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How GM-CSF inhalation improves clinical and biological factors in pulmonary alveolar proteinosis?

Research Project

Project/Area Number 25461153
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
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, 准教授 (70301041)

Co-Investigator(Kenkyū-buntansha) Nakata Koh  新潟大学, 医歯学総合病院, 教授 (80207802)
Ishii Haruyuki  杏林大学, 医学部呼吸器内科, 准教授 (30406970)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺胞蛋白症 / GM-CSF / 抗GM-CSF抗体 / 気管支肺胞洗浄液 / 抗GM-CSF自己抗体
Outline of Final Research Achievements

In this study, we approached therapeutic mechanisms of GM-CSF inhalation, a novel therapy for autoimmune pulmonary alveolar proteinosis. The studies on CT images of the patients, who underwent GM-CSF inhalation therapy, revealed that including intensity of the opacities to CT grading was useful for evaluating therapeutic response, suggesting improvement of intensity rather than extent of the opacities of more importance. Follow-up observation of the patients demonstrated that baseline %VC might be a prognostic factor for disease recurrence. Reduction of VC might be due to accumulation of surfactant-derived materials in the alveolar space, while fibrotic changes were not remarkable in the CT images of the patients. Notably, the CT grading also had significant correlation with serum markers such as SP-D and KL-6. Comparison of recombinant human GM-CSF derived from cells of three species revealed that sialylated oligosaccharide moieties prolong the bioactivity of rhGM-CSF in vitro.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (32 results)

All 2016 2015 2014 2013 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 5 results) Presentation (18 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Book (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Pulmonary alveolar proteinosis and granulocyte/macrophage-colony stimulating factor (GM-CSF) inhalation2016

    • Author(s)
      Tazawa R, Nakata K
    • Journal Title

      Espert Opinion on Orphan Drugs

      Volume: 4 Issue: 1 Pages: 115-123

    • DOI

      10.1517/21678707.2016.1123150

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Outcome of corticosteroid administration in autoimmune pulmonary alveolar proteinosis: a retrospective cohort study2015

    • Author(s)
      Keiichi Akasaka, Takahiro Tanaka, Nobutaka Kitamura, Shinya Ohkouchi, Ryushi Tazawa, Toshinori Takada, Toshio Ichiwata, Etsuro Yamaguchi, Masaki Hirose, Toru Arai, Kentaro Nakano, Takahito Nei, Haruyuki Ishii, Tomohiro Handa, Yoshikazu Inoue and Koh Nakata
    • Journal Title

      BMC Pulmonary Medicine

      Volume: 15 Issue: 1 Pages: 88-88

    • DOI

      10.1186/s12890-015-0085-0

    • NAID

      120005758416

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Possible Involvement of Lung Cells Harboring an Abnormal Karyotype in the Pathogenesis of Pulmonary Alveolar Proteinosis Associated with Myelodysplastic Syndrome.2015

    • Author(s)
      Moriyama M, Yano T, Furukawa T, Takada T, Ushiki T, Masuko M, Takizawa J, Sone H, Tazawa R, Saijo Y, Ishii H, Nakata K.
    • Journal Title

      Ann Am Thorac Soc.

      Volume: 12 Pages: 1251-1253

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A mathematical model to predict protein wash out kinetics during whole-lung lavage in autoimmune pulmonary alveolar proteinosis.2015

    • Author(s)
      Akasaka K, (12名略), Tazawa R, (7名略) Nakata K.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol

      Volume: 308 Issue: 2 Pages: 105-117

    • DOI

      10.1152/ajplung.00239.2014

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Up-regulation of cluster of differentiation (CD) 11b expression on the surface of canine granulocytes with human granulocyte-macrophage colony-stimulating factor (GM-CSF).2014

    • Author(s)
      Nakagaki K, Nunomura Y, Uchida K, Nakata K, Tazawa R.
    • Journal Title

      J Vet Med Sci.

      Volume: 76 Pages: 1173-1176

    • NAID

      130004432194

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low concentrations of recombinant granulocyte macrophage-colony stimulating factor derived from Chinese hamster ovary cells augments long-term bioactivity with delayed clearance in vitro2014

    • Author(s)
      Hashimoto A, Tanaka T, Itoh Y, Yamagata A, Kitamura N, Tazawa R, Nakagaki K, Nakata K.
    • Journal Title

      Cytokine

      Volume: 68 Issue: 2 Pages: 118-126

    • DOI

      10.1016/j.cyto.2014.03.009

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Duration of benefit in patients with autoimmune pulmonary alveolar proteinosis after inhaled granulocyte-macrophage colony-stimulating factor therapy.2014

    • Author(s)
      Tazawa R, Inoue Y, Arai T, Takada T, Kasahara Y, Hojo M, Ohkouchi S, Tsuchihashi Y, Yokoba M, Eda R, Nakayama H, Ishii H, Nei T, Morimoto K, Nasuhara Y, Ebina M, Akira M, Ichiwata T, Tatsumi K, Yamaguchi E, Nakata K.
    • Journal Title

      Chest

      Volume: 145 Issue: 4 Pages: 729-737

    • DOI

      10.1378/chest.13-0603

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Development of pulmonary alveolar proteinosis following exposure to dust after the Great East Japan Earthquake.2013

    • Author(s)
      Hisata S, Moriyama H, Tazawa R, Ohkouchi S, Ichinose M, Ebina M.
    • Journal Title

      Respir Investig

      Volume: 51 Issue: 4 Pages: 212-216

    • DOI

      10.1016/j.resinv.2013.04.005

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Light chain (κ/λ) ratio of GM-CSF autoantibodies is associated with disease severity in autoimmune pulmonary alveolar proteinosis.2013

    • Author(s)
      Nei T, Urano S, Itoh Y, Kitamura N, Hashimoto A, Tanaka T, Motoi N, Kaneko C, Tazawa R, Nakagaki K, Arai T, Inoue Y, Nakata K.
    • Journal Title

      Clin Immunol

      Volume: 149(3) Issue: 3 Pages: 357-364

    • DOI

      10.1016/j.clim.2013.10.002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] カニクイザルでのGM-CSF反復吸入投与と抗体産生2016

    • Author(s)
      田澤立之,中垣和英,伊藤祐子,橋本淳史,田中崇裕,赤坂圭一,中田 光
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-04-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 会長特別企画2 自己免疫性肺胞蛋白症:新たな治療戦略 GM-CSF吸入療法:前臨床試験2016

    • Author(s)
      田澤立之
    • Organizer
      第56回日本呼吸器学会学術講演会(招待講演)
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-04-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] GATA binding protein 2 (GATA2) mutation identified in a Japanese patient with adult-onset pulmonary alveolar proteinosis2016

    • Author(s)
      R. Tazawa, R. Sato, M. Ito, A. P. Hsu, Y. Ito, S. Akagawa, J. Tohyama, A. Hebisawa, K. Ohta, K. Nakata
    • Organizer
      13th International Congress of Human Genetics in 2016
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-04-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 70歳代で発症した顆粒球マクロファージコロニー刺激因子受容体α鎖変異による遺伝性肺胞蛋白症2015

    • Author(s)
      田澤立之,伊藤正行,中込一之,赤坂圭一,太田洋充,内田義孝,塩野文子,高田俊範,永田真,遠山潤,萩原弘一,金澤實,中田光
    • Organizer
      第60回日本人類遺伝学会
    • Place of Presentation
      京王プラザホテル(東京都・新宿区)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Inhalation of recombinant human granulocyte/macrophage-colony stimulating factor and induction of the GM-CSF antibody in pulmonary alveolar proteinosis2015

    • Author(s)
      R. Tazawa, K. Nakagaki, Y. Ito, A. Hashimoto, T. Tanaka, K. Akasaka, K. Nakata
    • Organizer
      American Thporacic Society International Conference 2015
    • Place of Presentation
      コロラドコンベンションセンター(米国コロラド州デンバー市)
    • Year and Date
      2015-05-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Analysis of alveolar macrophage form on BALF specimens in secondary pulmonary alveolar proteinosis2015

    • Author(s)
      H. Ishii, R. Tazawa, Y. Inoue, T. Saraya, T. Koide, T. Handa, M. Morita, S. Yamamoto, Y. Tanino, S. Ohkouchi, K. Tomii, K. Nakata
    • Organizer
      American Thporacic Society International Conference 2015
    • Place of Presentation
      コロラドコンベンションセンター(米国コロラド州デンバー市)
    • Year and Date
      2015-05-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GM-CSF autoantibody does not completely interfere thhe binding of GM-CSF to its receptor but blocks GM-CSF signaling strongly2015

    • Author(s)
      A. Hashimoto, T. Tanaka, M. Higuchi, Y. Itoh, K. Shiiya, K. Akasaka, R. Tazawa, K. Nakata
    • Organizer
      American Thporacic Society International Conference 2015
    • Place of Presentation
      コロラドコンベンションセンター(米国コロラド州デンバー市)
    • Year and Date
      2015-05-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sequential GM-CSF inhalation reinforces the efficiency of whole lung lavage to treat auto-immune pulmonary alveolar proteinosis2015

    • Author(s)
      S. Ohkouchi, K. Akasaka, T. Ichiwata, M. Ichinose, H. Kurosawa, K. Nakata, R. Tazawa
    • Organizer
      American Thporacic Society International Conference 2015
    • Place of Presentation
      コロラドコンベンションセンター(米国コロラド州デンバー市)
    • Year and Date
      2015-05-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Outcome of corticosteroids therapy in autoimmune pulmonary alveolar proteinosis2015

    • Author(s)
      K. Akasaka, T. Tanaka, K. Shiiya, A. Hashimoto, H. Ishii, S. Ohkouchi, R. Tazawa, N. Kitamura, T. Takada, K. Nakata
    • Organizer
      American Thporacic Society International Conference 2015
    • Place of Presentation
      コロラドコンベンションセンター(米国コロラド州デンバー市)
    • Year and Date
      2015-05-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel method for measuring low concentration of GM-CSF autoantibody in the sera of healthy subjects2015

    • Author(s)
      K. Shiiya, A. Hashimoto, T. Tanaka, K. Akasaka, Y. Itoh, R. Tazawa, K. Nakata
    • Organizer
      American Thporacic Society International Conference 2015
    • Place of Presentation
      コロラドコンベンションセンター(米国コロラド州デンバー市)
    • Year and Date
      2015-05-19
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] GM-CSF吸入薬の非臨床試験としての薬物動態解析方法の検討2015

    • Author(s)
      田澤立之,中垣和英,伊藤祐子,橋本淳史,田中崇裕,赤坂圭一,中田 光
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Rare Lung Diseases2014

    • Author(s)
      Tazawa R
    • Organizer
      19th Congress of Asian Pacific Society of Respirology
    • Place of Presentation
      Bali International Convention Centre, Nusa Dua, Bali, Indonesia
    • Year and Date
      2014-11-15
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] A Preclinical Study for Development of a New GM-CSF Inhalation Drug as a Treatment of Pulmonary Alveolar Proteinosis2014

    • Author(s)
      Tazawa R, Nakagaki K, Ito Y, Hashimoto A, Tanaka T, Akasaka K-I, Nakata K
    • Organizer
      19th Congress of Asian Pacific Society of Respirology
    • Place of Presentation
      Bali International Convention Centre, Nusa Dua, Bali, Indonesia
    • Year and Date
      2014-11-14
    • Related Report
      2014 Research-status Report
  • [Presentation] Adult-Onset Hereditary Pulmonary Alveolar Proteinosis Caused By CSF2RA Deletion2014

    • Author(s)
      R. Tazawa, K. Ito, T. Ogi, H. Ishii, T. Sakagami, Y. Ito, A. Hashimoto, T. Tanaka, K.-I. Akasaka, J. Tohyama, K. Nakata
    • Organizer
      Annual Meeting of American Thoracic Society 2014
    • Place of Presentation
      San Diego Convention Center, San Diego, CA, USA
    • Year and Date
      2014-05-18
    • Related Report
      2014 Research-status Report
  • [Presentation] 成人発症遺伝性肺胞蛋白症とGM-CSF受容体α鎖変異2014

    • Author(s)
      田澤立之,伊藤健一郎,荻喬博,石井晴之,(5名略)中田光
    • Organizer
      第54回日本呼吸器学会学術講演会
    • Place of Presentation
      大阪国際会議場,大阪市
    • Year and Date
      2014-04-25
    • Related Report
      2014 Research-status Report
  • [Presentation] GM-CSF 吸入製剤開発のための前臨床試験の検討2014

    • Author(s)
      田澤立之,中垣和英,伊藤祐子,橋本淳史,田中崇裕,赤坂圭一,中田光
    • Organizer
      第54回日本呼吸器学会学術講演会
    • Place of Presentation
      大阪国際会議場,大阪市
    • Year and Date
      2014-04-25
    • Related Report
      2014 Research-status Report
  • [Presentation] Vital Capacity And Recurrence After Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Inhalation Therapy For Pulmonary Alveolar Proteinosis.

    • Author(s)
      Tazawa R, (16名略),Nakata K.
    • Organizer
      American Thoracic society International conference 2013
    • Place of Presentation
      米国フィラデルフィア市
    • Related Report
      2013 Research-status Report
  • [Presentation] 肺胞蛋白症のGM-CSF吸入治療の予後と肺活量

    • Author(s)
      田澤立之, (15名略),中田光.
    • Organizer
      第53回日本呼吸器学会学術講演会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Book] EBM呼吸器疾患の治療2016

    • Author(s)
      田澤立之(分担執筆):肺胞蛋白症はどう治療するべきか,227-232頁,永井厚志監修,一ノ瀬正和 井上義一 舘田一博 弦間昭彦編集
    • Total Pages
      495
    • Publisher
      中外医学社 ,東京
    • Related Report
      2015 Annual Research Report
  • [Book] 今日の診断指針第7版2015

    • Author(s)
      田澤立之(分担執筆):肺胞蛋白症.1035-37頁 金澤一郎 永井良三総編集
    • Total Pages
      2013
    • Publisher
      医学書院,東京
    • Related Report
      2015 Annual Research Report
  • [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」,311-312頁2013

    • Author(s)
      田澤立之(分担執筆)
    • Total Pages
      1955
    • Publisher
      医学書院,東京
    • Related Report
      2013 Research-status Report
  • [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」,331-333頁2013

    • Author(s)
      田澤立之(分担執筆)
    • Total Pages
      513
    • Publisher
      南江堂,東京
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 酵母由来組換えヒトGM-CSFに特異的に結合するモノクローナル抗体2016

    • Inventor(s)
      中田 光,中垣 和英,田澤 立之
    • Industrial Property Rights Holder
      出願人 国立大学法人新潟大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-065437
    • Filing Date
      2016-03-29
    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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