Study on the refractory mechanism in inflammatory obstructive lung disease

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15K09233
• Research Institution: Jikei University School of Medicine
• Principal Investigator: 中山 勝敏 東京慈恵会医科大学, 医学部, 准教授 (40321989)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 喘息 / COPD / 難治化 / ヒト ヘルペス ウイルス / 抗SITH-1抗体 / 好酸球性副鼻腔炎 / 術後合併症

Outline of Annual Research Achievements

本年度は2つの研究を行った。
研究1： HHV-6再活性化により嗅球で発現するSITH-1蛋白に対する抗体(S1 Ab)陽性は精神的疲労と関連する。今回、特に喘息患者でのS1 Ab (+)と増悪の関連およびS1 Ab (+)となる要因を検討した。増悪リスクに対しS1 Ab (+)を含む各種要因による多変量解析の結果、喘息重症度とS1 Ab (+)が有意な関連を示した[OR(CI)= 37.7 (3.0-475.0); OR(CI)=12.7 (1.3-129.2)]。また、S1 Ab (+)に対する各種要因による多変量解析の結果、好酸球性副鼻腔炎が有意な関連を示した[OR(CI)= 16.6(1.8-152.7)]。喘息では、S1 Ab (+)は増悪に関与する可能性があり、S1 Ab (+)の要因として好酸球性副鼻腔炎が考えられた。
研究2：COPD、喘息患者での術後肺合併症(PPC)発症リスクを検討した。2014年4月から1年間に大学病院で非肺手術を受けた喘息257名、COPD 89名(計346名)を対象とし、各種要因を遡及的に評価した。PPCは喘息22例、COPD 7例が発症。多変量解析の結果、喘息では喫煙指数≧20 P-Y、末血Eo数≧200、STEP≧3がPPCと有意に関連していた[OR(CI)= 5.4(1.4-20.8); 0.31(0.11-0.84); 3.2(1.04-9.9)]。COPDでは、年、COPD治療導入、上腹部手術、手術時間≧5hがPPCと有意に関連していた[OR(CI)= 1.18(1.00-1.40), 0.09(0.01-0.81), 21.2(1.3-349), 9.5(1.2-77.4)]。危険因子として、喘息では、重喫煙と高重症度、COPDでは、高齢、腹部また長時間手術があげられた。一方、好酸球性喘息でのICS治療およびCOPDでの治療の導入は、PPC減少に寄与する可能性が示された。

Research Products

• [Journal Article] Risk factors of postoperative pulmonary complications in patients with asthma and COPD. (2018)
  • Author(s): Numata T, Nakayama K, Fujii S, Yumino Y, Saito N, Yoshida M, Kurita Y, Kobayashi K, Ito S, Utsumi H, Yanagisawa H, Hashimoto M, Wakui H, Minagawa S, Ishikawa T, Hara H, Araya J, Kaneko Y, Kuwano K.
  • Journal Title: BMC Pulm Med. Volume: 18 Pages: -
  • DOI: 10.1186/s12890-017-0570-8
  • Peer Reviewed / Open Access
• [Journal Article] Detection of pathogens by real-time PCR in adult patients with acute exacerbation of bronchial asthma. (2017)
  • Author(s): Yoshii Y, Shimizu K, Morozumi M, Chiba N, Ubukata K, Uruga H, Hanada S, Wakui H, Minagawa S, Hara H, Numata T, Saito K, Araya J, Nakayama K, Kishi K, Kuwano K.
  • Journal Title: BMC Pulm Med. Volume: 17 Pages: -
  • DOI: 10.1186/s12890-017-0494-3
  • Peer Reviewed / Open Access
• [Journal Article] Macroscopic inflammatory tracheal and endobronchial nodules in Sjoegren's syndrome. (2017)
  • Author(s): Hara H, Kuwano K, Minagawa S, Numata T, Araya J, Nakayama K.
  • Journal Title: Thorax. Volume: 72 Pages: 864-865
  • DOI: 10.1136/thoraxjnl-2016-209390
  • Peer Reviewed
• [Journal Article] Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4. (2017)
  • Author(s): Tsubouchi K, Araya J, Minagawa S, Hara H, Ichikawa A, Saito N, Kadota T, Sato N, Yoshida M, Kurita Y, Kobayashi K, Ito S, Fujita Y, Utsumi H, Yanagisawa H, Hashimoto M, Wakui H, Yoshii Y, Ishikawa T, Numata T, Kaneko Y, Asano H, Yamashita M, Odaka M, Morikawa T, Nakayama K, Nakanishi Y, Kuwano K.
  • Journal Title: Autophagy. Volume: 13 Pages: 1420-1434
  • DOI: 10.1080/15548627.2017.1328348
  • Peer Reviewed
• [Journal Article] Pirfenidone inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy. (2017)
  • Author(s): Kurita Y, Araya J, Minagawa S, Hara H, Ichikawa A, Saito N, Kadota T, Tsubouchi K, Sato N, Yoshida M, Kobayashi K, Ito S, Fujita Y, Utsumi H, Yanagisawa H, Hashimoto M, Wakui H, Yoshii Y, Ishikawa T, Numata T, Kaneko Y, Asano H, Yamashita M, Odaka M, Morikawa T, Nakayama K, Kuwano K.
  • Journal Title: Respir Res. Volume: 18 Pages: -
  • DOI: 10.1186/s12931-017-0600-3
  • Peer Reviewed / Open Access
• [Presentation] Role of lamin B1 in COPD pathogenesis. (2017)
  • Author(s): Nayuta Saito, Katsutoshi Nakayama, et al.
  • Organizer: European Respiratory Society International Congress 2017
  • Int'l Joint Research
• [Presentation] PARK2-regulated mitophagy in COPD pathogenesis. (2017)
  • Author(s): Nahoko Sato, Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Nayuta Saito, Masahiro Yoshida, Yusuke Kurita, Kenji Kobayashi, Saburo Ito, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Katsutoshi Nakayama, Hirotsugu Kohrogi, Kazuyoshi Kuwano.
  • Organizer: European Respiratory Society International Congress 2017
  • Int'l Joint Research
• [Presentation] Azithromycin-mediated CHIP regulation promotes proteasomal degradation of NOX4. (2017)
  • Author(s): Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Nayuta Saito, Akihiro Ichikawa, Nahoko Sato, Masahiro Yoshida, Yusuke Kurita, Takanori Numata, Yumi Kaneko, Katsutoshi Nakayama, Kazuyoshi Kuwano.
  • Organizer: European Respiratory Society International Congress 2017
  • Int'l Joint Research
• [Presentation] Involvement ferroptosis in COPD pathogenesis. (2017)
  • Author(s): Masahiro Yoshida (Tokyo, Japan), Shunsuke Minagawa, Jun Araya, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Nahoko Sato, Kazuya Tsubouchi, Yusuke Kurita, Takanori Numata, Yumi Kaneko, Katsutoshi Nakayama, Kazuyoshi Kuwano.
  • Organizer: European Respiratory Society International Congress 2017
  • Int'l Joint Research