Understanding of pathogenesis of severe asthma and its exacerbation through geno-endo-phenotyping

• Project/Area Number: 16K09535
• 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: Kyoto University
• Principal Investigator: Matsumoto Hisako 京都大学, 医学研究科, 准教授 (60359809)
• Co-Investigator(Kenkyū-buntansha): 長崎 忠雄 京都大学, 医学研究科, 医員 (40747862) ; 小熊 毅 京都大学, 医学研究科, 特定助教 (50601324)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: IL-18 / ORMDL3 / 血清IL-18 / inflammasome / 肥満 / アレルギー・喘息 / ゲノム / IL4RA / periostin

Outline of Final Research Achievements

This study showed that specific combination of gene polymorphisms of IL4RA and POSTN was associated with low serum periostin levels. When a specific genotype of ORMDL3 was added to this combination, risks of asthma exacerbation were increased. These associations may reflect the presence of geno-endo-phenotype of non-type 2 inflammation with asthma exacerbations.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から、非2型炎症を呈しながら喘息増悪リスクを有する可能性のある遺伝子多型の組み合わせが確認され、一定のgeno-endo-phenotypeが示された。組み合わせに入った遺伝子の一つは、ライノウイルス感染への感受性に関わる可能性のある遺伝子であり、何らかのウイルス感染との関係が示唆される。本結果は非2型炎症型喘息の病態解明の端緒になり、有意義な結果が得られたと考えられる。

Research Products

• [Journal Article] Independent Factors Contributing to Daytime and Nighttime Asthmatic Cough Refractory to Inhaled Corticosteroids. (2019)
  • Author(s): Kanemitsu Y, Matsumoto H, Oguma T, Nagasaki T, Ito I, Izuhara Y, Tajiri T, Iwata T, Mishima M, Niimi A.
  • Journal Title: J Investig Allergol Clin Immunol. Volume: 29 Issue: 1 Pages: 30-39
  • DOI: 10.18176/jiaci.0281
  • Peer Reviewed / Open Access
• [Journal Article] Our obligation to find treatable and untreatable traits in patients with chronic airway diseases. (2019)
  • Author(s): Matsumoto H
  • Journal Title: Respir Investig Volume: Epub Issue: 4 Pages: 293-294
  • DOI: 10.1016/j.resinv.2019.03.003
  • Peer Reviewed
• [Journal Article] Roles of Periostin in Asthma. (2019)
  • Author(s): Matsumoto H
  • Journal Title: Adv Exp Med Biol. Volume: 1132 Pages: 145-159
  • DOI: 10.1007/978-981-13-6657-4_15
  • ISBN: 9789811366567, 9789811366574
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The prevalence and disease burden of severe eosinophilic asthma in Japan. (2019)
  • Author(s): Nagasaki T, Sato K, Kume N, Matsumoto H. et al.
  • Journal Title: J Asthma Volume: Epub Issue: 11 Pages: 1147-1158
  • DOI: 10.1080/02770903.2018.1534967
  • Peer Reviewed
• [Journal Article] Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab. (2018)
  • Author(s): Suzukawa M, Matsumoto H, et al.
  • Journal Title: Respir Med Volume: 134 Pages: 95-102
  • DOI: 10.1016/j.rmed.2017.12.002
  • Peer Reviewed
• [Journal Article] IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype (2017)
  • Author(s): Sunadome H.、Matsumoto H.、et al.
  • Journal Title: Clinical & Experimental Allergy Volume: 47 Issue: 8 Pages: 998-1006
  • DOI: 10.1111/cea.12927
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The usefulness of monomeric periostin as a biomarker for idiopathic pulmonary fibrosis (2017)
  • Author(s): Ohta S, Okamoto M, Fujimoto K, Sakamoto N, Takahashi K, Yamamoto H, Kushima H, Ishii H, Akasaka K, Ono J, Kamei A, Azuma Y, Matsumoto H, Yamaguchi Y, Aihara M, Johkoh T, Kawaguchi A, Ichiki M, Sagara H, Kadota JI, Hanaoka M, Hayashi SI, Kohno S, Hoshino T, Izuhara K
  • Journal Title: PloS one Volume: 12 Issue: 3 Pages: e0174547-e0174547
  • DOI: 10.1371/journal.pone.0174547
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Xolair導入後の血清総IgEなどの推移 (2018)
  • Author(s): 森本千絵、松本久子、ほか
  • Organizer: 第67回日本アレルギー学会学術大会
• [Presentation] 血清ペリオスチン低値喘息群における増悪因子 (2017)
  • Author(s): 石山祐美、松本久子、他
  • Organizer: 第57回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム