Establishment of imaging biomarkers to evaluate small airway dysfunction for asthma

• Project/Area Number: 18K16152
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Yamaguchi University
• Principal Investigator: Oishi Keiji 山口大学, 医学部附属病院, 診療助教(4日/週) (60771409)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 気管支喘息 / イメージングバイオマーカー / 末梢気道機能障害

Outline of Final Research Achievements

Small airways disease (SAD) may have an important role in asthma. However, imaging biomarkers of the SAD in asthmatics remains to be established. Parametric response mapping (PRM) is a novel radiographic technique, which is a voxel-based imaging technology using inspiratory and expiratory computed tomography (CT) imaging. PRM can quantitatively evaluate the functional SAD (fSAD) in patients with COPD. We evaluated PRMfSAD in asthmatics and examine its correlations with clinical and physiologic variables.
Regardless of the severity of asthma, there are some PRMfSAD lesion. Based on the negative correlation between PRMfSAD and BMI, PRMfSAD and PEF, PRMfSAD may be susceptible to respiratory muscle strength. Based on the positive correlation between PRMfSAD and RV/TLC, PRMfSAD may reflect peripheral airway obstruction. PRM-fSAD was also associated with some Type 2 airway inflammation. Our results suggest that PRM may be useful to evaluate the fSAD in patients with asthma.

Academic Significance and Societal Importance of the Research Achievements

本研究で使用した末梢気道機能障害を評価するイメージングバイオマーカーは、気管支喘息やCOPDなどの閉塞性肺疾患の管理向上に寄与する点で学術的意義がある。また、従来検査では抽出できないような発症早期や軽症時にも病変を検出できる可能性があり、様々な呼吸器疾患や他疾患の早期診断・治療につながるといった波及効果によって医療費の削減にも貢献できる点に社会的意義がある。

Research Products

• [Journal Article] What are key symptoms to be captured for preventing a physician's underestimation of asthma control? (2021)
  • Author(s): Chikumoto Ayumi、Matsunaga Kazuto、Oishi Keiji、Hamada Kazuki、Yamaji Yoshikazu、Hirano Tsunahiko
  • Journal Title: The Journal of Allergy and Clinical Immunology: In Practice Volume: 9 Issue: 1 Pages: 564-566
  • DOI: 10.1016/j.jaip.2020.07.053
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dupilumab: Basic aspects and applications to allergic diseases (2020)
  • Author(s): Matsunaga Kazuto、Katoh Norito、Fujieda Shigeharu、Izuhara Kenji、Oishi Keiji
  • Journal Title: Allergology International Volume: 69 Issue: 2 Pages: 187-196
  • DOI: 10.1016/j.alit.2020.01.002
  • NAID: 130007832970
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease (2020)
  • Author(s): Oishi Keiji、Matsunaga Kazuto、Shirai Toshihiro、Hirai Keita、Gon Yasuhiro
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 8 Pages: 2670-2670
  • DOI: 10.3390/jcm9082670
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Novel Role of Growth Differentiation Factor (GDF)-15 in Overlap with Sedentary Lifestyle and Cognitive Risk in COPD (2020)
  • Author(s): Tsunahiko Hirano, Keiko Doi, Kazuto Matsunaga, Tomoyuki Kakugawa et al.
  • Journal Title: Journal of Clinical Medecine Volume: 9(9) Issue: 9 Pages: 2737-2737
  • DOI: 10.3390/jcm9092737
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytokine Adsorption to Polymyxin B-Immobilized Fiber: An in vitro Study (2020)
  • Author(s): Utsunomiya Toshiaki、Mimura-Kimura Yuka、Yamamoto Takeshi、Aoe Keisuke、Oishi Keiji、Kamei Haruhito、Matsunaga Kazuto、Yano Masafumi、Mimura Yusuke
  • Journal Title: Blood Purification Volume: 50 Issue: 2 Pages: 1-8
  • DOI: 10.1159/000510290
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Comorbid Conditions in Chronic Obstructive Pulmonary Disease: Potential Therapeutic Targets for Unmet Needs (2020)
  • Author(s): Matsunaga Kazuto、Harada Misa、Suizu Junki、Oishi Keiji、Asami-Noyama Maki、Hirano Tsunahiko
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 10 Pages: 3078-3078
  • DOI: 10.3390/jcm9103078
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A New Dyspnea Evaluation System Focusing on Patients’ Perceptions of Dyspnea and Their Living Disabilities: The Linkage between COPD and Frailty (2020)
  • Author(s): Oishi Keiji、Matsunaga Kazuto、Harada Misa、Suizu Junki、Murakawa Keita、Chikumoto Ayumi、Ohteru Yuichi、Matsuda Kazuki、Uehara Sho、Hamada Kazuki、Ohata Shuichiro、Murata Yoriyuki、Yamaji Yoshikazu、Asami-Noyama Maki、Edakuni Nobutaka、Kakugawa Tomoyuki、Hirano Tsunahiko
  • Journal Title: Journal of Clinical Medicine Volume: 9 Issue: 11 Pages: 3580-3580
  • DOI: 10.3390/jcm9113580
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of sinus surgery on type 2 airway and systemic inflammation in asthma (2020)
  • Author(s): Hamada Kazuki、Oishi Keiji、Chikumoto Ayumi、Murakawa Keita、Ohteru Yuichi、Matsuda Kazuki、Uehara Sho、Suetake Ryo、Ohata Shuichiro、Murata Yoriyuki、Yamaji Yoshikazu、Asami-Noyama Maki、Ito Kosuke、Edakuni Nobutaka、Hirano Tsunahiko、Matsunaga Kazuto
  • Journal Title: Journal of Asthma Volume: Epub ahead of print Issue: 6 Pages: 1-9
  • DOI: 10.1080/02770903.2020.1729380
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Detection of type2 biomarkers for response in COPD (2020)
  • Author(s): Yamaji Yoshikazu、Oishi Keiji、Hamada Kazuki、Ohteru Yuichi、Chikumoto Ayumi、Murakawa Keita、Matsuda Kazuki、Suetake Ryo、Murata Yoriyuki、Ito Kosuke、Asami-Noyama Maki、Edakuni Nobutaka、Hirano Tsunahiko、Matsunaga Kazuto
  • Journal Title: Journal of Breath Research Volume: 14 Issue: 2 Pages: 026007-026007
  • DOI: 10.1088/1752-7163/ab71a4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Combination of assist use of short-acting beta-2 agonists inhalation and guidance based on patient-specific restrictions in daily behavior: Impact on physical activity of Japanese patients with chronic obstructive pulmonary disease (2019)
  • Author(s): Hirano Tsunahiko、Matsunaga Kazuto、Hamada Kazuki、Uehara Sho、Suetake Ryo、Yamaji Yoshikazu、Oishi Keiji、Asami Maki、Edakuni Nobutaka、Ogawa Hiromasa、Ichinose Masakazu
  • Journal Title: Respiratory Investigation Volume: 57 Issue: 2 Pages: 133-139
  • DOI: 10.1016/j.resinv.2018.12.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] <p>Time To Revise COPD Treatment Algorithm</p> (2019)
  • Author(s): Matsunaga Kazuto、Oishi Keiji、Miravitlles Marc、Anzueto Antonio
  • Journal Title: International Journal of Chronic Obstructive Pulmonary Disease Volume: Volume 14 Pages: 2229-2234
  • DOI: 10.2147/copd.s219051
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Factors Associated with Physician-Patient Discordance in the Perception of Asthma Control (2019)
  • Author(s): Matsunaga Kazuto、Hamada Kazuki、Oishi Keiji、Yano Masafumi、Yamaji Yoshikazu、Hirano Tsunahiko
  • Journal Title: The Journal of Allergy and Clinical Immunology: In Practice Volume: 7 Issue: 8 Pages: 2634-2641
  • DOI: 10.1016/j.jaip.2019.04.046
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Medication persistence rates and predictive factors for discontinuation of antifibrotic agents in patients with idiopathic pulmonary fibrosis: a real-world observational study (2019)
  • Author(s): Oishi Keiji、Hirano Tsunahiko、Murata Yoriyuki、Hamada Kazuki、Uehara Sho、Suetake Ryo、Yamaji Yoshikazu、Asami-Noyama Maki、Edakuni Nobutaka、Ohata Syuichiro、Utsunomiya Toshiaki、Sakamoto Kenji、Onoda Hideko、Matsumoto Tsuneo、Matsunaga Kazuto、Yano Masafumi
  • Journal Title: Therapeutic Advances in Respiratory Disease Volume: 13
  • DOI: 10.1177/1753466619872890
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Three-step algorithm for biological therapy targeted IgE and IL-5 in severe asthma (2018)
  • Author(s): Oishi Keiji、Matsunaga Kazuto
  • Journal Title: Immunity, Inflammation and Disease Volume: 6 Issue: 3 Pages: 374-376
  • DOI: 10.1002/iid3.233
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characteristics of 2017 GOLD COPD group A: a multicenter cross-sectional CAP study in Japan (2018)
  • Author(s): Oishi Keiji、Hirano Tsunahiko、Hamada Kazuki、Uehara Sho、Suetake Ryo、Yamaji Yoshikazu、Ito Kosuke、Asami-Noyama Maki、Edakuni Nobutaka、Matsunaga Kazuto
  • Journal Title: International Journal of Chronic Obstructive Pulmonary Disease Volume: Volume 13 Pages: 3901-3907
  • DOI: 10.2147/copd.s181938
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] コントロール不良因子とbiological signatureを組み合わせて弁別した重症喘息の臨床特性 (2020)
  • Author(s): 大石景士, 平野綱彦, 水津純輝, 原田美沙, 村川慶多, 大輝祐一, 松田和樹, 上原翔, 濱田和希, 大畑秀一郎, 山路義和, 村田順之, 浅見麻紀, 枝国信貴, 角川智之, 松永和人
  • Organizer: 第1回日本喘息学会学術大会
• [Presentation] 気管支喘息におけるParametric Response Mappingの検討 (2020)
  • Author(s): 大石景士, 平野綱彦, 濱田和希, 椎木健裕, 松田和樹, 末竹諒, 村田順之, 山路義和, 浅見麻紀, 枝国信貴, 松永和人
  • Organizer: 第60回日本呼吸器学会学術講演会
• [Presentation] Biomarker-Based Detection of Type-2 Inflammation in COPD Patients. (2020)
  • Author(s): Oishi K, Hirano T, Chikumoto A, Ohteru Y, Murakawa K, Matsuda K, Hamada K, Suetake R, Yamaji Y, Murata Y, Asami-Noyama M, Edakuni N, Matsunaga K
  • Organizer: ATS 2020
  • Int'l Joint Research
• [Presentation] Characteristics of 2017 GOLD COPD group A: a multicenter cross-sectional CAP study in Japan (2019)
  • Author(s): Keiji Oishi, Tsunahiko Hirano, Kazuki Hamada, Sho Uehara, Ryo Suetake, Yoshikazu Yamaji, Kosuke Ito, Maki Asami-Noyama, Nobutaka Edakuni, Kazuto Matsunaga
  • Organizer: ATS 2019
  • Int'l Joint Research
• [Presentation] The prevalence and clinical characteristics of T2-high and T2-low endtype of severe ubcontrolled asthma distinguished by combining popular type-2 biomarkers (2019)
  • Author(s): Keiji Oishi, Tsunahiko Hirano, Kazuki Matsuda, Kazuki Hamada, Sho Uehara, Ryo Suetake, Yoshikazu Yamaji, Maki Asami-Noyama, Nobutake Edakuni, Kazuto Matsunaga
  • Organizer: ERS 2019
  • Int'l Joint Research
• [Presentation] Imaging biomarkers of the small airways disease in asthmatics (2019)
  • Author(s): Keiji Oishi, Tsunahiko Hirano, Takehiro Shiinoki, Kazuki Hamada, Ayumi Chikumoto, Keita Murakawa, Yuichi Ohteru, Ryo Suetake, Yoriyuki Murata, Yoshikazu Yamaji, Maki Asami-Noyama, Nobutaka Edakuni, Kazuto Matsunaga
  • Organizer: APSR Congress 2019
  • Int'l Joint Research
• [Presentation] Functional small airways disease derived from parametric response mapping in asthma (2019)
  • Author(s): Keiji Oishi, Tsunahiko Hirano, Takehiro Shiinoki, Kazuki Hamada, Ayumi Chikumoto, Keita Murakawa, Yuichi Ohteru, Ryo Suetake, Yoriyuki Murata, Yoshikazu Yamaji, Maki Asami-Noyama, Nobutaka Edakuni, Kazuto Matsunaga
  • Organizer: APSR Congress 2019
  • Int'l Joint Research
• [Presentation] GOLD2017のCOPD重症度判定からみた日本人COPD患者グループAの臨床像 (2019)
  • Author(s): 大石景士，平野綱彦，松永和人，矢野雅文
  • Organizer: 第116回日本内科学会総会・講演会
• [Presentation] タイプ2バイオマーカーを組み合わせて弁別したコントロール不良重症喘息の臨床特性 (2019)
  • Author(s): 大石景士, 平野綱彦, 松田和樹, 濱田和希, 上原翔, 末竹諒, 山路義和, 浅見麻紀, 枝国信貴, 松永和人
  • Organizer: 第59回日本呼吸器学会総会
• [Presentation] The prevalence and clinical characteristics of T2-low and T2-high endotype of severe uncontrolled asthma distinguished by combining type-2 biomarkers (2018)
  • Author(s): Keiji Oishi, Tsunahiko Hirano, Kazuki Matsuda, Kazuki Hamada, Sho Uehara, Ryo Suetake, Yoshikazu Yamaji, Maki Asami-Noyama, Nobutaka Edakuni, Kazuto Matsunaga
  • Organizer: APSR Congress 2018
  • Int'l Joint Research
• [Book] アレルギー診療におけるバイオマーカーの用い方. Modern Physician 38-10 アレルギー診療 総合トレーニング! (2018)
  • Author(s): 大石景士、松永和人
  • Total Pages: 88
  • Publisher: 新興医学出版社