Mycobiota in the airways of allergic bronchopulmonary mycosis

• Project/Area Number: 16K09925
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Tokai University
• Principal Investigator: ASANO Koichiro 東海大学, 医学部, 教授 (60192944)
• Research Collaborator: SHIRAISHI Yoshiki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アレルギー性気管支肺真菌症 / 真菌 / マイクロバイオーム / 好酸球 / アレルギー

Outline of Final Research Achievements

A total of 102 fungal strains isolated from clinical cases with allergic bronchopulmonary mycosis were identified by genetic analysis. In addition to Aspergillus spp., Basidiomycetes and black fungi were detected. We have established a system to evaluate airway mycobiome using PCR amplification of fungus-specific ITS1 region gene and next-generation sequencing.
A. fumigatus has been shown to induce extracellular trap cell death via CD11b and Syk in human eosinophils. Released extracellular traps could be dissolved with DNase.

Academic Significance and Societal Importance of the Research Achievements

アレルギー性気管支肺真菌症の診断において、培養法による真菌の検出は用いられる培地・培養温度・培養期間に大きく影響されることもあり、しかも培養至適条件が真菌によって異なるため気道内に腐生している真菌の全体像を検出できず、信頼性に乏しかった。今回の研究によって気道の真菌叢解析が可能となった。
さらにA. fumigatusにより好酸球のextracellular trap cell deathが直接誘導されることを明らかにし、粘稠な粘液栓が形成される機序の一部が明らかとなると共に、DNaseを用いた治療法の可能性が明らかとなった。

Research Products

• [Journal Article] アレルギー性気管支肺真菌症のバイオマーカー (2019)
  • Author(s): 浅野浩一郎
  • Journal Title: アレルギー・免疫 Volume: 26 Pages: 36-40
• [Journal Article] Eosinophils release extracellular DNA traps in response to Aspergillus fumigatus (2018)
  • Author(s): Muniz Valdirene S.、Silva Juliana C.、Braga Yasmim A.V.、Melo Rossana C.N.、Ueki Shigeharu、Takeda Masahide、Hebisawa Akira、Asano Koichiro、Figueiredo Rodrigo T.、Neves Josiane S.
  • Journal Title: Journal of Allergy & Clinical Immunology Volume: 141 Issue: 2 Pages: 571-585.e7
  • DOI: 10.1016/j.jaci.2017.07.048
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Allergic bronchopulmonary aspergillosis in Japan: A nationwide survey (2018)
  • Author(s): Oguma Tsuyoshi、Taniguchi Masami、Shimoda Terufumi、Kamei Katsuhiko、Matsuse Hiroto、Hebisawa Akira、Takayanagi Noboru、Konno Satoshi、Fukunaga Koichi、Harada Kazuki、Tanaka Jun、Tomomatsu Katsuyoshi、Asano Koichiro
  • Journal Title: Allergology International Volume: 67 Issue: 1 Pages: 79-84
  • DOI: 10.1016/j.alit.2017.04.011
  • NAID: 130006322061
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Allergic bronchopulmonary mycosis ? pathophysiology, histology, diagnosis, and treatment (2018)
  • Author(s): Asano Koichiro、Kamei Katsuhiko、Hebisawa Akira
  • Journal Title: Asia Pacific Allergy Volume: 8 Issue: 3 Pages: e24-e24
  • DOI: 10.5415/apallergy.2018.8.e24
  • Peer Reviewed
• [Journal Article] Allergic Bronchopulmonary Aspergillosis-A Luminal Hypereosinophilic Disease With Extracellular Trap Cell Death. (2018)
  • Author(s): Ueki S, Hebisawa A, Kitani M, Asano K, Neves JS
  • Journal Title: Front Immunol. Volume: 9 Pages: 2346-2346
  • DOI: 10.3389/fimmu.2018.02346
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 真菌関連喘息とその重症化機構 (2018)
  • Author(s): 浅野浩一郎
  • Journal Title: 医学のあゆみ Volume: 255 Pages: 827-831
• [Journal Article] アレルギー性気管支肺真菌症の新知見 (2018)
  • Author(s): 浅野浩一郎
  • Journal Title: 呼吸 eレポート Volume: 2 Pages: 59-66
• [Journal Article] Characteristics of severe asthma with fungal sensitization (2017)
  • Author(s): Masaki Katsunori、Fukunaga Koichi、Asano Koichiro、Betsuyaku Tomoko, et al.
  • Journal Title: Annals of Allergy, Asthma & Immunology Volume: 119 Issue: 3 Pages: 253-257
  • DOI: 10.1016/j.anai.2017.07.008
  • Peer Reviewed
• [Journal Article] Innate immune systems: A clue in the pathogenesis of adult-onset, eosinophilic lung diseases (2017)
  • Author(s): K. Asano
  • Journal Title: Respir Invest Volume: 55 Issue: 2 Pages: 93-93
  • DOI: 10.1016/j.resinv.2017.02.002
  • Open Access / Int'l Joint Research
• [Journal Article] Empyema associated with Campylobacter curvus infection (2017)
  • Author(s): Y. Horio, Y. Shiraishi, N. Watanabe, S. Inoue, T. Imanishi, K. Asano
  • Journal Title: Respirol Case Rep Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Allergic bronchopulmonary aspergillosis in Japan: a nationwide survey (2017)
  • Author(s): T. Oguma, M. Taniguchi, T. Shimoda, K. Kamei, H. Matsuse, A. Hebisawa, N. Takayanagi, S. Konno, K. Fukunaga, K. Harada, J. Tanaka, K. Tomomatsu, K.Asano
  • Journal Title: Allergol Int Volume: 印刷中
  • NAID: 130006322061
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 次世代シーケンサーを用いたアレルギー性気管支肺真菌症の原因真菌解析 (2019)
  • Author(s): 白石 良樹, 小熊 剛, 友松克允, Kryukov Kirill, 中川 草, 今西 規, 蛇澤 晶, 鈴木 純子, 浅野 浩一郎
  • Organizer: 第59回日本呼吸器学会学術講演会
• [Presentation] アレルギー性気管支肺真菌症を正しく診断するために (2019)
  • Author(s): 浅野 浩一郎
  • Organizer: 第59回日本呼吸器学会学術講演会
  • Invited
• [Presentation] Three distinct clinical phenotypes of allergic bronchopulmonary aspergillosis identified by cluster analysis (2018)
  • Author(s): T. Oguma, J. Tanaka, K. Harada, K. Tomomatsu, K. Asano, and Japan ABPM research program
  • Organizer: ATS2018 Annual meeting of American Thoracic Society
  • Int'l Joint Research
• [Presentation] Clinical Diagnostic Criteria for Allergic Bronchopulmonary Mycosis (2018)
  • Author(s): K. Asano, A. Hebisawa, N. Takayanagi, M. Taniguchi, Y. Nakamura, T. Ishiguro, J. Suzuki, J. Tanaka, K. Watai, Y. Fukutomi, T. Oguma, and Japan ABPM research program
  • Organizer: ATS2018 Annual meeting of American Thoracic Society
  • Int'l Joint Research
• [Presentation] アレルギー性気管支炎肺アスペルギルス症の粘液栓への好酸球ETosis の関与 (2018)
  • Author(s): 竹田正秀，植木重治，Neves Josiane，福地峰世，今野泰典，佐藤一洋，佐野正明，廣川 誠，蛇澤 晶，浅野浩一郎
  • Organizer: 第67回日本アレルギー学会学術大会
• [Presentation] Clinical Diagnostic Criteria for Allergic Bronchopulmonary Mycosis (2018)
  • Author(s): Koichiro Asano, Akira Hebisawa, Noboru Takayanagi, Yasuhiko Nakamura, Takashi Ishiguro, Junko Suzuki, Jun Tanaka, Tsuyoshi Oguma
  • Organizer: 8th Advances Against Aspergillosis
  • Int'l Joint Research
• [Presentation] Clinical characteristics of allergic bronchopulmonary mycosis/aspergillosis in Japan (2017)
  • Author(s): Koichiro Asano
  • Organizer: East Asia Allergy Symposium 2017
  • Int'l Joint Research / Invited
• [Presentation] EAACI symposium: Key updates and emerging trends. Asthma-COPD overlap syndrome (2016)
  • Author(s): K. Asano
  • Organizer: Joint congress of Asia Pacific Association of Allergy, Asthma, and Clinical Immunology (APAAACI) and Asia Pacific Association of Pediatric Allergy, Respirology, and Immunology (APAPARI) 2016
  • Place of Presentation: Shangri-La Hotel Kuala Lumpur（クアラルンプール、マレーシア）
  • Year and Date: 2016-10-18
  • Int'l Joint Research / Invited
• [Presentation] Joint ATS/ERS/JRS symposium on severe asthma. Severe Asthma: Lessons Learned from Global Studies (2016)
  • Author(s): K. Asano
  • Organizer: ATS2016 American Thoracic Society International Conference
  • Place of Presentation: Moscone center（サンフランシスコ、米国）
  • Year and Date: 2016-05-15
  • Int'l Joint Research / Invited