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elucidation of the mechanism of lung fibrosis with hypersensitivity pneumonitis

Research Project

Project/Area Number 21K20895
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0902:General internal medicine and related fields
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Furusawa Haruhiko  東京医科歯科大学, 大学院医歯学総合研究科, 講師 (40632154)

Project Period (FY) 2021-08-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords過敏性肺炎 / 遺伝子解析 / 遺伝子発現解析 / 気管支肺胞洗浄 / 線維化 / MUC5B / DSP
Outline of Research at the Start

過敏性肺炎(Hypersensitive Pneumonitis: HP)は抗原の反復吸入および感作によって生じるびまん性肺疾患である。線維性HPは特発性肺線維症(Idiopathic pulmonary fibrosis; IPF)と類似する予後不良な疾患であり、有効な治療は確立されていない。MUC5BやDSPなどさまざまな遺伝子多型が疾患感受性遺伝子として同定されており、HPの病態にこれら遺伝子がどのように関わっているかを解明するため本研究を計画した。

Outline of Final Research Achievements

Hypersensitive Pneumonitis (HP) is a diffuse lung disease caused by the repeated inhalation and sensitization of antigens. A subset of HP patients, who experience continuous antigen exposure, develop fibrotic HP. This study aims to identify the risk genes associated with HP and elucidate how these genes contribute to the clinical manifestations of the disease. In non-Hispanic white HP patients, the genes TERC, DSP, MUC5B, and IVD were found to be associated with fibrosis. Subsequently, a genome-wide association study (GWAS) was conducted on Japanese HP patients, comparing their data with that of healthy controls. We are currently investigating the susceptibility genes for the disease.

Academic Significance and Societal Importance of the Research Achievements

HP は抗原の反復吸入および感作によって生じるびまん性肺疾患であり、線維性HPは特発性肺線維症(idiopathic pulmonary fibrosis; IPF)と類似した病態と経過を辿る予後不良な疾患であり、IPFとの鑑別が問題となる。一方で原因抗原に持続曝露された人の中でHP発症に至るのは 4~20%程度であり、また発症したHPのなかで線維化が進展する症例は1/2~1/3程度であるため、原因抗原の同定や予後予測は困難である。発症や予後を規定する遺伝子を同定することで、IPFとの鑑別や早期治療介入、また重症化を予測して肺移植や抗線維化薬の導入などを早期に行うことができると考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (13 results)

All 2024 2023 2022 2021

All Journal Article (9 results) (of which Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (4 results)

  • [Journal Article] Assessment of clinical relevance of antigen improves diagnostic accuracy of hypersensitivity pneumonitis2024

    • Author(s)
      Iijima Yuki、Ejima Masaru、Yamana Takashi、Sonoda Shiro、Shibata Sho、Shirai Tsuyoshi、Okamoto Tsukasa、Furusawa Haruhiko、Tateishi Tomoya、Adachi Takuya、Mori Mio、Kirimura Susumu、Anzai Tatsuhiko、Takahashi Kunihiko、Miyazaki Yasunari
    • Journal Title

      BMC Pulmonary Medicine

      Volume: 24 Issue: 1 Pages: 1-8

    • DOI

      10.1186/s12890-024-02849-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants2023

    • Author(s)
      Peljto Anna L.、Blumhagen Rachel Z.、Walts Avram D.et al.
    • Journal Title

      American Journal of Respiratory and Critical Care Medicine

      Volume: 207 Issue: 9 Pages: 1194-1202

    • DOI

      10.1164/rccm.202207-1331oc

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Deep convolutional neural network for differentiating between sarcoidosis and lymphoma based on [18F]FDG maximum-intensity projection images2023

    • Author(s)
      Aoki Hikaru、Miyazaki Yasunari、Anzai Tatsuhiko、Yokoyama Kota、Tsuchiya Junichi、Shirai Tsuyoshi、Shibata Sho、Sakakibara Rie、Mitsumura Takahiro、Honda Takayuki、Furusawa Haruhiko、Okamoto Tsukasa、Tateishi Tomoya、Tamaoka Meiyo、Yamamoto Masahide、Takahashi Kunihiko、Tateishi Ukihide、Yamaguchi Tetsuo
    • Journal Title

      European Radiology

      Volume: 34 Issue: 1 Pages: 374-383

    • DOI

      10.1007/s00330-023-09937-x

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of vasculitis in a case with severe asthma treated with benralizumab and low-dose corticosteroid2023

    • Author(s)
      Umezawa Natsuka、Sasaki Hirokazu、Furusawa Haruhiko、Kawata Daisuke、Hata Chiina、Yasuda Shinsuke
    • Journal Title

      Allergology International

      Volume: 72 Issue: 1 Pages: 179-181

    • DOI

      10.1016/j.alit.2022.08.004

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Journal Article] Understanding the process of people with hypersensitivity pneumonitis implementing continuous antigen avoidance and their affecting situations: A grounded theory study2022

    • Author(s)
      Kawamoto Yuko、Yatomi Yumiko、Furusawa Haruhiko、Hanzawa Satoshi、Miyazaki Yasunari、Tanaka Makoto
    • Journal Title

      Journal of Clinical Nursing

      Volume: 32 Issue: 11-12 Pages: 2880-2891

    • DOI

      10.1111/jocn.16395

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful diagnosis of humidifier lung by individual provocation test to a responsible environment, a case report2022

    • Author(s)
      Murakami T、Iijima Y、Ando T、Ejima M、Shirai Tsuyoshi、Furusawa H、Okamoto T、Tateishi T、Tamaoka M、Miyazaki Y
    • Journal Title

      Respiratory Medicine Case Reports

      Volume: 37 Pages: 101639-101639

    • DOI

      10.1016/j.rmcr.2022.101639

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A phase II feasibility study of carboplatin and nab‐paclitaxel for advanced non‐small cell lung cancer patients with interstitial lung disease YLOG01142022

    • Author(s)
      Sakashita Hi、Uchibori K、Jin Y、Tsutsui T、Honda T、Sakakibara R、Mitsumura T、Nukui Y、Shirai Tsuyoshi、Masuo M、Suhara K、Furusawa H、Yamashita T、Ohba T、Saito K、Takagiwa J、Miyashita Y、Inase N、Miyazaki Y
    • Journal Title

      Thoracic Cancer

      Volume: 0 Issue: 9 Pages: 1-9

    • DOI

      10.1111/1759-7714.14376

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Common idiopathic pulmonary fibrosis risk variants are associated with hypersensitivity pneumonitis2022

    • Author(s)
      Furusawa Haruhiko、Peljto Anna L、Walts Avram D、Cardwell Jonathan、Molyneaux Philip L、 Lee Joyce S、Fernandez Perez Evans R、Wolters Paul J、Yang Ivana V、Schwartz David A
    • Journal Title

      Thorax

      Volume: 77 Issue: 5 Pages: 508-510

    • DOI

      10.1136/thoraxjnl-2021-217693

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 慢性過敏性肺炎の遺伝子発現解析2021

    • Author(s)
      古澤 春彦, 宮崎 泰成
    • Journal Title

      呼吸器内科

      Volume: 40 Pages: 182-189

    • NAID

      40022670064

    • Related Report
      2021 Research-status Report
  • [Presentation] 当院で診断した加湿器肺の臨床像と治療後の臨床経過に関する後方視的検討2022

    • Author(s)
      惠島 将, 山田 貴之, 飯島 裕基, 白井 剛, 岡本 師, 立石 知也, 古澤 春彦, 宮崎 泰成
    • Organizer
      日本アレルギー学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] サルコイドーシス患者の疲労感.2021

    • Author(s)
      古澤 春彦, 齋藤 弘明, 山下 将平, 石塚 聖洋, 岡本 師, 立石 知也, 宮崎 泰成.
    • Organizer
      日本サルコイドーシス/肉芽腫性疾患学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 間質性肺炎での気管支肺胞洗浄液中コラーゲン分解産物の測定.2021

    • Author(s)
      田坂 有理, 古澤 春彦, 多賀 祐喜, 宮崎 泰成.
    • Organizer
      日本アレルギー学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 当院におけるクライオバイオプシー導入後のMDD(他職種合議)診断の状況.2021

    • Author(s)
      熊谷 隆, 飯島 裕基, 白井 剛, 島田 翔, 山名 高志, 榊原 里江, 三ツ村 隆弘, 柴田 翔, 本多 隆行, 古澤 春彦, 立石 知也, 岡本 師, 玉岡 明洋, 桐村 進, 明石 巧, 足立 拓也, 斎田 幸久, 宮崎 泰成.
    • Organizer
      日本呼吸器内視鏡学会
    • Related Report
      2021 Research-status Report

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Published: 2021-10-22   Modified: 2025-01-30  

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