Biomakers associated with ventilator associated lung injury

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390460
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: HASHIMOTO Satoru Kyoto Prefectural University of Medicine, 医学研究科, 准教授 (90167578)
• Co-Investigator(Kenkyū-buntansha): SHIME Nobuaki 京都府立医科大学, 医学研究科, 講師 (00260795) ; AMAYA Fumimasa 京都府立医科大学, 医学研究科, 講師 (60347466) ; UENO Hiroshi 京都府立医科大学, 医学研究科, 助教 (20381965) ; ISHIZAKA Akitoshi 慶応義塾大学, 医学部, 教授 (90176181) ; HASEGAWA Naoki 慶応義塾大学, 医学部, 講師 (20198724)
• Project Period (FY): 2008 – 2010
• Keywords: 人工呼吸関連肺損傷 / ラミニン5γ2断片 / 細胞外ATP / neutral endopeptidase(NEP)活性 / モエシン

Research Abstract

We studied several biomarkers that could predict the mortality or efficacy of therapy in patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS). For this aim, we conducted clinical and basic studies. In clinical studies, we sampled blood and alveolar epithelial lining fluid which was facilitated by the method of bronchoalveolar microsampling in ALI/ARDS patients. As a result, we found significantly higher amount of amino-terminal fragment of laminin gamma2-chain in blood and in epithelial lining fluids of patients with ALI/ARDS. And also, neutral endopeptidase (NEP) activity in ALI/ARDS patients were significantly lower compared to control group. In basic studies we conducted the experiments in similar lung injurious settings. In addition, extracellular ATP and moesin expression in association with lung injury were studied using mouse model. These studies confirmed our hypothesis that these biomarkers increase or decrease in accordance with the severity of the disease. Thus these biomarkers should be examined in a larger clinical trial whether it could useful for the physicians.

Research Products

• [Journal Article] Laminin γ2 fragments are increased in the circulation of patients with early-phase acute lung injury. (2010)
  • Author(s): Katayama M, Ishizaka A, Kotani K, Ware L, Matthay M, Hashimoto S.
  • Journal Title: Intensive Care Med 36(3) Pages: 476-486
  • Peer Reviewed
• [Journal Article] Expression of neutral endopeptidase activity during clinical and experimental acute lung injury. (2010)
  • Author(s): Hashimoto S, Amaya F, Oh-Hashi K, Kiuchi, K, Hashimoto S.
  • Journal Title: Respir Res 11 Pages: 164
  • Peer Reviewed
• [Journal Article] Concentrations of clarithromycin and active metabolite in the epithelial lining fluid of patients with mycobacterium avium complex pulmonary disease. (2009)
  • Author(s): Hasegawa N, Nishimura T, Watabnabe M, Tasaka S, Nakano Y, Yamazaki K, Hashimoto S, Nishimura M, Ishizaka A.
  • Journal Title: Pulmonary pharmacology & therapeutics 22(3) Pages: 190-193
  • Peer Reviewed
• [Journal Article] Neutrophil elastase activity in acute respiratory distress syndrome. (2008)
  • Author(s): Hashimoto S, Okayama Y, Shime N, Kimura A, Funakoshi Y, Kawabata K, Ishizaka A, Amaya F
  • Journal Title: Respirology 13(4) Pages: 581-584
  • Peer Reviewed
• [Journal Article] Dysregulation of lung injury and repair in moesin-deficient mice treated with intratracheal bleomycin. (2008)
  • Author(s): Hashimoto S, Amaya F, Matsuyama H, Ueno H, Kikuchi S, Tanaka M, Watanabe Ebina M, Ishizaka A, Tsukita S, Hashimoto S
  • Journal Title: Am J Physiol 295(5) Pages: L566-L574
  • Peer Reviewed
• [Journal Article] Acute lung inflammation and ventilator-induced lung injury caused by ATP via the P2Y receptors : an experimental study. (2008)
  • Author(s): Matsuyama H, Amaya F, Hashimoto S, Ueno H, Beppu S, Mizuta M, Shime N, Ishizaka A, Hashimoto S
  • Journal Title: Respiratory Research. 9 Pages: 79
  • Peer Reviewed