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Establishment of new treatment strategies to prevent COPD exacerbation by improving airway mucosal defense fragility

Research Project

Project/Area Number 21K08148
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionTohoku University

Principal Investigator

Tamada Tsutomu  東北大学, 医学系研究科, 准教授 (80396473)

Co-Investigator(Kenkyū-buntansha) 村上 康司  東北大学, 大学病院, 助教 (70633725)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsCOPD増悪 / 気道粘膜防御能 / 脆弱性 / 粘液線毛輸送 / 末梢気道 / 粘膜防御能 / COPD / 気道分泌
Outline of Research at the Start

本研究は臨床的に対応が困難であったウイルス・細菌感染に伴うCOPD増悪の予防およびCOPDに対する吸入ステロイド投与後の気道感染の抑制を目的とする。申請者らの保有する独自の実験システムおよび協力者施設の網羅的解析システムを活用し、ヒトおよびヒト類似ブタ気道を対象として新鮮分泌液の質的特性やその抗菌活性、粘液線毛運動等への影響などを包括的に解析し、気道粘膜防御能の未知の脆弱性機序を解明する。気道分泌液の網羅的解析による新規物質の探索も並行して行うことで新たな治療標的分子および治療薬候補を同定しその効果を確認する。以上により、全てのCOPD増悪予防を実現する新規治療法開発の基礎を提供する。

Outline of Final Research Achievements

Prevention of exacerbations, which greatly influence the prognosis of COPD, is an urgent need for treatment strategies. In this study, we aimed to develop a new treatment method to improve the vulnerability of airway mucosal defense in COPD. We developed an airway fresh secretion visualization system and revealed that CFTR channel dysfunction causes pathological acidification of secretory pH. We reported these findings in the European Journal of Physiology. In order to further develop our research results, we are conducting functional analysis of peripheral airways using a fluorescence microscope system equipped with a high-resolution, high-speed camera. This research clarifies the relationship between decreased airway mucosal defense and mucociliary transport ability, making it possible to establish and early clinical application of a new safe and effective treatment method aimed at preventing all COPD exacerbations.

Academic Significance and Societal Importance of the Research Achievements

本邦ではCOPD患者500万人以上のうち治療を受けているのは20万人前後と少なく、年間死亡数も約16,000人前後で推移している。「健康日本21 第二次,三次」でも対策を講じるべき生活習慣病としてがん、循環器疾患、糖尿病と並びCOPDが取り上げられるなど社会的にも注目されており、予後に大きく影響するCOPD増悪抑制は治療戦略において急務である。ヒト同様の構造的および機能的特徴を有するブタ気道を用いた本研究により、気道粘膜防御能脆弱性と粘液線毛輸送能との関連を明らかにすることが可能で、将来全てのCOPD増悪予防を目的とした安全で有効な新規治療法の確立と早期臨床応用が可能となる。

Report

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

    (30 results)

All 2024 2023 2022 2021

All Journal Article (15 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 15 results,  Open Access: 15 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 13 results)

  • [Journal Article] CYP27A1-27-hydroxycholesterol axis in the respiratory system contributes to house dust mite-induced allergic airway inflammation2024

    • Author(s)
      Ito Tatsunori、Ichikawa Tomohiro、Yamada Mitsuhiro、Hashimoto Yuichiro、Fujino Naoya、Numakura Tadahisa、Sasaki Yusaku、Suzuki Ayumi、Takita Katsuya、Sano Hirohito、Kyogoku Yorihiko、Saito Takuya、Koarai Akira、Tamada Tsutomu、Sugiura Hisatoshi
    • Journal Title

      Allergology International

      Volume: 73 Issue: 1 Pages: 151-163

    • DOI

      10.1016/j.alit.2023.08.005

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations between birth weight and lung function in a Japanese adult population: The tohoku medical megabank community-based cohort study2023

    • Author(s)
      Ohe T, Yamada M, Hozawa A, Mitsune A, Fujino N, Ichikawa T, Koarai A, Tamada T, et al.
    • Journal Title

      Respiratory Investigation

      Volume: 61 Issue: 5 Pages: 588-600

    • DOI

      10.1016/j.resinv.2023.06.004

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Supersulphides provide airway protection in viral and chronic lung diseases2023

    • Author(s)
      Matsunaga Tetsuro、Sano Hirohito、Takita Katsuya、Morita Masanobu、Yamanaka Shun、Ichikawa Tomohiro、Numakura Tadahisa、Ida Tomoaki、Jung Minkyung、Ogata Seiryo、Yoon Sunghyeon、Fujino Naoya、Kyogoku Yorihiko、Akaike Takaaki、et al.
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 4476-4476

    • DOI

      10.1038/s41467-023-40182-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Novel Development of Sarcoidosis Following COVID-19 Vaccination and a Literature Review2022

    • Author(s)
      Numakura Tadahisa、Murakami Koji、Tamada Tsutomu、Yamaguchi Chiaki、Inoue Chihiro、Ohkouchi Shinya、Tode Naoki、Sano Hirohito、Aizawa Hiroyuki、Sato Kei、Mitsune Ayumi、Kurosawa Hajime、Nakazawa Toru、Sugiura Hisatoshi
    • Journal Title

      Internal Medicine

      Volume: 61 Issue: 20 Pages: 3101-3106

    • DOI

      10.2169/internalmedicine.0104-22

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2022-10-15
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical features of COVID-19 patients with rebound phenomenon after corticosteroid therapy2022

    • Author(s)
      Murakami Koji、Sano Hirohito、Tode Naoki、Tsukita Yoko、Sato Kei、Narita Daisuke、Kimura Nozomu、Matsumoto Shuichiro、Ono Yoshinao、Iwasaki Chikashi、Sugiyama Hatsumi、Suzuki Manami、Kakuto Sho、Konno Shuichi、Kanamori Hajime、Baba Hiroaki、Oshima Kengo、Takei Kentarou、Tokuda Koichi、Tamada Tsutomu、Sugiura Hisatoshi
    • Journal Title

      BMJ Open Respiratory Research

      Volume: 9 Issue: 1 Pages: e001332-e001332

    • DOI

      10.1136/bmjresp-2022-001332

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Subepicardial burn injuries in bullfrog heart induce electrocardiogram changes mimicking inferior wall myocardial infarction2022

    • Author(s)
      KAZAMA Itsuro、KUWANA Ryo、MUTO Mizuki、NAGANO Amu、FUJIMURA Ririka、ASADA Ayano、TAMADA Tsutomu、SHIMOYAMA Makoto
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 84 Issue: 9 Pages: 1205-1210

    • DOI

      10.1292/jvms.22-0243

    • ISSN
      0916-7250, 1347-7439
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pyridoxine Synergistically Potentiates Mast Cell-Stabilizing Property of Ascorbic Acid2022

    • Author(s)
      Kazama I, Sato Y, Tamada T
    • Journal Title

      Cellular Physiology and Biochemistry

      Volume: 56 Issue: 3 Pages: 282-292

    • DOI

      10.33594/000000534

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urine autotaxin levels reflect the disease activity of sarcoidosis2022

    • Author(s)
      Murakami Koji、Tamada Tsutomu、Saigusa Daisuke、Miyauchi Eisaku、Nara Masayuki、Ichinose Masakazu、Kurano Makoto、Yatomi Yutaka、Sugiura Hisatoshi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 4372-4372

    • DOI

      10.1038/s41598-022-08388-6

    • URL

      https://pure.teikyo.jp/en/publications/f82ba5f6-8784-4d36-8763-0baf43f2740c

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bicarbonate transport of airway surface epithelia in luminally perfused mice bronchioles2022

    • Author(s)
      Liu L, Yamamoto A, Yamaguchi M, Taniguchi I, Nomura N, Nakakuki M, Kozawa Y, Fukuyasu T, Higuchi M, Niwa E, Tamada T, Ishiguro H
    • Journal Title

      J Physiol Sci

      Volume: 72 Issue: 1 Pages: 1-16

    • DOI

      10.1186/s12576-022-00828-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Clinical Features of Patients with Sarcoidosis and Malignant Diseases in Japan2021

    • Author(s)
      Tamada T, Nara M, Murakami K, Gamo S, Aritake H, Shimizu M, Kazama I, Ichinose M and Sugiura H.
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 2 Pages: 209-216

    • DOI

      10.2169/internalmedicine.5441-20

    • NAID

      130007968940

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-01-15
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulation of leukocyte immunoglobulin-like receptor B4 on interstitial macrophages in COPD; their possible protective role against emphysema formation.2021

    • Author(s)
      Mitsune A, Yamada M, Fujino N, Numakura T, Ichikawa T, Suzuki A, Matsumoto S, Mitsuhashi Y, Itakura K, Makiguchi T, Koarai A, Tamada T, Endo S, Takai T, Okada Y, Suzuki S, Ichinose M, Sugiura H.
    • Journal Title

      Respir Res

      Volume: 22 Issue: 1 Pages: 232-232

    • DOI

      10.1186/s12931-021-01828-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of indacaterol on the LPS-evoked changes in fluid secretion rate and pH in swine tracheal membrane2021

    • Author(s)
      Aritake Hidemi、Tamada Tsutomu、Murakami Koji、Gamo Shunichi、Nara Masayuki、Kazama Itsuro、Ichinose Masakazu、Sugiura Hisatoshi
    • Journal Title

      Pflugers Archiv - European Journal of Physiology

      Volume: 473 Issue: 6 Pages: 883-896

    • DOI

      10.1007/s00424-021-02560-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Japanese respiratory society guidelines for the management of cough and sputum (digest edition).2021

    • Author(s)
      Mukae H et al.
    • Journal Title

      Respir Invest

      Volume: 59 Issue: 3 Pages: 270-290

    • DOI

      10.1016/j.resinv.2021.01.007

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Longitudinal Relationship Between Growth Differentiation Factor 11 and Physical Activity in Chronic Obstructive Pulmonary Disease2021

    • Author(s)
      Tanaka Rie、Koarai Akira、Yamada Mitsuhiro、Fujino Naoya、Ichikawa Tomohiro、Numakura Tadahisa、Onodera Katsuhiro、Kyogoku Yorihiko、Tamada Tsutomu、Miura Motohiko、Minakata Yoshiaki、Ichinose Masakazu、Sugiura Hisatoshi
    • Journal Title

      International Journal of Chronic Obstructive Pulmonary Disease

      Volume: Volume 16 Pages: 999-1006

    • DOI

      10.2147/copd.s301690

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PGC-1α regulates airway epithelial barrier dysfunction induced by house dust mite2021

    • Author(s)
      Saito Tsutomu、Ichikawa Tomohiro、Numakura Tadahisa、Yamada Mitsuhiro、Koarai Akira、Fujino Naoya、Murakami Koji、Yamanaka Shun、Sasaki Yusaku、Kyogoku Yorihiko、Itakura Koji、Sano Hirohito、Takita Katsuya、Tanaka Rie、Tamada Tsutomu、Ichinose Masakazu、Sugiura Hisatoshi
    • Journal Title

      Respiratory Research

      Volume: 22 Issue: 1 Pages: 63-63

    • DOI

      10.1186/s12931-021-01663-6

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] バイオ製剤の有用性 重症喘息の最適な気道管理~2型炎症、呼吸機能、気道分泌~2023

    • Author(s)
      玉田 勉
    • Organizer
      第32回 国際喘息学会日本・北アジア部会
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] COPD治療の最前線2023

    • Author(s)
      玉田 勉
    • Organizer
      第43回日本サルコイドーシス/肉芽腫性疾患学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] TSLP抑制が切り拓く重症喘息治療への新たなアプローチ2023

    • Author(s)
      玉田 勉
    • Organizer
      第117回日本呼吸器学会東北地方会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] TSLP抑制が切り拓く重症喘息治療への新たなアプローチ2023

    • Author(s)
      玉田 勉
    • Organizer
      第4回 日本喘息学会総会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ACO治療 up to date2023

    • Author(s)
      玉田 勉
    • Organizer
      第72回 日本アレルギー学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] トリプル製剤の使い方2023

    • Author(s)
      玉田 勉
    • Organizer
      第4回 日本喘息学会総会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Useful biomarkers for the diagnosis and treatment for asthma” Type 2 biomarkers for the diagnosis of asthma2022

    • Author(s)
      Tamada T
    • Organizer
      The 31st Congress of Interasma Japan/North Asia.
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 好酸球性重症喘息の病態と治療の実際 実臨床が結ぶ重症喘息治療の過去と未来2022

    • Author(s)
      玉田 勉
    • Organizer
      第71回日本アレルギー学会学術大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 第18回『千葉保之・本間日臣記念賞』受賞講演 多様な臓器病変とサルコイドーシスの病態に関する臨床的検討2022

    • Author(s)
      玉田 勉
    • Organizer
      第42回日本サルコイドーシス/肉芽腫性疾患学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Central & Direct から考えるIL-4/13 抑制の意義 ~Dupilumab が最適な患者像を考える~2022

    • Author(s)
      玉田 勉
    • Organizer
      第62回臨床呼吸機能講習会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 管理目標達成に向けて生物学的製剤に求められる役割とは?2022

    • Author(s)
      玉田 勉
    • Organizer
      第62回日本呼吸器学会学術講演会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Usefulness of plasma and urine lysophospholipids-producing enzymes as a prognostic marker for sarcoidosis.2021

    • Author(s)
      Murakami K, Tamada T, Saigusa D, Nara M, Miyauchi E, Kurano M, Yatomi Y, Sugiura H.
    • Organizer
      The 25th Congress of the Asian Pacific Society of Respirology (APSR 2021)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 重症喘息における管理目標達成に向けての治療選択2021

    • Author(s)
      玉田 勉
    • Organizer
      第246回日本呼吸器学会関東地方会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Type2炎症のバイオマーカー2021

    • Author(s)
      玉田 勉
    • Organizer
      第70回 日本アレルギー学会学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 重症喘息患者を対象としたバイオ製剤のベネフィットに関するインターネット調査 KOFU Study2021

    • Author(s)
      玉田 勉,福井謙哉,槇田直之,菅谷聡子,中島亮輔,有田嘉文,田代尚樹
    • Organizer
      第70回 日本アレルギー学会学術大会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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