Approach to inflammatory lung diseases by improving paracellular enviroment

• Project/Area Number: 26462767
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Keio University
• Principal Investigator: FUJISHIMA SEITARO 慶應義塾大学, 医学部(信濃町), 准教授 (00173419)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症性肺疾患 / ARDS / 高濃度酸素 / 急性呼吸促迫症候群 / 酸素中毒 / PAMPs / DAMPs

Outline of Final Research Achievements

1) We exposed human vascular endothelial cells to hyperoxia, and found the induction of interleukin-8 gene expression. This response was exacerbated under the co-incubation with tumor necrosis factor alpha or lipopolysaccharide, suggesting the exaggerated toxicity of hyperoxia in patients under critical condition. We further found the involvement of intracellular pattern-recognition receptors in this mechanism. ２) We found that differentiation of human embryonic stem cells into lung epithelial cells was facilitated by an air-liquid interface method. ３) We previously found the exaggerated bleomycin-induced acute lung injury in interleukin-17 deficient mice. By the current analysis, involvement of pathways not including dendritic cells or interleukin-12 were suggested. ４) We comprehensively analyzed lung cytokines in patients with acute respiratory distress syndrome, and found the involvement of interleukin-1beta, interferon-gamma, and interleukin-17.

Research Products

• [Journal Article] Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 (2017)
  • Author(s): Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, et al.
  • Journal Title: Crit Care Med Volume: 45 Issue: 3 Pages: 486-552
  • DOI: 10.1097/ccm.0000000000002255
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Infection site is predictive of outcome in acute lung injury associated with severe sepsis and septic shock. (2016)
  • Author(s): 3.Fujishima S, Gando S, Daizoh S, Kushimoto S, Ogura H, Mayumi T, Takuma K, Kotani J, Yamashita N, Tsuruta R, Takeyama N, Shiraishi S, Araki T, Suzuki K, Ikeda H, Miki Y, Suzuki Y, Yamaguchi Y, Aikawa N.
  • Journal Title: Respirology Volume: 21 Issue: 5 Pages: 898-904
  • DOI: 10.1111/resp.12769
  • Peer Reviewed / Open Access
• [Journal Article] Plasma cathepsin S and cathepsin S/cystatin C ratios are potential biomarkers for COPD (2016)
  • Author(s): Nakajima T, Nakamura H, Caroline A. Owen CA, Yoshida S, Tsuduki K, Chubachi S, Shirahata T, Mashimo S, Nakamura M, Takahashi S, Minematsu N, Tateno H, Fujishima S, Asano K, Celli BR, Betsuyaku T
  • Journal Title: Disease Markers Volume: 2016:4093870 Pages: 1-9
  • DOI: 10.1155/2016/4093870
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Organ dysfunction as a new standard for defining sepsis (2016)
  • Author(s): Fujishima S
  • Journal Title: Inflamm Regen Volume: 36 Issue: 1
  • DOI: 10.1186/s41232-016-0029-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 日本版敗血症診療ガイドライン2016 目次・要約・基本理念と概要 (2016)
  • Author(s): 西田修、小倉裕司、井上茂亮、射場敏明、今泉均、江木盛時、垣花泰之、久志本成樹、小谷穣治、貞広智仁、志馬伸朗、中川聡、中田孝明、布宮伸、林淑朗、藤島清太郎、升田好樹、松嶋麻子、松田直之、織田成人、田中裕、日本版敗血症診療ガイドライン2016 作成特別委員会
  • Journal Title: Journal of the Japanese Society of Intensive Care Medicine Volume: 24 Issue: Supplement2 Pages: n/a
  • DOI: 10.3918/jsicm.24S0001
  • NAID: 130005397978
  • ISSN: 1340-7988, 1882-966X
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic factors of Streptococcus pneumoniae sepsis in adults. (2016)
  • Author(s): Hifumi T, Fujishima S, Abe T, Kiriu N, Inoue J, Kato H, Koido Y, Kawakita K, Kuroda Y, Sasaki J, Hori S.
  • Journal Title: The American Journal of Emergency Medicine Volume: 34 Issue: 2 Pages: 202-206
  • DOI: 10.1016/j.ajem.2015.10.025
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct effects of endogenous interleukin-23 on eosinophilic airway inflammation in response to different antigens (2015)
  • Author(s): Ogawa R, Suzuki Y, Kagawa S, Masaki K, Fukunaga K, Yoshimura A, Fujishima S, Terashima T, Betsuyaku T, Asano K
  • Journal Title: Allergology International Volume: 64 Issue: Supplement.1 Pages: 24-29
  • DOI: 10.1016/j.alit.2015.04.005
  • NAID: 130005099477
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Impact of serum glucose levels on disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis (2015)
  • Author(s): Kushimoto S, Gando S, Saitoh D, Mayumi T, Ogura H, Fujishima S, Araki T, Ikeda H, Kotani J, Miki Y, Shiraishi S, Suzuki K, Suzuki Y, Takeyama N, Takuma K, Tsuruta R, Yamaguchi Y, Yamashita N, Aikawa N
  • Journal Title: Acute Medicine & Surgery Volume: 2 Issue: 1 Pages: 21-28
  • DOI: 10.1002/ams2.59
  • Peer Reviewed / Open Access
• [Journal Article] 急性呼吸促迫症候群（ARDS）の病態生理 (2015)
  • Author(s): 藤島清太郎
  • Journal Title: 呼吸器内科 Volume: 28 Pages: 87-91
• [Journal Article] A multicenter, prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines (2014)
  • Author(s): Fujishima S, Gando S, et al
  • Journal Title: J Infect Chemother Volume: 20(2) Issue: 2 Pages: 115-120
  • DOI: 10.1016/j.jiac.2013.09.003
  • Peer Reviewed / Open Access
• [Journal Article] Plasma cytokine profiles related to smoking-sensitivity and phenotypes of chronic obstructive pulmonary disease (2014)
  • Author(s): Nakamura M, Nakamura H, Minematsu N, Chubachi S, Miyazaki M, Yoshida S, Tsuduki K, Shirahata T, Mashimo S, Takahashi S, Nakajima T, Tateno H, Fujishima S, Betsuyaku T
  • Journal Title: Biomarkers Volume: 19 Issue: 5 Pages: 368-77
  • DOI: 10.3109/1354750x.2014.915342
  • Peer Reviewed
• [Journal Article] Pathophysiology and biomarkers of acute respiratory distress syndrome (2014)
  • Author(s): Fujishima S
  • Journal Title: J Intensive Care Volume: 2 Issue: 1 Pages: 32-32
  • DOI: 10.1186/2052-0492-2-32
  • Peer Reviewed / Open Access
• [Journal Article] ALI/ARDSの診断と治療：バイオマーカー (2014)
  • Author(s): 藤島清太郎
  • Journal Title: 呼吸器内科 Volume: 25 Pages: 204-11
• [Journal Article] 急性呼吸促迫症候群：画像とバイオマーカーからの病態評価 (2014)
  • Author(s): 藤島清太郎
  • Journal Title: 日本呼吸ケア・リハビリテーション学会誌 Volume: 24 Pages: 220-7
  • NAID: 130005109124
• [Presentation] 敗血症性ARDS (2017)
  • Author(s): 藤島清太郎
  • Organizer: 第44回日本集中治療医学会学術集会
  • Place of Presentation: さっぽろ芸文館（北海道札幌市）
  • Invited
• [Presentation] 成人敗血症患者に対する副腎皮質ステロイド投与について (2016)
  • Author(s): 藤島清太郎、今泉均、升田好樹、巽博臣、藤村直幸、井上茂亮、射場敏明、垣花泰之、久志本成樹、小谷穣治、貞弘智仁、志馬伸朗、中川聡、中田孝明、布宮伸、林淑朗、松田直之、松嶋麻子、江木盛時、小倉裕司、西田修、織田成人、田中裕
  • Organizer: 第44回日本救急医学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Invited
• [Presentation] ALI/ARDSに対する多施設共同前向き観察研究 (2015)
  • Author(s): 藤島清太郎
  • Organizer: 第43回日本救急医学会総会・学術集会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2015-10-22
  • Invited
• [Presentation] 敗血症性ARDSに対する治療戦略 (2015)
  • Author(s): 藤島清太郎
  • Organizer: 第26回日本急性血液浄化学会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-10-09
  • Invited
• [Presentation] ALI/ARDS患者肺局所サイトカインの網羅的解析による病態評価の試み (2015)
  • Author(s): 中野泰、藤島清太郎、宮庄拓、田坂定智、橋本悟、長谷川直樹、別役智子
  • 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
  • Invited
• [Presentation] 急性呼吸促迫症候群：ガイドライン後の知見と最近の話題 (2015)
  • Author(s): 藤島清太郎
  • Organizer: 第12回日本集中治療医学会主催リフレッシャーセミナー
  • Place of Presentation: 東京
  • Year and Date: 2015-02-08
  • Invited
• [Presentation] 敗血症バンドル遵守率と死亡率による診療の質の評価 (2014)
  • Author(s): 藤島清太郎
  • Organizer: 第27回日本外科感染症学会総会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-12-05
  • Invited
• [Presentation] 救急診療の場で遭遇する感染症の特徴 (2014)
  • Author(s): 藤島清太郎
  • Organizer: 第42回日本救急医学会総会・学術集会／第193回ICD講習会
  • Place of Presentation: 福岡
  • Year and Date: 2014-10-30
  • Invited
• [Presentation] ARDS：ガイドライン後の知見と最近のトピックス (2014)
  • Author(s): 藤島清太郎
  • Organizer: 第42回日本救急医学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2014-10-29
  • Invited
• [Book] 呼吸器疾患診療最新ガイドライン： 肺水腫 (2014)
  • Author(s): 藤島清太郎
  • Total Pages: 395
  • Publisher: 最新医学社