Asthma and COPD overlap: Elucidation of pathophysiology by molecular approach

• Project/Area Number: 26461489
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Yamaguchi University (2015-2016); Wakayama Medical University (2014)
• Principal Investigator: MATSUNAGA Kazuto 山口大学, 医学(系)研究科(研究院), 教授 (20347602)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 気流制限 / 気道可逆性 / 気道炎症 / リモデリング / サイトカイン / ケモカイン / 成長因子 / ガス分子 / 喘息 / COPD / 気流閉塞 / 軌道過敏性

Outline of Final Research Achievements

This study aimed to elucidate the molecular pathology of overlap syndrome of asthma and COPD. Among the inflammation biomarkers assessed, peripheral blood eosinophil count, exhaled NO fraction, exhaled breath condensate IP - 10 increased with asthma and overlap syndrome. It was confirmed that exhaled NO fraction is a useful marker for predicting improvement of airflow limitation and COPD assessment test (CAT) by steroid therapy. It was shown that central expiratory NO and peripheral exhaled NO have equivalent sensitivity and specificity. We also observed that the existence of severe exacerbations and persistently high level of exhaled NO fraction are associated with the rapid progression of airflow limitation in observational studies for asthma.

Research Products

• [Journal Article] Persistently high exhaled nitric oxide and loss of lung function in controlled asthma (2016)
  • Author(s): Kazuto Matsunaga Tsunahiko Hirano Asako Oka kousuke Ito Nobutaka Edakuni
  • Journal Title: Allergology International Volume: 65 Issue: 3 Pages: 266-271
  • DOI: 10.1016/j.alit.2015.12.006
  • NAID: 130005165877
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] Differences in physical activity according to mMRC grade in patients with COPD. (2016)
  • Author(s): Hayata A, Minakata Y, Matsunaga K, Nakanishi M, Yamamoto N
  • Journal Title: International Journal of COPD Volume: 11 Pages: 2203-2208
  • Peer Reviewed
• [Journal Article] Stratifying the risk of COPD exacerbati on using the modified Medical Research Council scale: A multicenter cross-sectional CAP study. (2015)
  • Author(s): Matsunaga, K, A. Hayata, K. Akamatsu, T. Hirano, T. Tamada, T. Kamei, T. Tsuda, H. Nakamura, T. Takahashi, S. Hozawa, Y. Mori, Y. Sakamoto, K. Kimura, U. Katsumata, M. Miura, M. Ichinose.
  • Journal Title: Respiratory Investigation Volume: 53 Issue: 2 Pages: 82-85
  • DOI: 10.1016/j.resinv.2014.10.006
  • Peer Reviewed / Open Access
• [Journal Article] Progression of Irreversible Airflow Limitation in Asthma: Correlation with Severe Exacerbations (2015)
  • Author(s): Matsunaga K, Hirano T, Oka A, Tanaka A, Kanai K, Kikuchi T, Hayata A, Akamatsu H, Akamatsu K, Koh Y, Nakanishi M, Minakata Y, Yamamoto N
  • Journal Title: J Allergy Clin Immunol Pract Volume: 3 Issue: 5 Pages: 759-764
  • DOI: 10.1016/j.jaip.2015.05.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Response to Systemic Corticosteroids on Persistently High Exhaled Nitric Oxide in Severe Asthma. (2015)
  • Author(s): Hirano T, Ito K, Edakuni N, Matsunaga K
  • Journal Title: J Allergy Ther Volume: 6 Issue: 04 Pages: 2-4
  • DOI: 10.4172/2155-6121.1000219
  • Peer Reviewed / Open Access
• [Journal Article] Cigarette smoke augments MUC5AC production via the TLR3-EGFR pathway in airway epithelial cells. (2015)
  • Author(s): K. Kanai, A. Koarai, Y.Shishikura, H. Sugiura, T. Ichikawa, T. Kikuchi, K. Akamatsu, T. Hirano, M. Nakanishi, K. Matsunaga, Y. Minakata and M.Ichinose.
  • Journal Title: Respir Investig. Volume: in press Issue: 4 Pages: 137-148
  • DOI: 10.1016/j.resinv.2015.01.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of pharmacologic treatment based on airflow limitation and breathlessness on daily physical activity in patients with chronic obstructive pulmonary disease (2015)
  • Author(s): Minakata Y, Morishita Y, Ichikawa T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Ichinose M
  • Journal Title: Int J Chron Obstruct Pulmon Dis Volume: 10 Pages: 1275-1282
  • DOI: 10.2147/copd.s84134
  • Peer Reviewed / Open Access
• [Journal Article] Biomarker-based detection of ACOS in COPD populations. (2015)
  • Author(s): Tamada, T., H. Sugiura, T. Takahashi, K. Matsunaga, K. Kimura, U. Katsumata, D. Takekoshi, T. Kikuchi, K. Ohta and M. Ichinose.
  • Journal Title: Int J Chron Obstruct Pulmon Di Volume: 10 Pages: 2169-2176
  • DOI: 10.2147/copd.s88274
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] チオトロピウム(喘息に対する適応拡大) (2015)
  • Author(s): 早田敦志, 松永和人
  • Journal Title: 分子呼吸器病 Volume: 19 Pages: 83-85
• [Journal Article] 呼気中一酸化窒素、一酸化炭素の有用性と課題 (2015)
  • Author(s): 平野綱彦, 松永和人
  • Journal Title: アレルギー･免疫 Volume: 22 Pages: 30-39
• [Journal Article] 喘息の疫学：特に高齢者喘息における現状と問題点 (2015)
  • Author(s): 松永和人
  • Journal Title: PROGRESS IN MEDICINE Volume: 35 Pages: 1533-1539
• [Journal Article] 呼吸機能検査 (2015)
  • Author(s): 平野綱彦, 松永和人
  • Journal Title: アレルギーの臨床 Volume: 35 Pages: 27-30
• [Journal Article] 難治性喘息におけるTNF-LIGHTの意義 (2015)
  • Author(s): 平野綱彦, 松永和人
  • Journal Title: アレルギーの臨床 Volume: 35 Pages: 42-43
• [Journal Article] Ongoing Allergic Rhinitis Impairs Asthma Control by Enhancing the Lower Airway Inflammation (2014)
  • Author(s): Oka A, Matsunaga K, Kamei T, Sakamoto Y, Hirano T, Hayata A, Akamatsu K, Kikuchi T, Hiramatsu M, Ichikawa T, Nakanishi M, Minakata Y, Yamamoto N
  • Journal Title: J Allergy Clin Immunol Pract Volume: 2 Issue: 2 Pages: 172-178
  • DOI: 10.1016/j.jaip.2013.09.018
  • Peer Reviewed
• [Journal Article] TLR3 activation augments matrix metalloproteinase production through reactive nitrogen species generation in human lung fibroblasts. (2014)
  • Author(s): Ichikawa T, Sugiura H, Koarai A, Minakata Y, Kikuchi T, Morishita Y, Oka A, Kanai K, Kawabata H, Hiramatsu M, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Yamamoto N, Ichinose M.
  • Journal Title: J Immunol Volume: 192 Issue: 11 Pages: 4977-4988
  • DOI: 10.4049/jimmunol.1302919
  • Peer Reviewed
• [Journal Article] Changes in forced expiratory volume in 1 second over time in patients with controlled asthma at baseline (2014)
  • Author(s): Kazuto Matsunaga
  • Journal Title: Respiratory Medicine Volume: 108 Issue: 7 Pages: 976-982
  • DOI: 10.1016/j.rmed.2014.04.014
  • Peer Reviewed
• [Journal Article] Feasibility of Flying Disc Game for Patients with Oxygen Therapy. (2014)
  • Author(s): 4.Honda Y, Minakata Y, Morishita Y, Sugino A, Hayata A, Ichikawa T, Nakanishi M, Matsunaga K, Yamamoto N
  • Journal Title: Clin Rse Pulmonol Volume: 2 Pages: 1024-1024
  • Peer Reviewed / Open Access
• [Journal Article] ステロイド薬使用に伴う副作用とその対策 (2014)
  • Author(s): 佐野綾香, 平野綱彦, 松永和人
  • Journal Title: 呼吸 Volume: 33 Pages: 360-364
• [Journal Article] 気道過敏性検査 (2014)
  • Author(s): 松永和人
  • Journal Title: Repiratory Medical Research Volume: 2 Pages: 51-54
• [Journal Article] 鼻炎合併喘息におけるコントロール不良の規定因子 (2014)
  • Author(s): 松永和人
  • Journal Title: アレルギーの臨床 Volume: 34 Pages: 85-88
• [Journal Article] 喘息発作時のテオフィリン薬使用の是非について Conの立場から (2014)
  • Author(s): 早田敦志 松永和人
  • Journal Title: 喘息 Volume: 27 Pages: 95-98
• [Journal Article] 気道閉塞の変動性とその臨床評価 (2014)
  • Author(s): 早田敦志 松永和人
  • Journal Title: アレルギー・免疫 Volume: 21 Pages: 23-30
• [Presentation] FeNOと抗炎症治療 (2016)
  • Author(s): 松永和人
  • Organizer: 第26回国際喘息学会日本・北アジア部会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2016-09-17
  • Int'l Joint Research / Invited
• [Presentation] Survival from acute exacerbation of idiopathic pulmonary fibrosis with or without direct hemoperfusion with polymyxin B-immobilized fiber column:A retrospective analysis. (2016)
  • Author(s): Keiji Oishi, Keisuke Aoe, Yusuke Mimura, Yoriyuki Murata, Kenji Sakamoto, Wataru Koutoku, Tsuneo Matsumoto, Hiroshi Ueoka, Kazuto Mastunaga, Masafumi Yano.
  • Organizer: ERS INTERNATIONAL CONGRESS 2016
  • Place of Presentation: LONDON（United Kingdom）
  • Year and Date: 2016-09-05
  • Int'l Joint Research
• [Presentation] Cross-talk between TNF-LIGHT and nitrosative stress in the airway remodeling of asthma. (2016)
  • Author(s): Tsunahiko Hirano, Kosuke Ito, Nobutaka Edakuni, Kazuto Matsunaga
  • Organizer: ERS INTERNATIONAL CONGRESS 2016
  • Place of Presentation: LONDON（United Kingdom）
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Presentation] One airway one diseaseと炎症性メディエーター：脂質メディエーターを中心に (2016)
  • Author(s): 松永和人
  • Organizer: 第65回日本アレルギー学会学術大会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2016-06-18
  • Invited
• [Presentation] Enhancement to asthma management efficiency by FeNO measurement. (2016)
  • Author(s): Kazuto Matsunaga
  • Organizer: The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
  • Place of Presentation: SENDAI INTERNATIONAL CENTER（宮城県仙台市）
  • Year and Date: 2016-05-22
  • Int'l Joint Research / Invited
• [Presentation] 呼気NOによる喘息モニタリングの意義 (2016)
  • Author(s): 松永和人
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-10
  • Invited
• [Presentation] 喘息気道のリモデリング進展は防止できるか？ (2016)
  • Author(s): 松永和人
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-09
  • Invited
• [Presentation] 病像・病態からみた高齢者喘息 (2016)
  • Author(s): 松永和人
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-08
  • Invited
• [Presentation] COPD:個別化治療の重要性 (2015)
  • Author(s): 松永和人
  • Organizer: 第54回日本呼吸器学会中国・四国地方会
  • Place of Presentation: くにびきメッセ（島根県松江市）
  • Year and Date: 2015-12-19
  • Invited
• [Presentation] 呼気NO/EBC (2015)
  • Author(s): 松永和人
  • Organizer: 日本アレルギー学会 第2回総合アレルギー講習会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-12-13
  • Invited
• [Presentation] COPDにおける気道炎症評価の意義 (2015)
  • Author(s): 松永和人
  • Organizer: 第75回日本呼吸器学会・日本結核病学会・日本サルコイドーシス／肉芽腫性疾患学会 九州支部 秋季学術講演会
  • Place of Presentation: ホテルグランデはがくれ（佐賀県佐賀市）
  • Year and Date: 2015-10-02
  • Invited
• [Presentation] Clinical Application of Exhaled NO Measurements in COPD. (2015)
  • Author(s): Matsunaga K
  • Organizer: The 25th Congress of Interasma Japan/North Asia
  • Place of Presentation: ホテルニューグランド（神奈川県横浜市）
  • Year and Date: 2015-09-04
  • Int'l Joint Research / Invited
• [Presentation] 高齢進行期胸部悪性腫瘍患者においてGFR値を予測する新たな推算式の検討 (2015)
  • Author(s): 菊池崇史, 赤松弘朗, 盛啓太, 金井一修, 赤松啓一郎, 洪泰浩, 中西正典, 松永和人, 上田弘樹, 山本信之
  • Organizer: 第13回日本臨床腫瘍学会学術集会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2015-07-16
• [Presentation] 喘息治療の進歩と今後の課題 (2015)
  • Author(s): 松永和人
  • Organizer: 第115回日本結核病学会近畿地方会 第85回日本呼吸器学会近畿地方会
  • Place of Presentation: 奈良県文化会館（奈良県奈良市）
  • Year and Date: 2015-07-11
  • Invited
• [Presentation] VBNとEBUS-GSによって診断し得たクリプトコッカス症の二例 (2015)
  • Author(s): 岡亜早子, 田中彩加, 金井一修, 菊池崇史, 早田敦志, 赤松弘朗, 市川朋宏, 赤松啓一郎, 洪泰浩, 中西正典, 松永和人, 平野綱彦, 中村靖司, 山本信之
  • Organizer: 第38回日本呼吸器内視鏡学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-06-12
• [Presentation] PERSISTENTLY HIGH EXHALED NITRIC OXIDE AND LUNG FUNCTION DECLINE IN PATIENTS WITH CONTROLLED ASTHMA AT BASELINE. (2015)
  • Author(s): Matusnaga K
  • Organizer: The 64th Meeting of Japanese Society of Allergology
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2015-05-28
• [Presentation] Statifying the risk of COPD exacerbation using the modified Medical Research Council scale: a multicenter cross-sectional CAP study. (2015)
  • Author(s): Matsunaga K, Oka A, Hayata A, Akamtsu K, Hirano T, Ichinose M
  • Organizer: 2015 ATS International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-19
  • Int'l Joint Research
• [Presentation] Effect of Inhaled Short-Acting Bate-2 Agonist (Procaterol) on Physical Activity of Patients with Chronic Obstructive Pulmonary disease. (2015)
  • Author(s): Hirano T, Matsunaga K, Ogawa H, Minakata Y, Akamatsu K, Nakanishi M, Ichikawa T, Ichinose M
  • Organizer: 2015 ATS International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2015-05-18
  • Int'l Joint Research
• [Presentation] Establishment of multiplexed ultra-sensitive detection of epidermal growth factor receptor mutations using picodroplet digital PCR. (2015)
  • Author(s): Akamatsu H, Koh Y, Watanabe M, Kikuchi T, Nakanishi M, Matsunaga K, Yamamoto N
  • Organizer: American Association for Cancer Research Annual Meeting 2015
  • Place of Presentation: Philadelphia, Pennsylvania, USA
  • Year and Date: 2015-04-22
  • Int'l Joint Research
• [Presentation] 呼気NO測定 (2015)
  • Author(s): 松永和人
  • Organizer: 第55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（東京都千代田区）
  • Year and Date: 2015-04-17
  • Invited
• [Presentation] 当院気管支鏡検査における迅速細胞診(Rapid on-site evaluation ; ROSE)の検討 (2015)
  • Author(s): 金井一修, 赤松弘朗, 松本安子, 田中彩加, 菊池崇史, 洪泰浩, 中西正典, 松永和人, 平野綱彦, 山本信之
  • Organizer: 第112回日本内科学会講演会
  • Place of Presentation: みやこめっせ（京都府左京区）
  • Year and Date: 2015-04-11
• [Presentation] ASSOCIATION OF SEVERE EXACERBATION WITH FEV1 DECLINE AND LOSS OF AIRWAY REVERSIBILITY ASTHMA (2014)
  • Author(s): Matsunaga K, Ichikawa T, Akamatsu K, Hirano T
  • Organizer: 2014 ERS International Congress
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] PERSISTENTLY HIGH EXHALED NITRIC OXIDE AND LUNG FUNCTION DECLINE IN PATIENTS WITH CONTROLLED ASTHMA AT BASELINE (2014)
  • Author(s): Matsunaga K, Ichikawa T, Akamatsu K, Hirano T
  • Organizer: 2014 ERS International Congress
  • Place of Presentation: Munich, Germany
  • Year and Date: 2014-09-06 – 2014-09-10
• [Presentation] Cigarette smoke augments MUC5AC mucin production via TLR3-EGFR pathway in airway epithelial cells (2014)
  • Author(s): Kanai K, Koarai A, Sugiura H, Ichikawa T, Kikuchi T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, and Ichinose M
  • Organizer: 2014 ATS International Conference
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-05-22
• [Presentation] 高齢者喘息の診断と治療: アップデート (2014)
  • Author(s): 松永和人
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都
  • Year and Date: 2014-05-09 – 2014-05-11
  • Invited
• [Presentation] 長期管理中の喘息患者における気道閉塞の進展：重症増悪の影響 (2014)
  • Author(s): 松永和人, 岡亜早子, 市川朋宏, 平野綱彦, 赤松啓一郎, 中西正典
  • Organizer: 第26回日本アレルギー学会春季臨床大会
  • Place of Presentation: 京都
  • Year and Date: 2014-05-09 – 2014-05-11
• [Presentation] Changes in forced expiratiry volume in 1 second over time in patients with controlled asthma at baseline. (2014)
  • Author(s): Matsunaga K, Ichikawa T, Oka A, Morishita Y, Kanai K, Hiramatsu M, Akamatsu H, Kawabata H, Kikuchi T, Akamatsu K, Hirano T, Koh Y, Nakanishi M, Minakata Y, Yamamoto N
  • Organizer: The 54th Annual Meeting of The Japanese Respiratory Society
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2014-04-27
• [Book] 喘息・COPD・ACOSの鑑別はどう進める？ もう悩まない！喘息・COPD・ACOSの外来診療 (2016)
  • Author(s): 松永和人
  • Total Pages: 205
  • Publisher: 羊土社
• [Book] COPD・ACOS関連疾患. もう悩まない！喘息・COPD・ACOSの外来診療 (2016)
  • Author(s): 松永和人
  • Total Pages: 205
  • Publisher: 羊土社
• [Book] COPD(慢性閉塞性肺疾患). 今日の診療のためにガイドライン外来診療2016 (2016)
  • Author(s): 大石景士, 松永和人
  • Total Pages: 605
  • Publisher: 日経メディカル開発
• [Book] 喘息：呼気NO測定の活用法. 内科INTERNAL 12 (2016)
  • Author(s): 大石景士, 松永和人
  • Total Pages: 1181
  • Publisher: 南江堂
• [Book] 呼気検査. アレルギーの疾患のすべて (2016)
  • Author(s): 松永和人
  • Total Pages: 366
  • Publisher: 日本医師会雑誌
• [Book] 新しい検査：呼気一酸化窒素測定、呼吸器疾患診療の最先端 (2015)
  • Author(s): 松永和人
  • Total Pages: 502
  • Publisher: 先端医療技術研究所
• [Book] 薬物によるコントロール・段階的薬剤投与プラン 喘息予防・管理ガイドライン2015 (2015)
  • Author(s): 松永和人
  • Total Pages: 317
  • Publisher: 協和企画
• [Book] Oxidative stress and respiratory muscle dysfunction. Studies on Respiratory Disorders. (2014)
  • Author(s): Matsunaga K, Minakata Y
  • Total Pages: 394
  • Publisher: Humana Press
• [Book] 呼気NO. 呼吸機能検査テキスト 原理、測定法の実際から臨床例まで (2014)
  • Author(s): 松永和人
  • Total Pages: 88
  • Publisher: 呼吸研究
• [Book] 気管支喘息. 呼吸機能検査テキスト 原理、測定法の実際から臨床例まで (2014)
  • Author(s): 松永和人
  • Total Pages: 88
  • Publisher: 呼吸研究