Does the prognosis of ventilator-associated pneumonia (VAP) affected by innate immune response in the lung?

• Project/Area Number: 26860778
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Department of Clinical Research, National Hospital Organization Nagasaki Medical Center
• Principal Investigator: Yamamoto Kazuko 独立行政法人国立病院機構(長崎医療センター臨床研究センター), 臨床研究センター, 客員研究員 (10398167)
• Research Collaborator: MIZGERD Joseph P. Boston University School of Medicine, Pulmonary Center, Director ; OTA Kenji 長崎大学, 大学院 医歯薬学総合研究科病態解析・診断学, 大学院生 ; YAMASAKI Kazumi 独立行政法人 長崎医療センター, 臨床研究センター, 臨床疫学研究室長
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 人工呼吸器関連肺炎 / 予後因子 / サイトカイン / 肺上皮 / ARDS / 自然免疫 / 肺上皮細胞 / 細菌性肺炎

Outline of Final Research Achievements

Ventilator associated pneumonia (VAP) is an important cause of morbidity and mortality in hospitalized patients. The aim of our study was to investigate whether the innate immune response in the lung critical for the prognosis of VAP. A total of 134 VAP patients was collected, and we found that, late VAP (whose onset was more than 5 days after mechanical ventilation started), occurrence of Adult Respiratory Distress Syndrome(ARDS) in the course of VAP, and VAP caused by gram-negatives, as factors which worsen the prognosis of VAP. Those results suggest that the lung injury in the clinical course of VAP are likely caused by gram-negatives and progress to ARDS lead to poor prognosis. The lung epithelial cell-derived cytokines might be important to protect lungs during VAP.

Research Products

• [Int'l Joint Research] Boston University School of Medicine(米国)
• [Int'l Joint Research] ボストン大学(米国)
• [Int'l Joint Research] Boston University(米国)
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  • Author(s): Tashiro Masato、Fushimi Kiyohide、Kawano Kei、Takazono Takahiro、Saijo Tomomi、Yamamoto Kazuko、Kurihara Shintaro、Imamura Yoshifumi、Miyazaki Taiga、Yanagihara Katsunori、Mukae Hiroshi、Izumikawa Koichi
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  • Journal Title: American Journal of Respiratory Cell Molecular Biology Volume: 55 Issue: 3 Pages: 407-418
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  • Author(s): Nagayoshi Y, Yamamoto K, Hashimoto S, Hisatomi K, Doi S, Nagashima S, Kurohama H, Ito M, Takazono T, Nakamura S, Miyazaki T, Kohno S.
  • Journal Title: Internal Medicine Volume: 55 Issue: 19 Pages: 2849-2853
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• [Journal Article] Relapsed Pulmonary Cryptococcosis during Tumor Necrosis Factor α Inhibitor Treatment (2016)
  • Author(s): Takazono T, Sawai T, Tashiro M, Saijo T, Yamamoto K, Imamura Y, Miyazaki T, Suyama M, Izumikawa K, Kakeya H, Yanagihara K, Mukae H, Kohno S.
  • Journal Title: Internal Medicine Volume: 55 Issue: 19 Pages: 2877-2880
  • DOI: 10.2169/internalmedicine.55.6969
  • NAID: 130005605869
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• [Journal Article] Recurrent <i>Streptococcus agalactiae</i> Toxic Shock Syndrome Triggered by a Tumor Necrosis Factor-α Inhibitor (2016)
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  • Journal Title: Internal Medicine Volume: 55 Issue: 21 Pages: 3211-3214
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• [Journal Article] Epithelial cell-derived secreted and transmembrane 1a (Sectm 1a) signals to activated neutrophils during pneumococcal pneumonia. (2016)
  • Author(s): Kamata H, Yamamoto K, Wasserman GA, Zabinski MC, Yuen CK, Lung WY, Gower AC, Belkina AC, Ramirez MI, Deng JC, Quinton LQ, Jones MR, Mizgerd JP.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: in press
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• [Journal Article] An autopsy case of lepidic pulmonary metastasis from cholangiocarcinoma. (2016)
  • Author(s): Nagayoshi Y, Yamamoto K, Hashimoto S, Hisatomi K, Doi S, Nagashima S, Kurohama H, Ito M, Takazono T, Nakamura S, Miyazaki T, Kohno S.
  • Journal Title: Intern Med. Volume: in press
  • NAID: 130005605839
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oncostatin M induces STAT3-dependent CXCL5 expression and neutrophil recruitment during pneumonia. (2015)
  • Author(s): Traber KE, Hilliard KL, Allen E, Wasserman GA, Yamamoto K, Jones MR, Mizgerd JP, Quinton LJ.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: 53 Issue: 4 Pages: 479-488
  • DOI: 10.1165/rcmb.2014-0342oc
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The lung-liver axis: a requirement for innate immunity and hepatoprotection during pneumonia. (2015)
  • Author(s): Hilliard KL, Allen E, Traber KE, Yamamoto K, Stauffer NM, Wasserman GA, Jones MR, Mizgerd JP, Quinton LJ.
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• [Journal Article] The lung-liver axis facillitates pulmonary innate immunity and hepatoprotection during pneumonia. (2015)
  • Author(s): Hilliard KL., Allen E, Traber KE, Yamamoto K, Stauffer NM, Wasserman GA, Jones MR, Mizgerd JP, Quinton LJ.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Oncostatin M induces STAT3-dependent CXCL5 expression and neutrophil revruitment during pneumonia. (2015)
  • Author(s): Traber KE., Hilliard KL, Allen E, Wasserman GA, Yamamoto K, Jones MR, Mizgerd JP, Quinton LJ.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: in press
  • Peer Reviewed / Open Access
• [Journal Article] Roles of lung epithelium in neutrophil recruitment during pneumococcal pneumonia. (2014)
  • Author(s): Yamamoto K, Ahyi AN, Pepper-Cunningham ZA, Ferrari JD, Wilson AA, Jones MR, Quinton LJ, Mizgerd JP.
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  • DOI: 10.1165/rcmb.2013-0114oc
  • Peer Reviewed / Open Access
• [Presentation] The capacity of pneumococcus to stimulate macrophage NF-kappa B activity dictates the seveerity of adult pneumococcal pneumonia (2018)
  • Author(s): Kazuko Yamamoto, Shuhei Ideguchi, Shotaro Ide, Takahiro Takazono, Tomomi Saijo, Yoshifumi Imamura, Taiga Miyazaki, Katsunori Yanagihara, Yuichi Fukuda, Bin Chang, Fadie T. Coleman, Joseph P. Mizgerd, Hiroshi Mukae
  • Organizer: Gordon Research Conference 2018, Biology of Acute Respiratory Infection
• [Presentation] The impact of neutrophil recruitment in mediastinal lymph node to invasive pneumococcal pneumonia (2018)
  • Author(s): 山本 和子
  • Organizer: 第58回日本呼吸器学会学術講演会
• [Presentation] 縦隔リンパ節内好中球による肺炎球菌肺炎の侵襲性感染症の防御 (2017)
  • Author(s): 山本 和子, 田中 章貴, 田代 将人, 西條 知見, 今村 圭文, 宮崎 泰可, 泉川 公一, 迎 寛
  • Organizer: 第57回日本呼吸器学会学術講演会
• [Presentation] 当科における膿胸の治療経過に関連する患者背景因子の検討 (2017)
  • Author(s): 井手口 周平, 山本 和子, 井手 昇太郎, 田中 章貴, 田代 将人, 小佐井 康介, 賀来 敬仁, 西條 知見, 今村 圭文, 宮崎 泰 可, 泉川 公一, 柳原 克紀, 迎 寛
  • Organizer: 第91回日本感染症学会総会
• [Presentation] Significance of antimicrobial treatment-related factors for the outcomes of adult empyema in Japanese tertiary hospitals (2017)
  • Author(s): Daisuke Okuno, Shuhei Ideguchi, Kazuko Yamamoto, Tomomi Saijo, Yoshifumi Imamura, Taiga Miyazaki, Naoki Iwanaga, Yuichi Fukuda, Kazuhiro Yatera, Hiroshi Mukae
  • Organizer: 30th International Congress of Chemotherapy and Infection 2017
  • Int'l Joint Research
• [Presentation] Resolution of respiratory pneumococcal infection seeds the local lung tissue with CD4+ TRM cells that prevent future pneumonias. (2016)
  • Author(s): Stauffer NM, Coleman FT, Hilliard KL, Yamamoto K, Wasserman G, Dooms H, Jones M, Quinton LJ, Mizgerd JP.
  • Organizer: The 111th American Thoracic Society 2016 International Conference
  • Place of Presentation: San Francisco, USA.
  • Year and Date: 2016-05-17
  • Int'l Joint Research
• [Presentation] Characterizing secondary pneumococcal superinfection following seasonal influenza virus. (2016)
  • Author(s): Ota K, Yamamoto K, Iwanaga N, Nagayoshi Y, Yamasaki K, Miyazaki T, Mukae H, Yanagihara K, Ashizawa K, Kohno S.
  • Organizer: The 111th American Thoracic Society 2016 International Conference
  • Place of Presentation: San Francisco, USA.
  • Year and Date: 2016-05-16
  • Int'l Joint Research
• [Presentation] 肺炎球菌肺炎と自然免疫応答 (2016)
  • Author(s): 山本和子
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-08
• [Presentation] 肺炎球菌肺炎のインフルエンザ感染合併の有無による臨床的特徴の差異に関する検討 (2016)
  • Author(s): 太田賢治, 山本和子, 岩永直樹, 永吉洋介, 久冨恵子, 土井誠志, 長島聖二, 山崎一美, 柳原克紀, 河野 茂
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-08
• [Presentation] 当院におけるS.maltophiliaの現状と予後因子に関する検討. (2015)
  • Author(s): 太田賢治, 永吉洋介, 大野直義, 山本和子, 河野茂.
  • Organizer: 第69回国立病院総合医学会.
  • Place of Presentation: 札幌
  • Year and Date: 2015-10-02
• [Presentation] Prognostic factors of patients with ventilator-associated pneumonia in ICU. D22. Nosocomial and fungal infections. (2015)
  • Author(s): Ota K, Yamamoto K, Nagayoshi Y, Hisatomi K, Doi S, Nagashima S, Yamasaki K, Takayama H, Kohno S.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-20
  • Int'l Joint Research
• [Presentation] Prognostic Factors of Patients with Ventilator-Associated Pneumonia in ICU (2015)
  • Author(s): K. Ota, K. Yamamoto, Y. Nagayoshi, K. Hisatomi, S. Doi, S. Nagashima, K. Yamasaki, H. Takayama, S. Kohno.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-20
• [Presentation] Respiratory infections with pneumococci establish multi-pronged heterotypic immunity that protects against pneumonia. (2015)
  • Author(s): Stauffer NM, Coleman FT, Hilliard KL, Yamamoto K, Zabinski MC, Jones MR, Quinton LJ, Mizgerd JP.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-19
  • Int'l Joint Research
• [Presentation] Respiratory Infections with Pneumococci Establish Multi-Pronged Heterotypic Immunity that Protects Against Pneumonia. (2015)
  • Author(s): N.M. Stauffer, F.T. Coleman, K.L. Hilliard, K. Yamamoto, M.C. Zabinski, M.R. Jones, L.J. Quinton, J.P. Mizgerd.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-19
• [Presentation] Secreted and transmembrane 1a (Sectm1a) from pulmonary epithelial cells enhances phagocyte recruitment during pneumonia. (2015)
  • Author(s): Kamata H, Yamamoto K, Wasserman GA, Zabinski MC, Quinton LJ, Jones MR, Mizgerd JP.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-18
  • Int'l Joint Research
• [Presentation] Macrophage necroptosis and pneumonia caused by virulent pneumococcus. (2015)
  • Author(s): Coleman FT, Blahna MT, Pepper-Cunningham ZA, Zabinski MC, Yamamoto K, Wilson AA, Quinton LJ, Jones MR, Kotton DN, Pelton SI, Mizgerd JP.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-18
  • Int'l Joint Research
• [Presentation] Macrophage Necroptosis and Pneumonia Caused by Virulent Pneumococcus. (2015)
  • Author(s): F.T. Coleman, M.T. Blahna, Z.A. Pepper-Cunningham, M.C. Zabinski, K. Yamamoto, A.A. Wilson, L.J. Quinton, M.R. Jones, D.N. Kotton, S.I. Pelton, J.P. Mizgerd.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-18
• [Presentation] Secreted and Transmembrane 1a (Sectm1a) from Pulmonary Epithelial Cells Enhances Phagocyte Recruitment During Pneumonia. (2015)
  • Author(s): H. Kamata, K. Yamamoto, G.A. Wasserman, M.C. Zabinski, L.J. Quinton, M.R. Jones, J.P. Mizgerd.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-18
• [Presentation] Oncostatin M induces STAT3-dependent CXCL5 expression in lung epithelium to increase neutrophil recruitment during pneumonia. (2015)
  • Author(s): Traber KE, Hilliard KL, Allen E, Wasserman GA, Yamamoto K, Jones MR, Mizgerd JP, Quinton LJ.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Presentation] Oncostatin M Induces STAT3-Dependent CXCL5 Expression in Lung Epithelium to Increase Neutrophil Recruitment During Pneumonia (2015)
  • Author(s): K.E. Traber, K.L. Hilliard, E. Allen, G.A. Wasserman, K. Yamamoto, M.R. Jones, J.P. Mizgerd, L.J. Quinton.
  • Organizer: The 110th American Thoracic Society 2015 International Conference.
  • Place of Presentation: Denver, USA.
  • Year and Date: 2015-05-17
• [Presentation] 肺感染症と肺上皮細胞免疫. シンポジウム｢呼吸器疾患の免疫治療を考える｣. (2015)
  • Author(s): 山本和子.
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-19
• [Presentation] 肺感染症と肺上皮細胞免疫 (2015)
  • Author(s): 山本和子
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-19
  • Invited
• [Presentation] Neutrophil recruitment to mediastinal lymph nodes prevents bacteremia during pneumonia. (2015)
  • Author(s): Yamamoto K, Mizgerd JP, Kohno S.
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-18
• [Presentation] 当院で分離されたStenotrophomonas maltophiliaの特徴と予後因子に関する検討 (2015)
  • Author(s): 太田賢治, 永吉洋介, 大野直義, 山本和子, 河野茂.
  • Organizer: 第89回日本感染症学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2015-04-17
• [Presentation] Prognostic factors of patients with ventilator-associated pneumonia in ICU. (2014)
  • Author(s): 太田賢治, 山本和子, 永吉洋介, 久冨恵子, 土井誠志, 長島聖二, 山崎一美, 高山隼人.
  • Organizer: 第68回国立病院総合医学会.
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-14
• [Presentation] 急性脳卒中における肺炎. (2014)
  • Author(s): 高畠英昭, 山本和子.
  • Organizer: 第88回日本感染症学会総会.
  • Place of Presentation: 福岡
  • Year and Date: 2014-06-18
• [Presentation] 長崎医療センターにおける人工呼吸器関連肺炎の検討. (2014)
  • Author(s): 太田賢治, 山本和子, 迎祐太, 多田紗希子, 永吉洋介, 久冨恵子, 土井誠志, 長島聖二, 山崎一美, 高山隼人, 河野茂.
  • Organizer: 第88回日本感染症学会総会.
  • Place of Presentation: 福岡
  • Year and Date: 2014-06-18
• [Presentation] Alveolar Macrophage NF-κB-driven Lung Defense Is Circumvented By Virulent Pneumococci (2014)
  • Author(s): Coleman FT, Blahna MT, Ferrari JD, Pepper-Cinningham ZA, Yamamoto K, Wilson AA, Quinton LJ, Jones MR, Kotton DN, Pelton SI, Mizgerd JP.
  • Organizer: The 109th American Thoracic Society 2014 International Conference.
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2014-05-20
• [Presentation] Respiratory exposures to pneumococcus confer Th17 memory and heterotipic lung protection. (2014)
  • Author(s): Stauffer NM, Coleman FT, Hilliard KL, Yamamoto K, Zabinski M, Jones MR, Quinton LJ, Mizgerd JP.
  • Organizer: The 109th American Thoracic Society 2014 International Conference.
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2014-05-20
• [Presentation] Neutrophil recruitment to mediastinal lymph nodes prevents bacteremia during pneumonia. (2014)
  • Author(s): Yamamoto K, Ahyi ANN, Stauffer NM, Pepper-Cunningham ZA, Jones MR, Quinton LJ, Mizgerd JP.
  • Organizer: The 109th American Thoracic Society 2014 International Conference.
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2014-05-19
• [Presentation] The Lung-Liver Axis Facilitates Innate Immunity And Survival During Pneumonia. (2014)
  • Author(s): Hilliard KL, Allen E, Traber KE, Yamamoto K, Stauffer NM, Jones MR, Mizgerd JP, Quinton LJ.
  • Organizer: The 109th American Thoracic Society 2014 International Conference.
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2014-05-19
• [Presentation] Oncostatin M is required for maximal CXCL5 expression and neutrophil recruitment during pneumonia. (2014)
  • Author(s): Traber KE, Aleen E, Hilliard KL, Yamamoto K, Jones MR, Mizgerd JP, Quinton LJ.
  • Organizer: The 109th American Thoracic Society 2014 International Conference.
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2014-05-18
• [Presentation] Epithelial-Specific Immune Responses During Pneumonia. (2014)
  • Author(s): Kamata H, Yamamoto K, Wasserman GA, Zabinski MC, Quinton LJ, Jones MR, Mizgerd JP.
  • Organizer: The 109th American Thoracic Society 2014 International Conference.
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2014-05-18
• [Presentation] 肺上皮細胞はいかにして感染症と戦うか. (2014)
  • Author(s): 山本和子
  • Organizer: 第11回肺研究フォーラム.
  • Place of Presentation: 大阪
  • Year and Date: 2014-04-25
• [Book] 炎症と免疫 (2016)
  • Author(s): 山本和子、迎 寛.
  • Publisher: 先端医学社
• [Book] 化学療法の領域 (2016)
  • Author(s): 山本和子、迎 寛.
  • Publisher: 医薬ジャーナル社
• [Book] 特集/呼吸器病学TOPICS 2014-15 (2015)
  • Author(s): 山本和子
  • Total Pages: 4
  • Publisher: 先端医学社
• [Book] 分子呼吸器病 (2015)
  • Author(s): 山本和子
  • Total Pages: 4
  • Publisher: 先端医学社