NAKATA Koh  新潟大学, 医歯学総合病院, 教授 (80207802)
Research Collaborator SUZUKI Takuji  シンシナテイ小児病院医療センター, 研究員
Project Period (FY) 2010 – 2012
Keywords肺胞蛋白症 / 吸入治療 / GM-CSF / 自己抗体 / バイオマーカー / 気管支肺胞洗浄
Research Abstract

Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. To figure out predictive and prognostic factors for GM-CSF inhalation therapy in aPAP, we performed retrospective analyses of BALF obtained in aPAP patients before and after GM-CSF inhalation therapy. We confirmed that GM-CSF inhalation was associated with a decrease of GM-Ab in the BALF in improved lungs, which was probably due to the restoration of clearance, and that GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleuki-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis. Furthermore, through the post-treatment, 30-month observation, we concluded that inhaled GM-CSF therapy sustained remission in more than half of cases, and baseline %VC might be a prognostic factor for disease recurrence.

  • Research Products

    (21 results)

All 2013 2012 2011 2010 Other

All Journal Article (11 results) (of which Peer Reviewed: 10 results) Presentation (5 results) Book (4 results) Remarks (1 results)

  • [Journal Article] Bilateral peripheral infiltrates refractory to immunosuppressants were diagnosed as autoimmune pulmonary alveolar proteinosis and improved by inhalation of granulocyte/macrophage- colony stimulating factor2012

    • Author(s)
      Satoh H, Tazawa R, Sakakibara T, Ohkouchi S, Ebina M, Miki M, Nakata K, Nukiwa T
    • Journal Title

      Intern Med

      Volume: 51(13) Pages: 1737-42

    • Peer Reviewed
  • [Journal Article] Runx1 deficiency in CD4+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells2012

    • Author(s)
      Wong WF, Kohu K, Nakamura A, Ebina M, Kikuchi T, Tazawa R, Tanaka K, Kon S, Funaki T, Sugahara-Tobinai A, Looi CY, Endo S, Funayama R, Kurokawa M, Habu S, Ishii N, Fukumoto M, Nakata K, Takai T, Satake M
    • Journal Title

      J Immunol

      Volume: 188(11) Pages: 5408-20

    • Peer Reviewed
  • [Journal Article] Reduced GM-CSF autoantibody in improved lung of autoimmune pulmonary alveolar proteinosis2012

    • Author(s)
      Ohashi K, Sato A, Takada T, Arai T, Kasahara Y, Hojo M, Nei T, Nakayama H, Motoi N, Urano S, Eda R, Yokoba M, Tsuchihashi Y, Nasuhara Y, Ishii H, Ebina M, Yamaguchi E, Inoue Y, Nakata K, Tazawa R
    • Journal Title

      Eur Respir J

      Volume: 39(3) Pages: 777-80

    • Peer Reviewed
  • [Journal Article] IgM-type GM-CSF autoantibody is etiologically a bystander but associated with IgG-type autoantibody production in autoimmune pulmonary alveolar proteinosis2012

    • Author(s)
      Nei T, Urano S, Motoi N, Takizawa J, Kaneko C, Kanazawa H, Tazawa R, Nakagaki K, Akagawa KS, Akasaka K, Ichiwata T, Azuma A, Nakata K
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol

      Volume: 302(9) Pages: L959-64

    • Peer Reviewed
  • [Journal Article] Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis2012

    • Author(s)
      Ohashi K, Sato A, Takada T, Arai T, Nei T, Kasahara Y, Motoi N, Hojo M, Urano S, Ishii H, Yokoba M, Eda R, Nakayama H, Nasuhara Y, Tsuchihashi Y, Kaneko C, Kanazawa H, Ebina M, Yamaguchi E, Kirchner J, Inoue Y, Nakata K, Tazawa R
    • Journal Title

      Respir Med

      Volume: 106(2) Pages: 284-93

    • Peer Reviewed
  • [Journal Article] A cell free assay system estimating the neutralizing capacity of GM-CSF antibody using recombinant soluble GM-CSF receptor2011

    • Author(s)
      Urano S, Tazawa R, Nei T, Motoi N, Watanabe M, Igarashi T, Tomita M, Nakata K
    • Journal Title

      J Vis Exp

      Volume: (52) Pages: pii:2742

    • Peer Reviewed
  • [Journal Article] Clinical features of secondary pulmonary alveolar proteinosis: pre-mortem cases in Japan2011

    • Author(s)
      Ishii H, Tazawa R, Kaneko C, Saraya T, Inoue Y, Hamano E, Kogure Y, Tomii K, Terada M, Takada T, Hojo M, Nishida A, Ichiwata T, Trapnell BC, Goto H, Nakata K
    • Journal Title

      Eur Respir J

      Volume: 37(2) Pages: 465-8

    • Peer Reviewed
  • [Journal Article] Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB2011

    • Author(s)
      Tanaka T, Motoi N, Tsuchihashi Y, Tazawa R, Kaneko C, Nei T, Yamamoto T, Hayashi T, Tagawa T, Nagayasu T, Kuribayashi F,Ariyoshi K, Nakata K, Morimoto K
    • Journal Title

      J Med Genet

      Volume: 48(3) Pages: 205-9

    • Peer Reviewed
  • [Journal Article] A cell-free assay to estimate the neutralizing capacity of granulocyte-macrophage colony-stimulating factor autoantibodies2010

    • Author(s)
      Urano S, Kaneko C, Nei T, Motoi N, Tazawa R, Watanabe M, Tomita M, Adachi T, Kanazawa H, Nakata K
    • Journal Title

      J Immunol Methods

      Volume: 360(1-2) Pages: 141-8

    • Peer Reviewed
  • [Journal Article] Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis2010

    • Author(s)
      Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, Hizawa N, Kasahara Y, Tatsumi K, Hojo M, Ishii H, Yokoba M, Tanaka N, Yamaguchi E, Eda R, Tsuchihashi Y, Morimoto K, Akira M, Terada M, Otsuka J, Ebina M, Kaneko C, Nukiwa T, Krischer JP, Akazawa K, Nakata K
    • Journal Title

      Am J Respir Crit Care Med

      Volume: 181 Pages: 1345-54

    • Peer Reviewed
  • [Journal Article] 呼吸器領域の新しい薬物療法肺胞蛋白症薬GM-CSF製剤2010

    • Author(s)
      田澤立之,中田光
    • Journal Title

      日本内科学会雑誌

      Volume: 第99巻7号 Pages: 1623-1627

  • [Presentation] Pulmonary Alveolar Proteinosis (PAP) And Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Therapy--Clinical Features Predicting Recurrence2012

    • Author(s)
      Ryushi Tazawa, Toru Arai, Toshinori Takada, Yasunori Kasahara, Yoshiko Tsuchihashi, Takahito Nei, Masayuki Hojo, Hideaki Nakayama, Masanori Yokoba, Shinya Ohkouchi, Haruyuki Ishii, Ryosuke Eda, Yasuyuki Nasuhara, Masahito Ebina, Masanori Akira, Etsuro Yamaguchi, Yoshikazu Inoue, and Koh Nakata
    • Organizer
      Am. J. Respir. Crit. Care Med
    • Year and Date
      2012-05-23
  • [Presentation] Prognosis Of Secondary Pulmonary Alveolar Proteinosis Complicated With Myelodysplastic Syndrome: 28 Cases In Japan2012

    • Author(s)
      Haruyuki Ishii, Ryushi Tazawa, Yoshikazu Inoue, and Koh Nakata
    • Organizer
      Am. J. Respir. Crit. Care Med
    • Year and Date
      2012-05-23
  • [Presentation] EffectOf Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Inhalation On Bronchoalveolar Lavage Fluid And Serum In Pulmonary Alveolar Proteinosis2011

    • Author(s)
      Ryushi Tazawa, Kazumasa Ohashi, Atsuyasu Sato, Toru Arai, Yasunori Kasahara, Masayuki Hojo, Masanori Yokoba, Yoshiko Tsuchihashi, Haruyuki Ishii, Yasuyuki Nasuhara, Masahito Ebina, Toshinori Takada, Etsuro Yamaguchi, Yoshikazu Inoue, and Koh Nakata
    • Organizer
      Am. J. Respir. Crit. Care Med
    • Year and Date
      2011-05-15
  • [Presentation] Trapnell. A Multicenter, International Evaluation Of Blood Testing For The Diagnosis Of Autoimmune Pulmonary Alveolar Proteinosis2011

    • Author(s)
      Brenna Carey, Kanji Uchida, Koh Nakata, Ryushi Tazawa, Yoshikazu Inoue, Masaki Hirose, Mani S. Kavuru, Mary J. Thomassen, Maurizio Luisetti, Francesca Mariani, Ilaria Campo, Ulrich Costabel, Francesco Bonella, Rhonda Vandyke, Claudia Chalk, and Bruce C
    • Organizer
      Am. J. Respir. Crit. Care Med
    • Year and Date
      2011-05-15
  • [Presentation] Characterization Of Bronchoalveolar Lavage Fluid During Granulocyte- macrophage Colony-stimulating Factor Inhalation In Patients With Autoimmune Pulmonary Alveolar Proteinosis2010

    • Author(s)
      Ryushi Tazawa, Kazumasa Ohashi, Atsuyasu Sato, Yoshikazu Inoue, Masanori Akira, Masaki Terada, Hideaki Nakayama, Toshinori Takada, and Koh Nakata
    • Organizer
      Am. J. Respir. Crit. Care Med
    • Year and Date
      2010-05-17
  • [Book] 肺胞蛋白症.貫和敏博,杉山幸比古,門田淳一編「呼吸器疾患最新の治療2013-2015」2013

    • Author(s)
      田澤立之(分担執筆)
    • Total Pages
      331-333
    • Publisher
      南江堂,東京
  • [Book] 肺胞蛋白症.山口徹,北原光夫,福井次矢編「今日の治療指針2013年版」2013

    • Author(s)
      田澤立之(分担執筆)
    • Total Pages
      311-312
    • Publisher
      医学書院,東京
  • [Book] 臨床研究の審査,肺ランゲルハンス細胞組織球症.萩原弘一編「呼吸器研修ノート」2011

    • Author(s)
      田澤立之(分担執筆)
    • Total Pages
      485 614-616
    • Publisher
      診断と治療社
  • [Book] 肺胞蛋白症の治療最近の進歩.永井厚志,巽浩一郎,桑野和善,高橋和久編「Annual Review呼吸器2010」2010

    • Author(s)
      田澤立之,中田光(分担執筆)
    • Total Pages
      219-223
    • Publisher
      中外医学社,東京
  • [Remarks]

    • URL

      http://www.pap-guide.jp/about/cure.html#03

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Published: 2014-08-29  

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