Comprehensive approaches to pathopysiology and better treatment among severe asthma

• Project/Area Number: 15K09189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyorin University
• Principal Investigator: Takizawa Hajime 杏林大学, 医学部, 教授 (80171578)
• Co-Investigator(Kenkyū-buntansha): 渡辺 雅人 杏林大学, 医学部, 学内講師 (00458902) ; 皿谷 健 杏林大学, 医学部, 講師 (40549185) ; 田村 仁樹 杏林大学, 医学部, 助教 (80616607)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 難治性喘息 / 気道炎症 / 細胞内シグナル / 抗炎症薬 / 増悪 / バイオマーカー / 好中球性炎症 / 自然免疫 / ウイルス感染症 / マクロライド薬 / ST2

Outline of Final Research Achievements

Inhaled corticosteroid therapy has improved asthma control, but 5~10% of the patients still experience frequent exacerbations. We performed basic and clinical approaches to improve patients care and outcome among severe asthma. In vitro studies using airway epithelial cell culture showed that virus analogue poly(I:C) strongly induced CCL5 expression and release of its protein that has been believed to play an important role in asthma exacerbation. Potent anti-asthma drug fluticasone attenuated the process. Clinical studies indicated that oxidant marker H2O2 and soluble ST2 are potential biomarkers of exacerbations. Further verification studies might help improve care and treatment for the patients with severe asthma.

Research Products

• [Journal Article] Asthma phenotypes: An important step for tailor-made therapy (2017)
  • Author(s): Nakamoto Keitaro、Saraya Takeshi、Takizawa Hajime
  • Journal Title: Journal of General and Family Medicine Volume: 18 Issue: 5 Pages: 315-316
  • DOI: 10.1002/jgf2.72
  • Peer Reviewed / Open Access
• [Journal Article] The molecular epidemiology of respiratory viruses associated with asthma attacks: A single-center observational study in Japan. (2017)
  • Author(s): Saraya T, Kimura H, Kurai D, Ishii H, Takizawa H.
  • Journal Title: Medicine (Baltimore). Volume: 96 Issue: 42 Pages: 1-7
  • DOI: 10.1097/md.0000000000008204
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum Reactive Oxygen Metabolite Levels Predict Severe Exacerbations of Asthma. (2016)
  • Author(s): Nakamoto K, Watanabe M, Sada M, Inui T, Nakamura M, Honda K, Wada H, Mikami Y, Matsuzaki H, Horie M, Noguchi S, Yamauchi Y, Koyama H, Kogane T, Kohyama T, Takizawa H.
  • Journal Title: PLoS One Volume: - Issue: 10 Pages: e0164948-e0164948
  • DOI: 10.1371/journal.pone.0164948
  • Peer Reviewed / Open Access
• [Journal Article] IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation. (2016)
  • Author(s): Honda K, Wada H, Nakamura M, Nakamoto K, Inui T, Sada M, Koide T, Takata S, Yokoyama T, Saraya T, Kurai D, Ishii H, Goto H, Takizawa H
  • Journal Title: Exp Lung Res Volume: 42 Issue: 4 Pages: 205-16
  • DOI: 10.1080/01902148.2016.1190796
  • Peer Reviewed
• [Journal Article] Experimental Lung Research (2015)
  • Author(s): Manabu Higaki, Hiroo Wada, Shin-ichiro Mikura, Tetsuo Yasutake, Masuo Nakamura, Mamoru Niikura, Fumie Kobayashi, Hiroshi Kamma, Shigeru Kamiya, Kazuhiro Ito, Peter Barnes, Hajime Goto, Hajime Takizawa
  • Journal Title: IL-10 modulates pulmonary neutrophilic inflammation induced by cigarette smoke exposure Volume: 41 Issue: 10 Pages: 525-534
  • DOI: 10.3109/01902148.2015.1096315
  • Peer Reviewed
• [Journal Article] Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice. (2015)
  • Author(s): Nakamura M, Wada H, Honda K, Nakamoto K, Inui T, Sada M, Watanabe M, Takata S, Yokoyama T, Saraya T, Kurai D, Ishii H, Goto H, Kamma H, Takizawa H.
  • Journal Title: Pulm Pharmacol Ther. Volume: 35 Pages: 60-66
  • DOI: 10.1016/j.pupt.2015.09.005
  • Peer Reviewed
• [Presentation] Bacterial and Viral Infection Enhances sST2 Production by Bronchial Epithelial Cells. (2017)
  • Author(s): Watanabe M, Nakamoto K, Sada M, Inui T, Takata S, Yokoyama T, Saraya T, Ishii H, Takizawa H
  • Organizer: American Thoracic Society 2017 International Conference, Washington
  • Int'l Joint Research
• [Presentation] Serum sST2 Levels Predict Severe Exacerbation of Asthma: A Potential Implication for Neutrophilic Asthma. (2017)
  • Author(s): Watanabe M, Nakamoto K, Sada M, Inui T, Takata S, Yokoyama T, Saraya T, Kurai D, Ishii H, Takizawa H
  • Organizer: American Thoracic Society 2017 International Conference, Washington
  • Int'l Joint Research
• [Presentation] 成人喘息 病態 気道上皮細胞におけるウイルス感染時のCCL5の発現とその制御機構の基礎的検討 (2017)
  • Author(s): 佐田充，渡辺雅人，乾俊哉，中本啓太郎，滝澤始
  • Organizer: 第66回日本アレルギー学会学術大会，東京
• [Presentation] LPS刺激による気道上皮細胞からのCXCL1産生 (2017)
  • Author(s): 乾俊哉，渡辺雅人，佐田充，中本啓太郎，中村益夫，本多紘二郎，小川ゆかり，田村仁樹，横山琢磨，倉井大輔，皿谷健，石井晴之，滝澤始
  • Organizer: 第66回日本感染症学会東日本地方会学術集会・第64回日本化学療法学会東日本支部総会合同学会，東京
• [Presentation] Reactive oxygen metabolite levels are surrogate biomarkers for predicting exacerbation of bronchial asthma. (2016)
  • Author(s): Nakamoto k, Watanabe M, Sada M, Inui T, Ogawa Y, Nakamura M, Honda K, Koide T, Takata S, Yokoyama T, Saraya T, Kurai D, Wada H, Ishii H, Takizawa H
  • Organizer: ERS International Congress 2016
  • Place of Presentation: ロンドン、イギリス
  • Year and Date: 2016-09-03
  • Int'l Joint Research
• [Presentation] Regulation of GROα production in human bronchial epithelial cells. (2016)
  • Author(s): Inui T, Watanabe M, Nakamoto K, Sada M, Tsuji S, Hirata A, Nakamura M, Ogawa Y, Koide T, Takata S, Yokoyama T, Kurai D, Saraya T, Ishii H, Wada H, Takizawa H
  • Organizer: ERS International Congress 2016
  • Place of Presentation: ロンドン、イギリス
  • Year and Date: 2016-09-03
  • Int'l Joint Research
• [Presentation] Upregulation of CCL5 production in the airway epithelium at the time of the viral infection. (2016)
  • Author(s): Sada M, Watanabe M, Inui T, Nakamoto K, Nakamura M, Matsuzaki H, Yamauchi Y, Takizawa H
  • Organizer: ERS International Congress 2016
  • Place of Presentation: ロンドン、イギリス
  • Year and Date: 2016-09-03
  • Int'l Joint Research
• [Presentation] Oxidative stress and biomarkers in patients with bronchial asthma. (2015)
  • Author(s): Keitaro Nakamoto, Keitaro Nakamoto, Hiroo Wada, Shingo Tsuji, Mitsuru Sada, Toshiya Inui, Masuo Nakamura, Kojiro Honda, Yasutaka Tanaka, Takashi Koide, Saori Takata, Masato Watanabe, Takuma Yokoyama, Takeshi Saraya, Daisuke Kurai, Haruyuki Ishii, Hajime Takizawa
  • Organizer: European Respiratory Society International Congress
  • Place of Presentation: Amsterdam RAI, Netherands
  • Year and Date: 2015-09-26
  • Int'l Joint Research
• [Book] PM2.5: Role of Oxidative Stress in Health Effects and Prevention Strategy (2015)
  • Author(s): Li YJ, Takizawa H, Azuma A, Kawada T.
  • Total Pages: 15
  • Publisher: Nova Science Publishers, Inc.