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Disease activity in autoimmune pulmonary alveolar proteinosis

Research Project

Project/Area Number 16K09530
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

Akasaka Keiichi  新潟大学, 医学部, 非常勤講師 (50364542)

Co-Investigator(Kenkyū-buntansha) 高田 俊範  新潟大学, 医歯学総合病院, 特任教授 (40361919)
田澤 立之  新潟大学, 医歯学総合病院, 准教授 (70301041)
中田 光  新潟大学, 医歯学総合病院, 教授 (80207802)
谷野 功典  福島県立医科大学, 医学部, 准教授 (10443863)
福島 康次  獨協医科大学, 医学部, 教授 (00254996)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肺胞蛋白症 / 病勢 / サイトカイン / 自己免疫性肺胞蛋白症 / サイトカインプロファイル / 自己免疫性 / サイトカインパネル / 病勢マーカー / 全肺洗浄 / 臨床呼吸器学
Outline of Final Research Achievements

We evaluated comprehensive serum cytokine/chemokine levels of 66 samples that were obtained from 22 cases of autoimmune alveolar proteinosis. As an intractable severe case showed each condition of progression and remission, cytokine/chemokine levels were measured six times among three years, we confirmed elevated levels of INF-γ, IL-1 α, and IP-10 at the remission phase. These elevated inflammatory cytokines are concerning to macrophage differentiation towards M1 macrophage. According to these analyzations, we hypothesized that differentiation to M1 macrophage could induce remission. Therefore, of 21 other cases, we measured serum cytokine/chemokine panel and collected clinical conditions. However, we could not detect any correlation with cytokine/chemokine levels and disease severity.

Academic Significance and Societal Importance of the Research Achievements

自己免疫性肺胞蛋白症においてサイトカインレベルと病勢の関係ははっきりとせず、何らかのサイトカインもしくはM1/M2マクロファージの分化が病勢に影響を及ぼしている可能性は低い。今まで肺胞蛋白症の病勢に関する研究は幾つかあるが、いずれも病勢マーカーをみつけられていない。このため、病勢に関与する因子は複合的である可能性が高い。現在、GM-CSF吸入療法が有効であることが分かり保険収載に向けて動いているが、この薬での効果はそれほど高いものではない。一方で、なんらかの他のサイトカイン製剤を加えてやれば効果がでそうという簡単な理論はなさそうである。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (24 results)

All 2020 2019 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (18 results) (of which Int'l Joint Research: 7 results) Book (1 results)

  • [Journal Article] Autoimmune pulmonary alveolar proteinosis developed during immunosuppressive treatment in polymyositis with interstitial lung disease: a case report2020

    • Author(s)
      Sato S.、Akasaka K.、Ohta H.、Tsukahara Y.、Kida G.、Tsumiyama E.、Kusano K.、Oba T.、Nishizawa T.、Kawabe R.、Yamakawa H.、Amano M.、Matsushima H.、Takada T.
    • Journal Title

      BMC Pulmonary Medicine

      Volume: 20 Issue: 1

    • DOI

      10.1186/s12890-020-1110-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modified eosinophil adhesion in pulmonary alveolar proteinosis caused by <i>CSF2RA</i> deletion2019

    • Author(s)
      Uchida Y, Nakagome K, Tazawa R, Akasaka K, Ito M, Haga Y, Komiyama KI, Soma T, Nakata K, Nagata M.
    • Journal Title

      Allergology International

      Volume: 68 Issue: Supplement.1 Pages: S14-S16

    • DOI

      10.1016/j.alit.2019.05.015

    • NAID

      130007709733

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peripheral alveolar nitric oxide concentration reflects alveolar inflammation in autoimmune pulmonary alveolar proteinosis.2018

    • Author(s)
      Hirano T, Ohkouchi S, Tode N, Kobayashi M, Ono M, Satoh T, Mitsuishi Y, Watanabe A, Tabata M, Irokawa T, Ogawa H, Sugiura H, Kikuchi T, Akasaka K, Tazawa R, Inoue Y, Nakata K, Kurosawa H, Ichinose M.
    • Journal Title

      ERJ open research

      Volume: 4 Issue: 1 Pages: 00071-2017

    • DOI

      10.1183/23120541.00071-2017

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sequential Granulocyte-Macrophage Colony-Stimulating Factor Inhalation after Whole-Lung Lavage for Pulmonary Alveolar Proteinosis. A Report of Five Intractable Cases.2017

    • Author(s)
      Ohkouchi S, Akasaka K, Ichiwata T, Hisata S, Iijima H, Takada T, Tsukada H, Nakayama H, Machiya J, Irokawa T, Ogawa H, Shibata Y, Ichinose M, Ebina M, Nukiwa T, Kurosawa H, Nakata K, Tazawa R.
    • Journal Title

      Ann Am Thorac Soc.

      Volume: 8 Pages: 1298-1304

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elderly-onset hereditary pulmonary alveolar proteinosis and its cytokine profile.2017

    • Author(s)
      Ito M, Nakagome K, Ohta H, Akasaka K, Uchida Y, Hashimoto A, Shiono A, Takada T, Nagata M, Tohyama J, Hagiwara K, Kanazawa M, Nakata K, Tazawa R.
    • Journal Title

      BMC Pulmonary Medicine.

      Volume: 印刷中 Issue: 1 Pages: 40-40

    • DOI

      10.1186/s12890-017-0382-x

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 当院で経験した自己免疫性肺胞蛋白症9例における画像所見の検討2019

    • Author(s)
      赤坂圭一、太田啓貴、森田喜久子、木田言、塚原雄太、積山慧美里、西沢知剛 大場智広、川辺梨恵、山川英晃、佐藤新太郎、天野雅子、松島秀和.
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GM-CSF受容体α鎖変異による成人発症遺伝性肺胞蛋白症における好酸球接着能2019

    • Author(s)
      内田義孝、中込一之、田澤立之、赤坂圭一、芳賀佳之、小宮山謙一郎、杣知行、中田光、永田真
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アスペルギローマを合併したNSIPパターンの線維化性自己免疫性肺胞蛋白症の1剖検例2019

    • Author(s)
      赤坂圭一、吉澤政俊、太田啓貴、木田言、塚原雄太、積山慧美里、草野賢次 西沢知剛、大場智広、川辺梨恵、山川英晃、佐藤新太郎、天野雅子、安達章子 松島秀和
    • Organizer
      第236回日本呼吸器学会関東地方会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 当院で経験した自己免疫性肺胞蛋白症9例における画像所見の検討2019

    • Author(s)
      赤坂圭一, 太田啓貴, 森田喜久子, 木田言, 塚原雄太, 積山慧美里, 西沢知剛, 大場智広, 川辺梨恵, 山川英晃, 佐藤新太郎, 天野雅子, 松島秀和
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] GM-CSF受容体α鎖変異による成人発症遺伝性肺胞蛋白症における好酸球接着能.2019

    • Author(s)
      内田義孝、中込一之、田澤立之、赤坂圭一、芳賀佳之、小宮山謙一郎、杣知行、中田光、永田真.
    • Organizer
      第59回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] Disease Activity in Autoimmune Pulmonary Alveolar Proteinosis Analyzed by a Multiplex Immunoassay System.2018

    • Author(s)
      Keiichi Akasaka , Tmotaka Nishizawa , Tomohiro Oba , Kazumasa Ohashi, Rie Kawabe, Hideaki Yamakawa, Shintaro Satoh, Masako Amano, Hidekazu Matsushima, Toshinori Takada
    • Organizer
      23th Congress of the Asian Pacific Society of Respirology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Keiichi Akasaka, Yuta Tsukahara, Tomotaka Nishizawa, Tomohiro Oba, Masako Amano, Hidekazu Matsushima2018

    • Author(s)
      A Case of Exogenous Lipoid Pneumonia Caused by Sesame Oil Pulling Successfully Treated with Whole Lung Lavage.
    • Organizer
      American Thoracic Society 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 全肺洗浄術が著効したごま油うがいによる外因性リポイド肺炎の1例.2018

    • Author(s)
      赤坂圭一、塚原雄太、栗岩早希 、西沢知剛 、大場智広 、川辺梨恵 、佐藤新太郎、天野雅子、松島秀和.
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 全肺洗浄術が著効したごま油うがいによる外因性リポイド肺炎の1例.2018

    • Author(s)
      4.赤坂 圭一, 塚原 雄太, 木田 言, 江本 かおり,積山 彗美里,栗岩 早希, 西沢 知剛, 大場 智広, 川辺 梨恵, 佐藤 新太郎, 天野 雅子, 松島 秀和
    • Organizer
      第164回日本呼吸器内視鏡学会関東支部会,東京,2018.3
    • Related Report
      2017 Research-status Report
  • [Presentation] Disease Activity in Autoimmune Pulmonary Alveolar Proteinosis Analyzed by a Multiplex Immunoassay System.2017

    • Author(s)
      1.Keiichi Akasaka , Kazumasa Ohashi , Tmotaka Nishizawa , Tomohiro Oba , Rie Kawabe , Shintaro Satoh , Masako Amano , Kazuhide Matsushima , Toshinori Takada
    • Organizer
      American Thoracic Society, May 20 2017, Washington D.C, USA.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Change in Distribution of Pulmonary Blood During Whole Lung Lavage in Patients with Autoimmune Pulmonary Alveolar Proteinosis: A Simulation-Based Study.2017

    • Author(s)
      2.Hitoshi Tsuyuzaki , Kanji Uchida , Yuho Tamai , Keiichi Akasaka , Toshio Ichiwata , Koh Nakata , Yoshikazu Inoue , Yoshitsugu Yamada
    • Organizer
      American Thoracic Society, May 20 2017, Washington D.C, USA.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Chronic Inhalation of Recombinant Human Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) and GM-CSF Antibody in Nonhuman Primates.2017

    • Author(s)
      3.Ryushi Tazawa , Kazuhide Nakagaki , Yuko Ito , Mariko Iizuka , Atsushi Hashimoto , Ryu Nakano , Takahiro Tanaka , Keiichi Akasaka , Shiho Takeuchi , Koh Nakata
    • Organizer
      American Thoracic Society, May 20 2017, Washington D.C, USA.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 全肺洗浄術での体位の違いによる低酸素血症の程度に関する検討.2017

    • Author(s)
      1.赤坂 圭一, 内田 寛治, 福田 のぞみ, 栗岩 早希, 西沢 知剛, 大場 智広, 川辺 梨恵, 佐藤 新太郎, 天野 雅子, 松島 秀和
    • Organizer
      第56回日本呼吸器学会学術講演会.東京,2017, 4
    • Related Report
      2017 Research-status Report
  • [Presentation] 顆粒球マクロファージコロニー刺激因子(GM-CSF)慢性吸入動物での抗体中和能の推移.2017

    • Author(s)
      2.田澤 立之, 中垣 和英, 伊藤 祐子, 橋本 淳史, 中野 龍, 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.東京,2017, 4
    • Related Report
      2017 Research-status Report
  • [Presentation] Elderly-Onset Hereditary Pulmonary Alveolar Proteinosis and CSF2RA Mutation2016

    • Author(s)
      26.Ryushi Tazawa, Masayuki Ito, Kazuyuki Nakagome, Keiichi Akasaka, Hiromitsu Ohta, Yoshitaka Uchida, Ayako Shiono, Toshinori Takada, Makoto Nagata, Jun Tohyama, Koichi Hagiwara, Minoru Kanazawa, Koh Nakata
    • Organizer
      American Thoracic Society
    • Place of Presentation
      San Francisco, USA.
    • Year and Date
      2016-05-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Light Chain Genotype Analysis of GM-CSF Autoantibody in Autoimmune Pulmonary Alveolar Proteinosis by Next Generation Sequencing2016

    • Author(s)
      27.Atsushi Hashimoto, Takahiro Tanaka, Astushi Hayakawa, Yuko Itoh, Takahito Nei, Keiko Shiiya, Maiko Higuchi, Kazuhide Nakagaki, Toshinori Takada, Keiichi Akasaka, Ryushi Tazawa, Koh Nakata
    • Organizer
      American Thoracic Society,
    • Place of Presentation
      San Francisco, USA.
    • Year and Date
      2016-05-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 片側肺の全肺洗浄術で対側肺の改善を認めた肺胞蛋白症の検討2016

    • Author(s)
      60.赤坂 圭一, 石山 貴章, 大橋 和政, 鈴木 和夫, 日比 美智子, 中込 一之, 高田 俊範
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      京都国際会館(京都府京都市)
    • Year and Date
      2016-04-20
    • Related Report
      2016 Research-status Report
  • [Presentation] びまん性肺疾患の基礎 カニクイザルでのGM-CSF吸入薬の反復吸入投与と抗体産生2016

    • Author(s)
      61.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
      京都国際会館(京都府京都市)
    • Year and Date
      2016-04-20
    • Related Report
      2016 Research-status Report
  • [Book] 気管支肺胞洗浄【BAL】法の手引き 改訂第3版2017

    • Author(s)
      日本呼吸器学会びまん性肺疾患学術部会/厚生労働省難治性疾患政策研究事業びまん性肺疾患に関する調査研究班
    • Total Pages
      9
    • Publisher
      克誠堂出版
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2021-02-19  

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