Elucidating pathogenesis and developing novel biomarkers for idiopathic pulmonary fibrosis based on the ethnic difference

• Project/Area Number: 25860646
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Hiroshima University
• Principal Investigator: Ohshimo Shinichiro 広島大学, 大学病院, 講師 (50508132)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 間質性肺炎 / 特発性肺線維症 / 急性呼吸不全 / 急性増悪 / バイオマーカー / 人種差 / 予後 / 国際研究者交流 / ドイツ / 指定難病 / 生存率 / SNP

Outline of Final Research Achievements

Idiopathic pulmonary fibrosis, one of the Intractable Diseases in Japan, shows an acute deterioration and a resultant death in a short period, which has been named as acute exacerbation. We analyzed the Japanese and German patients with idiopathic pulmonary fibrosis, and demonstrated a significant ethnic difference in the incidence of acute exacerbation between the cohorts. The single nucleotide polymorphisms in TERT and Ang2 genes were associated with the incidence of acute exacerbation. In addition, GDF-15 protein was a novel biomarker for the diagnosis and predicting survival in idiopathic pulmonary fibrosis.

Research Products

• [Int'l Joint Research] Ruhrlandklinik, Duisburg-Essen Univ.(ドイツ)
• [Journal Article] Innovation in Analysis of Respiratory Sounds. (2016)
  • Author(s): Ohshimo S, Sadamori T, Tanigawa K.
  • Journal Title: Ann Intern Med Volume: 164 Issue: 9 Pages: 638-639
  • DOI: 10.7326/l15-0350
  • Peer Reviewed
• [Journal Article] MUC5B promoter polymorphism in Japanese patients with idiopathic pulmonary fibrosis. (2015)
  • Author(s): Horimasu Y, Ohshimo S, Bonella F, Tanaka S, Ishikawa N, Hattori N, Kohno N, Guzman J, Costabel U.
  • Journal Title: Respirology. Volume: 20 Issue: 3 Pages: 439-44
  • DOI: 10.1111/resp.12466
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A pilot study: a combined therapy using polymyxin-B hemoperfusion and extracorporeal membrane oxygenation for acute exacerbation of interstitial pneumonia. (2015)
  • Author(s): Itai J, Ohshimo S, Kida Y, Ota K, Iwasaki Y, Hirohashi N, Bonella F, Guzman J, Costabel U, Kohno N, Tanigawa K.
  • Journal Title: Sarcoidosis Vasc Diffuse Lung Dis Volume: 31 Pages: 343-349
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis (2014)
  • Author(s): Ohshimo S, Ishikawa N, Horimasu Y, Hattori N, Hirohashi N, Tanigawa K, Kohno N, Bonella F, Guzman J, Costabel U
  • Journal Title: Respir Med. Volume: 108 Issue: 7 Pages: 1031-9
  • DOI: 10.1016/j.rmed.2014.04.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differences in serum SP-D levels between German and Japanese subjects are associated with SFTPD gene polymorphisms. (2014)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, Tanaka S, Bonella F, Ohshimo S, Guzman J, Costabel U, Kohno N
  • Journal Title: BMC Med Genet Volume: 15 Issue: 1 Pages: 4-4
  • DOI: 10.1186/1471-2350-15-4
  • NAID: 120006799353
  • Peer Reviewed / Open Access
• [Journal Article] Baseline KL-6 Predicts Increased Risk for Acute Exacerbation of Idiopathic Pulmonary Fibrosis (2014)
  • Author(s): Shinichiro Ohshimo, Nobuhisa Ishikawa, Yasushi Horimasu, Noboru Hattori, Nobuyuki Hirohashi, Koichi Tanigawa, Nobuoki Kohno, Francesco Bonella, Josune Guzman, Ulrich Costabel
  • Journal Title: Respiratory Medicine Volume: in press
  • Peer Reviewed
• [Presentation] ECMO使用患者における予後因子としての赤血球分布幅 (2016)
  • Author(s): 大下慎一郎,木田佳子, 京 道人，島谷竜俊，鳥越勇佑，鈴木 慶，山賀聡之，岩崎泰昌，廣橋伸之，志馬伸朗
  • Organizer: 第43回日本集中治療医学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2016-02-11
• [Presentation] Comparative Analysis of Multiple Gene Polymorphisms for Acute Exacerbation of Idiopathic Pulmonary Fibrosis (2015)
  • Author(s): Shinichiro Ohshimo, Chihiro Yamaoka, Yasushi Horimasu, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori, Nobuyuki Hirohashi, Koichi Tanigawa, Francesco Bonella, Josune Guzman, Ulrich Costabel, Nobuoki Kohno
  • Organizer: European Respiratory Society (ERS) International Congress 2015
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 2015-09-26
  • Int'l Joint Research
• [Presentation] Benefit of veno-venous ECMO in patients with acute exacerbation of interstitial pneumonia (2015)
  • Author(s): Shinichiro Ohshimo, Yoshiko Kida, Kohei Ota, Kei Suzuki, Satoshi Yamaga, Yasumasa Iwasaki, Nobuyuki Hirohashi, Noboru Hattori, Nobuoki Kohno, Koichi Tanigawa
  • Organizer: Asia-Pacific ELSO 2015 - 2nd Conference of Asia-Pacific Chapter of Extracorporeal Life Support Organization
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-07-17
  • Int'l Joint Research
• [Presentation] Analysis of autopsy findings in patients with acute respiratory failure supported on V-V ECMO (2015)
  • Author(s): Yoshiko Kida, Shinichiro Ohshimo, Kohei Ota, Kei Suzuki, Satoshi Yamaga, Yasumasa Iwasaki, Nobuyuki Hirohashi, Koichi Tanigawa
  • Organizer: Asia-Pacific ELSO 2015 - 2nd Conference of Asia-Pacific Chapter of Extracorporeal Life Support Organization
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-07-17
  • Int'l Joint Research
• [Presentation] Successful use of V-VA ECMO in a patient with respiratory failure complicated by myocarditis (2015)
  • Author(s): Michihito Kyo, Shinichiro Ohshimo, Yoshiko Kida, Kohei Ota, Kei Suzuki, Satoshi Yamaga, Yasumasa Iwasaki, Nobuyuki Hirohashi, Koichi Tanigawa
  • Organizer: Asia-Pacific ELSO 2015 - 2nd Conference of Asia-Pacific Chapter of Extracorporeal Life Support Organization
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2015-07-17
  • Int'l Joint Research
• [Presentation] ARDSの疫学：患者の生命予後は改善されたのか？ (2015)
  • Author(s): 大下 慎一郎
  • Organizer: 第37回日本呼吸療法医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2015-07-17
  • Invited
• [Presentation] 日本人の間質性肺炎急性増悪症例における体外式膜型人工肺（ECMO）の有用性 (2015)
  • Author(s): 大下慎一郎，木田佳子，太田浩平，京 道人，島谷竜俊，儀賀普嗣，小山和宏，稲川嵩紘，鈴木 慶，山賀聡之，田邉優子，大谷直嗣，貞森拓磨，宇根一暢，津村 龍，岩崎泰昌，廣橋伸之，服部 登，河野修興，谷川攻一
  • Organizer: 第37回日本呼吸療法医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2015-07-17
• [Presentation] V-V ECMOを使用した成人急性呼吸不全症例における剖検診断の検討 (2015)
  • Author(s): 木田佳子, 大下慎一郎, 太田浩平, 山賀聡之, 鈴木慶, 田邉優子, 稲川嵩紘, 小山和宏, 儀賀普嗣, 京道人, 島谷竜俊, 宇根一暢, 大谷直嗣, 岩崎泰昌, 廣橋伸之, 河野修興, 谷川攻一
  • Organizer: 第37回日本呼吸療法医学会総会
  • Place of Presentation: 京都
  • Year and Date: 2015-07-17
• [Presentation] Growth Differentiation Factor-15 (GDF-15) as Prognostic Factor in German Patients with Idiopathic Pulmonary Fibrosis (2015)
  • Author(s): Shinichiro Ohshimo, Kosuke Hamai, Francesco Bonella, Chihiro Yamaoka, Yasushi Horimasu, Hiroshi Iwamoto, Nobuhisa Ishikawa, Kazunori Fujitaka, Hiroshi Murai, Hironobu Hamada, Noboru Hattori, Nobuyuki Hirohashi, Koichi Tanigawa, Josune Guzman, Ulrich Costabel, Nobuoki Kohno
  • Organizer: American Thoracic Society 2015 International Conference
  • Place of Presentation: Denver, CO, USA
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] Serum KL-6 Levels Correlate With Response To Pirfenidone In Idiopathic Pulmonary Fibrosis (2015)
  • Author(s): F. Bonella, S. Ohshimo, E. Boerner, J. Guzman, T. E. Wessendorf, U. Costabel
  • Organizer: American Thoracic Society 2015 International Conference
  • Place of Presentation: Denver, CO, USA
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] Growth Differentiation Factor-15 (GDF-15) as Prognostic Factor in Caucasians with Idiopathic Pulmonary Fibrosis (2015)
  • Author(s): Shinichiro Ohshimo, Kosuke Hamai, Francesco Bonella, Chihiro Yamaoka, Yasushi Horimasu, Hiroshi Iwamoto, Nobuhisa Ishikawa, Kazunori Fujitaka, Hiroshi Murai, Hironobu Hamada, Noboru Hattori, Nobuyuki Hirohashi, Koichi Tanigawa, Josune Guzman, Ulrich Costabel, Nobuoki Kohno
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-17
  • Int'l Joint Research
• [Presentation] HRCT Findings as a Predictive Factor for Acute Exacerbation of Idiopathic Pulmonary Fibrosis (2015)
  • Author(s): Chihiro Yamaoka, Yasushi Horimasu, Hiroshi Iwamoto, Shinichiro Ohshimo, Kazunori Fujitaka, Noboru Hattori, Hironobu Hamada, Nobuoki Kohno
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-17
  • Int'l Joint Research
• [Presentation] KL-6 changes in serum could predict the development of chronic lung allograft dysfunction in lung transplant recipients (2015)
  • Author(s): V. Besa, F. Bonella, S. Ohshimo, G. Weinreich, U.Costabel, M. Kamler, H. Teschler, U. Sommerwerck
  • Organizer: ISHLT 35th Annual Meeting and Scientific Sessions
  • Place of Presentation: Nice, France
  • Year and Date: 2015-04-15
  • Int'l Joint Research
• [Presentation] 間質性肺炎急性増悪における体外式膜型人工肺（ECMO）の有用性 (2015)
  • Author(s): 大下慎一郎，木田佳子，太田浩平，京 道人，島谷竜俊，儀賀普嗣，小山和宏，稲川嵩紘，鈴木 慶，山賀聡之，田邉優子，大谷直嗣，貞森拓磨，宇根一暢，津村 龍，岩崎泰昌，廣橋伸之，服部 登，河野修興，谷川攻一
  • Organizer: 日本医工学治療学会 第31回学術大会
  • Place of Presentation: 広島
  • Year and Date: 2015-03-27 – 2015-03-29
• [Presentation] 救急・集中治療領域における呼吸管理 (2015)
  • Author(s): 廣橋伸之 大下慎一郎 谷川攻一
  • Organizer: 日本医工学治療学会 第31回学術大会
  • Place of Presentation: 広島
  • Year and Date: 2015-03-27 – 2015-03-29
  • Invited
• [Presentation] ECMO有効活用へ向けた当院の取り組み (2015)
  • Author(s): 大下慎一郎
  • Organizer: 第42回 日本集中治療医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-09 – 2015-02-11
  • Invited
• [Presentation] 間質性肺炎急性増悪におけるECMOの有用性 (2015)
  • Author(s): 木田佳子，大下慎一郎，太田浩平，山賀聡史，鈴木慶、岩崎泰昌，廣橋伸之，谷川攻一
  • Organizer: 第42回 日本集中治療医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-09 – 2015-02-11
• [Presentation] 非HIV患者の重症ニューモシスチス肺炎に対する体外式膜型人工肺の有用性 (2015)
  • Author(s): 太田浩平，大下慎一郎，木田佳子，山賀聡之，鈴木慶，稲川嵩紘，宇根一暢，岩崎泰昌，廣橋伸之，谷川攻一
  • Organizer: 第42回 日本集中治療医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-09 – 2015-02-11
• [Presentation] アナフィラキシーにおける凝固異常の検討 (2015)
  • Author(s): 山賀聡之，大下慎一郎,木田佳子, 太田浩平，大谷直嗣，宇根一暢，岩崎泰昌，廣橋伸之，秀 道広，谷川攻一
  • Organizer: 第42回 日本集中治療医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-09 – 2015-02-11
• [Presentation] 敗血症診断におけるPresepsinの有用性の検討 (2015)
  • Author(s): 鈴木 慶, 大下 慎一郎, 京 道人, 小山 和宏, 田邊 優子, 稲川 嵩紘, 太田 浩平, 岩崎 泰昌, 廣橋 伸之, 谷川 攻一
  • Organizer: 第42回 日本集中治療医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-02-09 – 2015-02-11
• [Presentation] Prognostic indicators for patients with acute respiratory failure treated with high-frequency oscillatory ventilation (2015)
  • Author(s): Yuko Tanabe, Shinichiro Ohshimo, Yoshiko Kida, Kei Suzuki, Satoshi Yamaga, Kohei Ota, Kazunobu Une, Koichi Tanigawa
  • Organizer: 44th Critical Care Congress
  • Place of Presentation: Phoenix, Arizona, USA
  • Year and Date: 2015-01-17 – 2015-01-21
• [Presentation] Correlation of intracellular histamine and clinical symptoms in anaphylactic patients. (2015)
  • Author(s): Satoshi Yamaga, Satoshi Morioke, Shinichiro Ohshimo, Kei Suzuki, Yasumasa Iwasaki, Nobuyuki Hirohashi, Michihiro Hide, Koichi Tanigawa.
  • Organizer: 44th Critical Care Congress
  • Place of Presentation: Phoenix, Arizona, USA
  • Year and Date: 2015-01-17 – 2015-01-21
• [Presentation] GAP index as a predictor of acute exacerbation in idiopathic pulmonary fibrosis. (2014)
  • Author(s): Shinichiro Ohshimo, Yasushi Horimasu, Francesco Bonella, Chihiro Yamaoka, Hiroshi Iwamoto, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Hironobu Hamada, Noboru Hattori, Nobuyuki Hirohashi, Koichi Tanigawa, Josune Guzman, Ulrich Costabel, Nobuoki Kohno
  • Organizer: 3rd Combined WASOGBAL Meeting, 11th WASOG Meeting and 13th International Conference on BAL
  • Place of Presentation: Kusadasi, Turkey
  • Year and Date: 2014-10-08 – 2014-10-11
• [Presentation] Angiopoietin-2 Gene Polymorphism as Prognostic Factor in Caucasians with Idiopathic Pulmonary Fibrosis (2014)
  • Author(s): Shinichiro Ohshimo, Yasushi Horimasu, Francesco Bonella, Hiroshi Iwamoto, Nobuhisa Ishikawa, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Noboru Hattori, Nobuyuki Hirohashi, Koichi Tanigawa, Josune Guzman, Ulrich Costabel, Nobuoki Kohno
  • Organizer: European Respiratory Society International Congress 2014
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] Potential value of KL-6 in various interstitial lung diseases - New Aspects of the Clinical Value of Biomarkers in Diffuse Lung Diseases (2014)
  • Author(s): Shinichiro Ohshimo
  • Organizer: European Respiratory Society International Congress 2014
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-09-06 – 2014-09-10
  • Invited
• [Presentation] 高頻度振幅換気（HFOV）が有効なARDS患者をいかに選択するか - ARDS に対する換気様式の選択 (2014)
  • Author(s): 大下慎一郎，太田浩平，板井純治，山賀聡之，木田佳子，西田 翼，儀賀普嗣，小林靖孟，稲川嵩紘，大谷直嗣，宇根一暢，貞森拓磨，津村 龍，岩崎泰昌，廣橋伸之，河野修興，谷川攻一
  • Organizer: 第36回 日本呼吸療法医学会学術総会
  • Place of Presentation: 秋田
  • Year and Date: 2014-07-19 – 2014-07-20
  • Invited
• [Presentation] Impact of Ethnic Difference and TERT Gene Polymorphisms in the Acute Exacerbation of Idiopathic Pulmonary Fibrosis (2014)
  • Author(s): Shinichiro Ohshimo, Nobuhisa Ishikawa, Yasushi Horimasu, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Noboru Hattori, Francesco Bonella, Josune Guzman, Ulrich Costabel, Nobuoki Kohno
  • Organizer: American Thoracic Society 2014 International Conference
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2014-05-16 – 2014-05-21
• [Presentation] Impact of Ethnic Difference and TERT Gene Polymorphisms in the Acute Exacerbation of Idiopathic Pulmonary Fibrosis. (2014)
  • Author(s): Shinichiro Ohshimo, Nobuhisa Ishikawa, Yasushi Horimasu, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Noboru Hattori, Francesco Bonella, Josune Guzman, Ulrich Costabel, Nobuoki Kohno.
  • Organizer: The 54th Annual Meeting of The Japanese Respiratory Society
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] 人工呼吸管理の羅針盤～ゴールデンスタンダードを求めて～：新しいモニターシステム・画像・血清マーカー (2014)
  • Author(s): 大下慎一郎
  • Organizer: 第54回 日本呼吸器学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2014-04-25 – 2014-04-27
  • Invited
• [Presentation] 急性呼吸不全におけるWearable-ECMO開発への取組み (2014)
  • Author(s): 大下慎一郎，堀益 靖，太田浩平，岩本博志，石川暢久，髙橋秀暢，白石正夫，金指正言，都留稔了，Mattausch, Hans Juergen，三浦道子，谷川攻一，河野修興
  • Organizer: 第54回 日本呼吸器学会学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2014-04-25 – 2014-04-27
• [Presentation] Serum KL-6 levels is associated with long-term prognosis in lung transplant recipients (2014)
  • Author(s): Bessa V, Ohshimo S, Weinreich G , Bonella F, Costabel U, Kamler M, Teschler H, Sommerwerck U.
  • Organizer: International Society for Heart & Lung Transplantation 34th Annual Meeting
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2014-04-10 – 2014-04-13
• [Presentation] Ethnic difference and serum KL-6 as predictors for acute exacerbation of idiopathic pulmonary fibrosis (2013)
  • Author(s): Shinichiro Ohshimo, Nobuhisa Ishikawa, Yasushi Horimasu, Noboru Hattori, Nobuoki Kohno, Francesco Bonella, Josune Guzman, Ulrich Costabel
  • Organizer: 18th Annual Congress of Asian Pacific Society of Respirology
  • Place of Presentation: Yokohama
• [Presentation] Ethnic differences in the incidence of acute exacerbation in idiopathic pulmonary fibrosis (2013)
  • Author(s): Shinichiro Ohshimo, Nobuhisa Ishikawa, Yasushi Horimasu, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Noboru Hattori, Francesco Bonella, Nobuoki Kohno, Josune Guzman, Ulrich Costabel
  • Organizer: American Thoracic Society International Conference 2013
  • Place of Presentation: Philadelphia, USA