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Development of predictive markers of drug response for precision medicine in COPD patients

Research Project

Project/Area Number 19K16450
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionUniversity of Shizuoka

Principal Investigator

Hirai Keita  静岡県立大学, 薬学部, 講師 (30740203)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords慢性閉塞性肺疾患 / 喘息 / バイオマーカー / マイクロRNA / 治療有効性 / 遺伝子発現解析 / ステロイド抵抗性
Outline of Research at the Start

本研究は静岡県立総合病院を研究協力施設とする、前向き観察研究である。各倫理委員会の承認は既に得ており、2018年3月より対象患者の登録・検体の収集を開始しており、臨床研究①の患者登録・検体採取は2019年3月の終了を予定している。臨床研究②の患者登録・検体採取は2020年9月の終了を予定しており、2019年度は80%以上の患者登録を目指す。全ての測定を2021年9月までに終了し、統計解析を2021年12月までに終了する予定である。

Outline of Final Research Achievements

There remains a need to develop specific markers to identify COPD patients who are treatable with drugs for asthma. These indices could contribute to improving the prognosis of COPD patients. In this study, we identified specific plasma microRNAs that can distinguish patients with features of both COPD and asthma. Moreover, we found biomarkers for the responsiveness of anti-IL-5 receptor blockers (benralizumab).

Academic Significance and Societal Importance of the Research Achievements

COPD患者は世界における死亡原因の第3位に位置し、我が国においても死亡者数の減少傾向は認められていない。本研究により見出された、COPDと喘息の両方の特徴を併せ持つ患者を鑑別することが可能なバイオマーカーを用いることで、喘息治療薬が有効なCOPD患者を臨床において特定することが可能になるものと考えられる。これにより、COPD患者の予後改善、死亡者数の減少に将来的に貢献できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 1 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results) Remarks (6 results)

  • [Journal Article] Benralizumab restores gene and microRNA expression involved in steroid sensitivity in severe asthma2021

    • Author(s)
      Hirai Keita、Uehara Sekiko、Shirai Toshihiro、Rachi Yuuka、Kimura Tomoki、Akamatsu Taisuke、Itoh Kunihiko
    • Journal Title

      Allergy

      Volume: 76 Issue: 8 Pages: 2589-2592

    • DOI

      10.1111/all.14819

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Circulating microRNA‐15b‐5p as a biomarker for asthma‐COPD overlap2020

    • Author(s)
      Hirai Keita、Shirai Toshihiro、Shimoshikiryo Takayuki、Ueda Megumi、Gon Yasuhiro、Maruoka Shuichiro、Itoh Kunihiko
    • Journal Title

      Allergy

      Volume: 76 Issue: 3 Pages: 766-774

    • DOI

      10.1111/all.14520

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oscillometry improves earlier than spirometry after benralizumab initiation in severe asthma2020

    • Author(s)
      Shirai Toshihiro、Akamatsu Taisuke、Hirai Keita、Watanabe Hirofumi、Tamura Kanami、Kishimoto Yutaro、Saigusa Mika
    • Journal Title

      Allergy

      Volume: - Issue: 10 Pages: 2678-2680

    • DOI

      10.1111/all.14339

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Annual changes in forced oscillation technique parameters correlate with FEV1 decline in patients with asthma, COPD, and asthma-COPD overlap2020

    • Author(s)
      Tanaka Yuko、Hirai Keita、Nakayasu Hiromasa、Tamura Kanami、Masuda Toshihiro、Takahashi Shingo、Watanabe Hirofumi、Kishimoto Yutaro、Ohishi Kyouhei、Saigusa Mika、Akamatsu Taisuke、Yamamoto Akito、Morita Satoru、Asada Kazuhiro、Shirai Toshihiro
    • Journal Title

      Allergology International

      Volume: 69 Issue: 4 Pages: 626-627

    • DOI

      10.1016/j.alit.2020.03.013

    • NAID

      130007926265

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of the Association between Circulating Vitamin D<sub>3</sub> Levels and Clinical Outcomes in Patients with Asthma and Chronic Obstructive Pulmonary Disease: A Prospective Observational Study2019

    • Author(s)
      Hirai Keita、Shirai Toshihiro、Suzuki Yuya、Shimomura Tatsuki、Itoh Kunihiko
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 11 Pages: 1861-1866

    • DOI

      10.1248/bpb.b19-00385

    • NAID

      130007740609

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-11-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of Gene Expression Associated with Glucocorticoid-Induced Transcript 1 (GLCCI1) on Severe Asthma and Future Exacerbation2019

    • Author(s)
      Hirai Keita、Shirai Toshihiro、Rachi Yuuka、Uehara Sekiko、Ueda Megumi、Nakatani Eiji、Itoh Kunihiko
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 10 Pages: 1746-1752

    • DOI

      10.1248/bpb.b19-00476

    • NAID

      130007722397

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-10-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of Stratified and Personalized Medicine Based on Pharmacogenomic and Pharmacokinetic Analyses2019

    • Author(s)
      Hirai Keita
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 139 Issue: 10 Pages: 1253-1258

    • DOI

      10.1248/yakushi.19-00145

    • NAID

      130007721896

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2019-10-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Forced oscillation technique may identify severe asthma2019

    • Author(s)
      Shirai Toshihiro、Hirai Keita、Gon Yasuhiro、Maruoka Shuichiro、Mizumura Kenji、Hikichi Mari、Itoh Kunihiko、Hashimoto Shu
    • Journal Title

      The Journal of Allergy and Clinical Immunology: In Practice

      Volume: 7 Issue: 8 Pages: 2857-2860.e1

    • DOI

      10.1016/j.jaip.2019.05.036

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] BIOMARKERS FOR PREDICTING FUTURE EXACERBATIONS IN ADULT PATIENTS WITH ASTHMA2019

    • Author(s)
      平井 啓太、白井 敏博、伊藤 邦彦
    • Journal Title

      Japanese Journal of Allergology

      Volume: 68 Issue: 8 Pages: 942-947

    • DOI

      10.15036/arerugi.68.942

    • NAID

      130007709339

    • ISSN
      0021-4884, 1347-7935
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 喘息およびCOPD患者の治療層別化マーカーの構築研究2022

    • Author(s)
      平井 啓太
    • Organizer
      第62回日本呼吸器学会学術講演会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Treatable traitsとは? 閉塞性肺疾患患者の治療層別化に向けたバイオマーカー構築の重要性2022

    • Author(s)
      平井 啓太
    • Organizer
      第38回日本TDM学会・学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] High serum EDN levels may be a predictive biomarker for the responsiveness of benralizumab treatment2021

    • Author(s)
      Uehara S, Hirai K, Shirai T, Akamatsu T, Itoh K.
    • Organizer
      25th Annual Congress of the Asian Pacific Society of Respirology (APSR 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 好酸球性気道炎症の病態から考える生物学的製剤の選択2021

    • Author(s)
      白井 敏博, 平井 啓太
    • Organizer
      第70回日本アレルギー学会学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 薬物療法の層別化・個別化に向けたバイオマーカー構築の重要性2021

    • Author(s)
      平井 啓太
    • Organizer
      第37回日本TDM学会・学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 薬剤師による研究~薬物治療に貢献する強力な一手~2021

    • Author(s)
      平井 啓太
    • Organizer
      医療薬学フォーラム2021
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] プレシジョンメディスンの実現を目指した治療層別化マーカーの構築2021

    • Author(s)
      平井 啓太
    • Organizer
      日本薬学会第142年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 重症喘息患者におけるステロイド抵抗性関連分子に対する生物学的製剤の影響2021

    • Author(s)
      平井 啓太
    • Organizer
      第3回日本アレルギー学会 東海地方会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 重症喘息患者におけるステロイド感受性関連分子に対するベンラリズマブの影響2021

    • Author(s)
      平井 啓太、上原 星輝子、白井 敏博、良知 優花、木村朋起、赤松 泰介、伊藤 邦彦
    • Organizer
      第61回日本呼吸器学会学術講演会
    • Related Report
      2020 Research-status Report
  • [Presentation] Benralizumab restored expression of key molecules involved in steroid-resistance in patients with severe asthma2020

    • Author(s)
      Keita Hirai, Toshihiro Shirai, Taisuke Akamatsu, Sekiko Uehara, Yuka Rachi, Kanami Tamura, Yutaro Kishimoto, Mika Saigusa, Kazuhiro Asada, Kunihiko Itoh
    • Organizer
      European Respiratory Society (ERS) International Congress
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Annual change in forced oscillation technique correlates with FEV1 decline in patients with asthma, COPD, and asthma-COPD overlap2020

    • Author(s)
      Yuko Tanaka, Keita Hirai, Hiromasa Nakayasu, Kanami Tamura, Toshihiro Masuda, Shingo Takahashi, Hirofumi Watanabe, Yutaro Kishimoto, Kyohei Oishi, Mika Saigusa, Taisuke Akamatsu, Akito Yamamoto, Satoru Morita, Kazuhiro Asada, Toshihiro Shirai
    • Organizer
      American Academy of Allergy, Asthma & Immunology Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effectiveness of benralizumab in patients with severe asthma2020

    • Author(s)
      Hirofumi Watanabe, Taisuke Akamatsu, Keita Hirai, Hiromasa Nakayasu, Kanami Tamura, Toshihiro Masuda, Shingo Takahashi, Yuko Tanaka, Yutaro Kishimoto, Kyohei Oishi, Mika Saigusa, Akito Yamamoto, Satoru Morita, Kazuhiro Asada, Toshihiro Shirai
    • Organizer
      American Academy of Allergy, Asthma & Immunology Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] NLRP3インフラマソーム遺伝子多型と喘息の病態との関連2019

    • Author(s)
      鈴木裕也、平井啓太、良知優花、白井敏博、伊藤邦彦
    • Organizer
      日本薬学会東海支部総会・大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Asthma-COPD Overlapの診断における血清ペリオスチン, YKL-40測定の意義2019

    • Author(s)
      12.平井啓太、白井敏博、權 寧博、丸岡秀一郎、水村賢司、引地麻梨、Cecile Holweg、伊藤邦彦、井上博雅、橋本 修
    • Organizer
      第49回吸入療法研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 喘息およびCOPDのプレシジョンメディスンの実現を目指した病態解析研究2019

    • Author(s)
      平井啓太
    • Organizer
      第13回次世代を担う若手医療薬科学シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/hiraik

    • Related Report
      2021 Annual Research Report
  • [Remarks] ORCiD

    • URL

      https://orcid.org/0000-0001-8027-3508

    • Related Report
      2021 Annual Research Report
  • [Remarks] publons

    • URL

      https://publons.com/researcher/K-6290-2014/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 信州大学 研究者総覧

    • URL

      https://soar-rd.shinshu-u.ac.jp/profile/ja.jFfCuhkV.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] ORCID

    • URL

      https://orcid.org/0000-0001-8027-3508

    • Related Report
      2019 Research-status Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/hiraik/

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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