Elucidation of the relationship between bacterial colonization in the lower airway and the pathogenesis of severe asthma: a longitudinal and comprehensive study

• Project/Area Number: 19K08649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kindai University (2021); Kyoto University (2019-2020)
• Principal Investigator: MATSUMOTO Hisako 近畿大学, 医学部, 教授 (60359809)
• Co-Investigator(Kenkyū-buntansha): 伊藤 功朗 京都大学, 医学研究科, 准教授 (40447975) ; 小熊 毅 京都大学, 医学研究科, 特定助教 (50601324)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 閉塞性気道疾患 / 下気道細菌叢 / 重症喘息 / SE感作 / 喀痰症状 / microbiome / 混合性炎症 / 黄色ブドウ球菌 / 気流閉塞 / 2型炎症

Outline of Research at the Start

重症喘息の病態に真菌や細菌の下気道への定着が関与する可能性が示されつつある。本研究では、重症喘息例の下気道における細菌・真菌を検索し、微生物定着の有無と血清ペリオスチンを含めた炎症性サイトカイン・メディエーター、真菌や細菌成分への感作、免疫能や内因性ペプチドとの関係を検討する。縦走的、包括的検討により下気道の微生物が喘息の重症化に寄与する機序が明らかになれば、より良い重症喘息の管理につながると考えられる。

Outline of Final Research Achievements

The detection of Staphylococcus aureus in sputum in patients with bronchiectasis, including those with asthma complications, was associated with allergic inflammation and eosinophilic inflammation, potentially via enterotoxin sensitization. On the other hand, the distribution of allergic and eosinophilic inflammation was not identical. In cases of obstructive airway diseases, including severe asthma, high sputum occupancy of γ-Proteobacteria and Haemophilus spp. was associated with not only neutrophilic airway inflammation but also moderate eosinophilic/type 2 airway inflammation (mixed inflammation) and sputum symptoms.

Academic Significance and Societal Importance of the Research Achievements

本研究では重症喘息を含む閉塞性気道疾患例で、喀痰中Proteobacterium綱（G陰性桿菌）の検出は好中球性炎症と関係することが確認されたが、中等度までの好酸球/2型炎症も併存すること、強い好酸球性炎症例ではG陰性桿菌定着が少ないこと、喀痰症状にはG陰性桿菌と好酸球性炎症がともに寄与することを明らかにした。近年重症喘息のみならず、COPDや気管支拡張症でも末梢血好酸球数が管理指標の一つとなってきたが、本研究結果は末梢血好酸球数の解釈も含め、閉塞性気道疾患の長期管理において重要な知見になると考えられる。

Research Products

• [Journal Article] The importance of central airway dilatation in patients with bronchiolitis obliterans (2021)
  • Author(s): Kogo M, Matsumoto H, et al.
  • Journal Title: ERJ Open Res Volume: 25 Issue: 4 Pages: 00123-2021
  • DOI: 10.1183/23120541.00123-2021
  • Peer Reviewed / Open Access
• [Journal Article] Airway clearance ameliorated the control of diffuse panbronchiolitis accompanied by asthma and leukocytoclastic vasculitis (2021)
  • Author(s): Tashima N, Matsumoto H, et al.
  • Journal Title: Allergology International Volume: 70 Issue: 1 Pages: 131-133
  • DOI: 10.1016/j.alit.2020.07.003
  • NAID: 130007966794
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] High serum free IL-18 is associated with decreased omalizumab efficacy: findings from a 2-year omalizumab treatment study (2020)
  • Author(s): Morimoto C, Matsumoto H, et al.
  • Journal Title: J Asthma Volume: 20 Issue: 9 Pages: 1-10
  • DOI: 10.1080/02770903.2020.1766061
  • Peer Reviewed / Open Access
• [Journal Article] Roles of omalizumab in various allergic diseases (2020)
  • Author(s): Okayama Y, Matsumoto H, et al.
  • Journal Title: Allergology International Volume: 69 Issue: 2 Pages: 167-177
  • DOI: 10.1016/j.alit.2020.01.004
  • NAID: 130007832953
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Role of serum periostin in the management of asthma and its comorbidities. (2020)
  • Author(s): Matsumoto H.
  • Journal Title: Respir Investig Volume: 58 Issue: 3 Pages: 144-54
  • DOI: 10.1016/j.resinv.2020.02.003
  • Peer Reviewed
• [Journal Article] Correlation between eosinophil count, its genetic background and body mass index: The Nagahama Study (2020)
  • Author(s): Sunadome H, Matsumoto H, Izuhara Y, Nagasaki T, Kanemitsu Y, Ishiyama Y, Morimoto C, Oguma T, Ito I, Murase K, Muro S, Kawaguchi T, Tabara Y, Chin K, Matsuda F, Hirai T.
  • Journal Title: Allergology International Volume: 69 Issue: 1 Pages: 46-52
  • DOI: 10.1016/j.alit.2019.05.012
  • NAID: 130007788689
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Phenotyping of IgG4-related diseases based on affected organ pattern: A multicenter cohort study using cluster analysis. (2020)
  • Author(s): Niwamoto T, Handa T, Matsui S, Yamamoto H, Yoshifuji H, Abe H, MatsumotoH, Kodama Y, Chiba T, Seno H, Mimori T, Hirai T.
  • Journal Title: Modern Rheumatology Volume: in press Issue: 1 Pages: 235-240
  • DOI: 10.1080/14397595.2019.1703522
  • Peer Reviewed
• [Journal Article] Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ions. (2019)
  • Author(s): Konishi S, Yano T, Tanaka H, Mizuno T, Kanoh H, Tsukita K, Namba T, Tamura A, Yonemura S, Gotoh S, Matsumoto H, Hirai T, Tsukita S.
  • Journal Title: Life Sci Alliance Volume: 2 Issue: 4 Pages: e201900414-e201900414
  • DOI: 10.26508/lsa.201900414
  • NAID: 120007144472
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of self-reported cough intensity and frequency in patients with interstitial lung disease: a cross-sectional study. (2019)
  • Author(s): Sato R, Handa T, Matsumoto H, Kubo T, Hirai T.
  • Journal Title: BMC Pulm Med Volume: 19 Issue: 1 Pages: 247-247
  • DOI: 10.1186/s12890-019-1012-6
  • NAID: 120006773960
  • Peer Reviewed / Open Access
• [Journal Article] Induction of airway remodeling and persistent cough by repeated citric acid exposure in a guinea pig cough model. (2019)
  • Author(s): Cui S, Ito I, Nakaji H, Iwata T, Matsumoto H, Oguma T, Tajiri T, Nagasaki T, Kanemitsu Y, Izuhara H, Mishima M, Niimi A.
  • Journal Title: Respir Physiol Neurobiol. Volume: 263 Pages: 1-8
  • DOI: 10.1016/j.resp.2019.02.002
  • Peer Reviewed / Int'l Joint Research
• [Presentation] COPD・ACO・喘息例における喀痰細菌叢の検討 (2021)
  • Author(s): 森本千絵、松本久子 他
  • Organizer: 第61回日本呼吸器学会学術講演会
• [Presentation] COPD・ACO・喘息例における喀痰細菌叢の検討 (2021)
  • Author(s): 森本千絵、松本久子、他
  • Organizer: 第61回日本呼吸器学会
• [Presentation] Roles of sensitization to Staphylococcus enterotoxin in patients with bronchiectasis (2020)
  • Author(s): Morimoto C, Matsumoto H, et al.
  • Organizer: Eur Respir Society
  • Int'l Joint Research
• [Book] Roles of periostin in asthma. In: Kudo A, editor: Periostin (2019)
  • Author(s): Matsumoto H
  • Total Pages: 5
  • Publisher: Springer