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2018 Fiscal Year Annual Research Report

Multifaceted approach to the pathogenesis and novel treatments for acute exacerbation of idiopathic pulmonary fibrosis based on the ethnic difference and neutrophilic transcription factor

Research Project

Project/Area Number 16K09541
Research InstitutionHiroshima University

Principal Investigator

大下 慎一郎  広島大学, 医歯薬保健学研究科(医), 准教授 (50508132)

Co-Investigator(Kenkyū-buntansha) 志馬 伸朗  広島大学, 医歯薬保健学研究科(医), 教授 (00260795)
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords国際研究者交流 / ドイツ / 急性呼吸不全 / 指定難病 / 予後 / 生存率
Outline of Annual Research Achievements

<平成30年度>
①間質性肺炎急性増悪の発症危険因子として,口腔内細菌叢による潜在感染症の関与について解析を継続した.特発性肺線維症140名(日本70名・ドイツ70名),健常者260名(日本100名・ドイツ160名),および細菌性肺炎30名のコホートを使用して,口腔内常在菌16種類の抗体価を解析した.その結果,急性増悪発症率に対して促進的に作用する細菌と防御的に作用する細菌があることが分かった.
②C57BL/6マウスにブレオマイシンを投与し間質性肺炎動物モデルを作成した.気管支肺胞洗浄液中・肺組織中における,好中球転写因子C/EBPの発現解析(real time PCR)・ELISAを行った.しかし,いずれの検討においても,C/EBP familyの発現は,健常マウスと比較して有意差を認めなかった.
<研究期間全体(平成28~30年度)>
①ドイツと複数回の連携を取り,日本・ドイツの間質性肺炎患者コホートのデータを追跡調査し,予後・急性増悪発症率をアップデートした.日本人の急性増悪発症率はドイツ人比べ有意に高率であることが確認された(15% vs 8%).
②日本人・ドイツ人IPF患者血清を用いて,Helicobacter pylori・口腔内細菌叢16種の抗体価を評価した.その結果,血清H. pylori抗体価2.3 U/mL以上は,IPF急性増悪の危険因子であることが分かった.口腔内細菌叢では,抗体価が高値であるとIPF急性増悪の発症率が高くなる細菌(Porphyromonas, Tannerella, Campylobacter)と, 逆にIPF急性増悪の発症率が低くなる細菌(Aggregatibacter, Prevotella, Fusobcterium)があることが明らかになった.TannerellaとAggregatibacterの比が高値である患者は,有意に高率に急性増悪を発症することが明らかになった.

  • Research Products

    (16 results)

All 2019 2018 Other

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

  • [Int'l Joint Research] Duisburg-Essen University(ドイツ)

    • Country Name
      GERMANY
    • Counterpart Institution
      Duisburg-Essen University
  • [Journal Article] Potential confounders for the effect of high-flow nasal cannula oxygen therapy2019

    • Author(s)
      Yamaga S, Ohshimo S, Shime N.
    • Journal Title

      Crit Care

      Volume: 23 Pages: 17

    • DOI

      10.1186/s13054-019-2310-3

    • Peer Reviewed / Open Access
  • [Journal Article] Changes in serum KL-6 levels are associated with the development of chronic lung allograft dysfunction in lung transplant recipients2019

    • Author(s)
      Bessa V, Bonella F, Ohshimo S, Weinreich G, Kleibrink B, Costabel U, Aigner C, Kamler M, Taube C, Sommerwerck U
    • Journal Title

      Transpl Immunol

      Volume: 52 Pages: 40-44

    • DOI

      10.1016/j.trim.2018.10.006

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The western Japan chaotic rainstorm disaster: a brief report from Hiroshima.2018

    • Author(s)
      Ohshimo S, Sadamori T, Shime N
    • Journal Title

      J Intensive Care

      Volume: 6 Pages: 82

    • DOI

      10.1186/s40560-018-0354-0

    • Peer Reviewed / Open Access
  • [Journal Article] Serial measurements of KL-6 for monitoring activity and recurrence of interstitial pneumonia with anti-aminoacyl-tRNA synthetase antibody: A retrospective cohort study2018

    • Author(s)
      Yamaguchi K, Iwamoto H, Sakamoto S, Horimasu Y, Masuda T, Miyamoto S, Nakashima T, Ohshimo S, Fujitaka K, Hamada H, Kohno N, Hattori N
    • Journal Title

      Medicine (Baltimore).

      Volume: 97 Pages: e13542

    • DOI

      10.1097/MD.0000000000013542

    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of extracorporeal membrane oxygenation outcome for influenza-associated acute respiratory failure in Japan between 2009 and 20162018

    • Author(s)
      Ohshimo S, Shime N, Nakagawa S, Nishida O, Takeda S; Committee of the Japan ECMO project.
    • Journal Title

      J Intensive Care

      Volume: 6 Pages: 38

    • DOI

      10.1186/s40560-018-0306-8

    • Peer Reviewed / Open Access
  • [Presentation] Imbalance in the oral bacterial flora as a risk factor for acute exacerbation in idiopathic pulmonary fibrosis2019

    • Author(s)
      Shinichiro Ohshimo, Hiromi Nishi, Koji Hosokawa, Yasushi Horimasu, Shintaro Miyamoto, Hiroshi Iwamoto, Hironobu Hamada, Hiroyuki Kawaguch, Francesco Bonella, Josune Guzman, Ulrich Costabel, Noboru Hattori, Nobuaki Shime
    • Organizer
      European Respiratory Society International Congress 2019
    • Int'l Joint Research
  • [Presentation] Clinical utility of CCL15 as a prognostic biomarker for hypersensitivity pneumonitis2019

    • Author(s)
      M. Watanabe, Y. Horimasu, H. Iwamoto, K. Yamaguchi, S. Sakamoto, T. Masuda, T. Nakashima, S. Miyamoto, S. Ohshimo, K. Fujitaka , H. Hamada, N. Kohno, N. Hattori
    • Organizer
      European Respiratory Society International Congress 2019
    • Int'l Joint Research
  • [Presentation] Fine crackles quantitative value can help the diagnosis of interstitial lung diseases - Clinical utility of the innovative analyzing system of respiratory sounds2019

    • Author(s)
      Yasushi Horimasu, Shinichiro Ohshimo, Kakuhiro Yamaguchi, Shinjiro Sakamoto, Takeshi Masuda, Taku Nakashima, Shintaro Miyamoto, Hiroshi Iwamoto, Takuma Sadamori, Kazunori Fujitaka, Hironobu Hamada, Nobuaki Shime, Noboru Hattori
    • Organizer
      European Respiratory Society International Congress 2019
    • Int'l Joint Research
  • [Presentation] Modified GAP stage as a predictor of acute exacerbation in idiopathic pulmonary fibrosis2018

    • Author(s)
      Shinichiro Ohshimo, Yoshiko Kida, Michihito Kyo, Koji Hosokawa, Yasushi Horimasu, Shintaro Miyamoto, Hiroshi Iwamoto, Hironobu Hamada, Noboru Hattori, Francesco Bonella, Josune Guzman, Ulrich Costabel, Nobuaki Shime
    • Organizer
      European Respiratory Society International Congress 2018
    • Int'l Joint Research
  • [Presentation] Extent of the honeycombing area and the presence of traction bronchiectasis are risk factors for a poor prognosis in patients with pleuroparenchymal fibroelastosis2018

    • Author(s)
      Masashi Namba, Takeshi Masuda, Kakuhiro Yamaguchi, Shinjiro Sakamoto, Yasushi Horimasu, Taku Nakashima, Shintarou Miyamoto, Hiroshi Iwamoto, Shinichiro Ohshimo, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori
    • Organizer
      European Respiratory Society International Congress 2018
    • Int'l Joint Research
  • [Book] ICU実践ハンドブック改訂版 - 病態ごとの治療・管理の進め方2019

    • Author(s)
      清水敬樹・編,大下慎一郎,他・著
    • Total Pages
      719
    • Publisher
      羊土社
    • ISBN
      978-4758118453
  • [Book] 呼吸器ジャーナル 特集・非侵襲的呼吸管理の実践講座 - 酸素療法からハイフロー,NIVまで症例で学ぶ2019

    • Author(s)
      富井啓介・編,大下慎一郎,他・著
    • Total Pages
      174
    • Publisher
      医学書院
    • ISBN
      978-4260028943
  • [Book] ER・ICU 100のピットフォール2019

    • Author(s)
      志馬伸朗・編,大下慎一郎,他・著
    • Total Pages
      290
    • Publisher
      中外医学社
    • ISBN
      9784498166042
  • [Book] 集中治療,ここだけの話2018

    • Author(s)
      田中竜馬・編,大下慎一郎,他・著
    • Total Pages
      448
    • Publisher
      医学書院
    • ISBN
      9784260036719
  • [Book] THE LUNG Perspectives 特集テーマ「急性期の呼吸器管理を検証する」2018

    • Author(s)
      大下慎一郎,他・著
    • Total Pages
      104
    • Publisher
      メディカルレビュー社
    • ISBN
      9784779221415

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Published: 2019-12-27  

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