肥満喘息の難治化メカニズムと新規治療基盤の創出

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19K17632
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: 鈴木 勇三 浜松医科大学, 医学部, 助教 (00758435)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Autophagy / 肥満喘息 / 気道上皮 / IL-33 / TSLP

Outline of Annual Research Achievements

肥満は喘息患者に高頻度に見られ，肥満喘息は重症喘息の中で最も難治な一群である．肥満喘息は非肥満喘息と同様に均一な病態でなく，Th2-lowやTh2-highなど種々に分類されるとされているが，その病態は十分に解明されていない． そこで，本研究では肥満喘息におけるオートファジーの意義を明らかにすることを目的とした．全身性および気道上皮特異的Atg5-/-マウスを用いた.肥満喘息モデルは，高脂肪食を16週間負荷した後にHDM感作を行い作成した．肥満Atg5-/-マウスは肥満野生型マウスと比較して，BAL中の好酸球数の上昇と気道過敏性亢進が認められ，これらはステロイド抵抗性であった．オートファジー欠損で誘導される肥満喘息モデルで好酸球炎症や気道過敏性亢進は，bone marrow transfer modelでも確認された．肥満Atg5-/-マウス肺の解析では，肥満Atg5-/-マウス肺内のTh2細胞が増加していたが，ILC2s数は肥満野生型マウスと同等であった．気道上皮特異的肥満Atg5-/-マウスでもBAL中の好酸球上昇が確認された．肥満Atg5-/-マウス気道上皮ではTSLPおよびIL-33発現が亢進し，肥満Atg5-/-マウスの好酸球炎症と気道過敏性はTSLP依存性，IL-33に抑制された．これらの結果から，オートファジー制御は肥満喘息の新規治療標的となりうると考えられた．

Research Products

• [Journal Article] Involvement of autophagy in exacerbation of eosinophilic airway inflammation in a murine model of obese asthma (2022)
  • Author(s): Suzuki Yuzo、Aono Yuya、Akiyama Norimichi、Horiike Yasuoki、Naoi Hyogo、Horiguchi Ryo、Shibata Kiyoshi、Hozumi Hironao、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Autophagy Volume: － Pages: 1～13
  • DOI: 10.1080/15548627.2022.2025571
  • Peer Reviewed / Open Access
• [Journal Article] Impact of antifibrotic therapy on lung cancer development in idiopathic pulmonary fibrosis (2022)
  • Author(s): Naoi Hyogo、Suzuki Yuzo、Mori Kazutaka、Aono Yuya、Kono Masato、Hasegawa Hirotsugu、Yokomura Koshi、Inoue Yusuke、Hozumi Hironao、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Nakamura Yutaro、Inui Naoki、Nakamura Hidenori、Suda Takafumi
  • Journal Title: Thorax Volume: in press Pages: －
  • DOI: 10.1136/thoraxjnl-2021-218281
  • Peer Reviewed
• [Journal Article] Impact of end-of-life respiratory modalities on quality of dying and death and symptom relief in patients with interstitial lung disease: a multicenter descriptive cross-sectional study (2022)
  • Author(s): Koyauchi Takafumi, Suzuki Yuzo, Sato Kazuki, Hozumi Hironao, Karayama Masato, Furuhashi Kazuki, Fujisawa Tomoyuki, Enomoto Noriyuki, Nakamura Yutaro, Inui Naoki, Yokomura Koshi, Imokawa Shiro, Nakamura Hidenori, Morita Tatsuya, Suda Takafumi
  • Journal Title: Respiratory Research Volume: in press Pages: －
  • DOI: 10.1186/s12931-022-02004-x.
  • Peer Reviewed / Open Access
• [Journal Article] Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: mortality and its prediction model (2022)
  • Author(s): Hozumi Hironao, Kono Masato, Hasegawa Hirotsugu, Kato Shinpei, Inoue Yusuke, Suzuki Yuzo, Karayama Masato, Furuhashi Kazuki, Enomoto Noriyuki, Fujisawa Tomoyuki, Inui Naoki, Nakamura Yutaro, Yokomura Koshi, Nakamura Hidenori, Suda Takafumi
  • Journal Title: Respiratory Research Volume: in press Pages: －
  • DOI: 10.1186/s12931-022-01978-y.
  • Peer Reviewed / Open Access
• [Journal Article] Transient leukocytopenia following combination therapy for COVID-19 (2022)
  • Author(s): Tsuchiya Kazuo、Fujisawa Tomoyuki、Mochizuka Yasutaka、Takuma Sho、Oishi Kyohei、Endo Yoshinari、Tanaka Yuko、Fukada Atsuki、Watanabe Hirofumi、Katsumata Mineo、Aoshima Yoichiro、Inoue Yusuke、Suzuki Yuzo、Karayama Masato、Hozumi Hironao、Furuhashi Kazuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Respiratory Investigation Volume: 60 Pages: 158～161
  • DOI: 10.1016/j.resinv.2021.09.007
  • Peer Reviewed
• [Journal Article] Combined assessment of the GAP index and body mass index at antifibrotic therapy initiation for prognosis of idiopathic pulmonary fibrosis (2021)
  • Author(s): Suzuki Yuzo、Mori Kazutaka、Aono Yuya、Kono Masato、Hasegawa Hirotsugu、Yokomura Koshi、Naoi Hyogo、Hozumi Hironao、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Nakamura Yutaro、Inui Naoki、Nakamura Hidenori、Suda Takafumi
  • Journal Title: Scientific Reports Volume: 11 Pages: －
  • DOI: 10.1038/s41598-021-98161-y
  • Peer Reviewed / Open Access
• [Journal Article] Switching antifibrotics in patients with idiopathic pulmonary fibrosis: a multi-center retrospective cohort study (2021)
  • Author(s): Suzuki Yuzo、Mori Kazutaka、Aono Yuya、Kono Masato、Hasegawa Hirotsugu、Yokomura Koshi、Naoi Hyogo、Hozumi Hironao、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Nakamura Yutaro、Inui Naoki、Nakamura Hidenori、Suda Takafumi
  • Journal Title: BMC Pulmonary Medicine Volume: 21 Pages: －
  • DOI: 10.1186/s12890-021-01587-3
  • Peer Reviewed / Open Access
• [Journal Article] Association of the Geriatric Nutritional Risk Index with the survival of patients with non-small-cell lung cancer after platinum-based chemotherapy (2021)
  • Author(s): Karayama Masato、Inoue Yusuke、Yasui Hideki、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: BMC Pulmonary Medicine Volume: 21 Pages: －
  • DOI: 10.1186/s12890-021-01782-2
  • Peer Reviewed / Open Access
• [Journal Article] Prophylactic granulocyte-colony stimulating factor in patients with lung neuroendocrine carcinoma receiving platinum agents plus etoposide (2021)
  • Author(s): Watanabe Hirofumi、Karayama Masato、Yasui Hideki、Inoue Yusuke、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Cancer Treatment and Research Communications Volume: 29 Pages: 100493～100493
  • DOI: 10.1016/j.ctarc.2021.100493
  • Peer Reviewed / Open Access
• [Journal Article] Radiological pleuroparenchymal fibroelastosis-like lesion in idiopathic interstitial pneumonias (2021)
  • Author(s): Fujisawa Tomoyuki、Horiike Yasuoki、Egashira Ryoko、Sumikawa Hiromitsu、Iwasawa Tae、Matsushita Shoichiro、Sugiura Hiroaki、Kataoka Kensuke、Hashisako Mikiko、Yasui Hideki、Hozumi Hironao、Karayama Masato、Suzuki Yuzo、Furuhashi Kazuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Respiratory Research Volume: 22 Pages: －
  • DOI: 10.1186/s12931-021-01892-9
  • Peer Reviewed / Open Access
• [Journal Article] Association of the Geriatric Nutritional Risk Index With the Survival of Patients With Non?Small Cell Lung Cancer After Nivolumab Therapy (2021)
  • Author(s): Karayama Masato、Inoue Yusuke、Yoshimura Katsuhiro、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Journal of Immunotherapy Volume: 45 Pages: 125～131
  • DOI: 10.1097/CJI.0000000000000396
  • Peer Reviewed
• [Journal Article] Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with uncommon histology: a propensity-score-matched analysis (2021)
  • Author(s): Miyashita K、Karayama M、Inoue Y、Hozumi H、Suzuki Y、Furuhashi K、Fujisawa T、Enomoto N、Nakamura Y、Kono M、Matsui T、Niwa M、Koda K、Toyoshima M、Matsushima S、Matsuura S、Asada K、Fujii M、Kusagaya H、Matsuda H、Inui N、Suda T
  • Journal Title: BMC Pulmonary Medicine Volume: 21 Pages: －
  • DOI: 10.1186/s12890-021-01681-6
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic and prognostic significance of serum angiopoietin-1 and -2 concentrations in patients with pulmonary hypertension (2021)
  • Author(s): Enomoto Noriyuki、Suzuki Seiichiro、Hozumi Hironao、Karayama Masato、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Nakamura Yutaro、Odagiri Keiichi、Ishikawa Takamichi、Kataoka Kensuke、Kondoh Yasuhiro、Maekawa Masato、Inui Naoki、Watanabe Hiroshi、Suda Takafumi
  • Journal Title: Scientific Reports Volume: 11 Pages: －
  • DOI: 10.1038/s41598-021-94907-w
  • Peer Reviewed / Open Access
• [Journal Article] Comparative assessment of NOIR-SS and ddPCR for ctDNA detection of EGFR L858R mutations in advanced L858R-positive lung adenocarcinomas (2021)
  • Author(s): Akahori Daisuke、Inoue Yusuke、Inui Naoki、Karayama Masato、Yasui Hideki、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Suda Takafumi
  • Journal Title: Scientific Reports Volume: 11 Pages: －
  • DOI: 10.1038/s41598-021-94592-9
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Significance of Cold-Inducible RNA-Binding Protein in Idiopathic Pulmonary Fibrosis (2021)
  • Author(s): Hozumi Hironao、Kataoka Kensuke、Kondoh Yasuhiro、Isayama Takuya、Okada Jun、Sugiura Katsunori、Mori Kazutaka、Kono Masato、Suzuki Yuzo、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Inui Naoki、Nakamura Yutaro、Suda Takafumi
  • Journal Title: Chest Volume: 160 Pages: 2149～2157
  • DOI: 10.1016/j.chest.2021.06.067
  • Peer Reviewed
• [Journal Article] Serum S100A8 and S100A9 as prognostic biomarkers in acute exacerbation of idiopathic pulmonary fibrosis (2021)
  • Author(s): Tanaka Kazuki、Enomoto Noriyuki、Hozumi Hironao、Isayama Takuya、Naoi Hyogo、Aono Yuya、Katsumata Mineo、Yasui Hideki、Karayama Masato、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Inui Naoki、Nakamura Yutaro、Suda Takafumi
  • Journal Title: Respiratory Investigation Volume: 59 Pages: 827～836
  • DOI: 10.1016/j.resinv.2021.05.008
  • Peer Reviewed
• [Journal Article] Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer (2021)
  • Author(s): Karayama M、Inui N、Inoue Y、Yoshimura K、Mori K、Hozumi H、Suzuki Y、Furuhashi K、Fujisawa T、Enomoto N、Nakamura Y、Asada K、Uto T、Fujii M、Matsui T、Matsuura S、Hashimoto D、Toyoshima M、Kusagaya H、Matsuda H、Inami N、Kaida Y、Niwa M、Ito Y、Suda T
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 71 Pages: 203～217
  • DOI: 10.1007/s00262-021-02979-4
  • Peer Reviewed
• [Journal Article] Prognostic and Clinical Value of Cluster Analysis in Idiopathic Pleuroparenchymal Fibroelastosis Phenotypes (2021)
  • Author(s): Nakamura Y、Mori K、Enomoto Y、Kono M、Sumikawa H、Johkoh T、Colby TV.、Yasui H、Hozumi H、Karayama M、Suzuki Y、Furuhashi K、Fujisawa T、Enomoto N、Inui、Kaida Y、Yokomura K、Koshimizu N、Toyoshima M、Imokawa S、Yamada T、Shirai T、Nakamura H、Hayakawa H、Suda T
  • Journal Title: Journal of Clinical Medicine Volume: 10 Pages: 1498～1498
  • DOI: 10.3390/jcm10071498
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic classification in acute exacerbation of idiopathic pulmonary fibrosis: a multicentre retrospective cohort study (2021)
  • Author(s): Suzuki Takahito、Hozumi Hironao、Miyashita Koichi、Kono Masato、Suzuki Yuzo、Karayama Masato、Furuhashi Kazuki、Hasegawa Hirotsugu、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Yokomura Koshi、Nakamura Hidenori、Suda Takafumi
  • Journal Title: Scientific Reports Volume: 11 Pages: －
  • DOI: 10.1038/s41598-021-88718-2
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of peripheral blood monocyte and neutrophil counts in rheumatoid arthritis-associated interstitial lung disease (2021)
  • Author(s): Saku Aiko、Fujisawa Tomoyuki、Nishimoto Koji、Yoshimura Katsuhiro、Hozumi Hironao、Karayama Masato、Suzuki Yuzo、Furuhashi Kazuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Respiratory Medicine Volume: 182 Pages: 106420～106420
  • DOI: 10.1016/j.rmed.2021.106420
  • Peer Reviewed
• [Journal Article] Simple method for detecting idiopathic interstitial pneumonias by measuring vertical lung length on chest X-ray (2021)
  • Author(s): Karayama Masato、Aoshima Yoichiro、Yasui Hideki、Hozumi Hironao、Suzuki Yuzo、Furuhashi Kazuki、Fujisawa Tomoyuki、Enomoto Noriyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Scientific Reports Volume: 11 Pages: －
  • DOI: 10.1038/s41598-021-87452-z
  • Peer Reviewed / Open Access
• [Journal Article] Conventional type 2 lung dendritic cells are potent inducers of follicular helper T cells in the asthmatic lung (2021)
  • Author(s): Sakurai Shogo、Furuhashi Kazuki、Horiguchi Ryo、Nihashi Fumiya、Yasui Hideki、Karayama Masato、Suzuki Yuzo、Hozumi Hironao、Enomoto Noriyuki、Fujisawa Tomoyuki、Nakamura Yutaro、Inui Naoki、Suda Takafumi
  • Journal Title: Allergology International Volume: 70 Pages: －
  • DOI: 10.1016/j.alit.2021.01.008
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Significance of Interstitial Lung Disease and Its Acute Exacerbation in Microscopic Polyangiitis (2021)
  • Author(s): Hozumi Hironao、Kono Masato、Hasegawa Hirotsugu、Yasui Hideki、Suzuki Yuzo、Karayama Masato、Furuhashi Kazuki、Enomoto Noriyuki、Fujisawa Tomoyuki、Inui Naoki、Nakamura Yutaro、Yokomura Koshi、Nakamura Hidenori、Suda Takafumi
  • Journal Title: Chest Volume: 159 Pages: 2334～2345
  • DOI: 10.1016/j.chest.2021.01.083
  • Peer Reviewed
• [Presentation] Impaired Autophagy Exacerbates Eosinophilic Airway Inflammation in Murine Model of Obesity Asthma (2021)
  • Author(s): Suzuki YUZO
  • Organizer: American Thoracic Society Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] 肺MAC症の予後予測 (2021)
  • Author(s): 鈴木勇三
  • Organizer: 日本結核・非結核性抗酸菌症学会総会・学術講演会
• [Presentation] オートファジー低下はTSLP依存性に肥満喘息を悪化させる (2021)
  • Author(s): 鈴木勇三
  • Organizer: 日本呼吸器学会学術講演会
• [Presentation] 抗線維化薬の切り替えは有益か？ 多施設後方視研究 (2021)
  • Author(s): 鈴木勇三
  • Organizer: 日本呼吸器学会学術講演会