Chronic infection and immune response in COPD patients

• Project/Area Number: 21590964
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyoto University
• Principal Investigator: MURO Shigeo 京都大学, 医学研究科, 講師 (60344454)
• Co-Investigator(Kenkyū-buntansha): ITO Isao 京都大学, 医学研究科, 助教 (40447959) ; NARUISHI Koji 岩手医科大学, 歯学部, 准教授 (00346446) ; SATO Susumu 京都大学, 医学研究科, 助教 (40378691) ; 伊藤 功朗 京都大学, 医学研究科, 助教 (40447975) ; 黄瀬 大輔 京都大学, 医学研究科, 医員 (50572418) ; 星野 勇馬 京都大学, 医学研究科, 助教 (00378746) ; 小川 恵美子 滋賀医科大学, 保健管理センター, 講師 (00378671)
• Co-Investigator(Renkei-kenkyūsha): TAKASHIBA Shogo 岡山大学, 歯学部, 教授 (50226768) ; MISHIMA Michiaki 京都大学, 医学研究科, 教授 (60190625)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: COPD増悪 / 慢性感染 / 宿主免疫 / 感染 / 慢性閉塞性肺疾患 / 気道炎症 / 歯周病 / MAPK

Research Abstract

Our prospective observational study including 93 COPD patients showed that the numbers of exacerbations and the rate of individuals with frequent exacerbations(at least two per year) were significantly lower in patients with higher IgG titer than those with normal IgG titer. Thus in contrast to our hypothesis, normal-IgG titer for periodontitis-related antibody can be an independent predictor of frequent exacerbations suggesting that humoral immune response associates with COPD exacerbations. We also found that COPD exacerbation accelerated the emphysema progression in spite of current additional therapy during exacerbations.

Research Products

• [Journal Article] Emphysema distribution and annual changes in pulmonary function in male patients with chronic obstructive pulmonary disease (2012)
  • Author(s): Tanabe N, Muro S, Tanaka S, Sato S, Oguma T, Kiyokawa H, Takahashi T, Kinose D, Hoshino Y, Kubo T, Ogawa E, Hirai T, Mishima M. Respir Res
  • Journal Title: Epub ahead of print Volume: 13(1) Issue: 1 Pages: 31-31
  • DOI: 10.1186/1465-9921-13-31
  • Peer Reviewed
• [Journal Article] Computed tomography assessment of pharmacological lung volume reduction induced by bronchodilators in COPD (2012)
  • Author(s): Tanabe N, Muro S, Oguma T, Sato S, Kiyokawa H, Takahashi T, Kudo M, Kinose D, Kubo T, Hoshino Y, Ogawa E, Hirai T, Mishima M. COPD
  • Journal Title: COPD Volume: 9 Issue: 4 Pages: 1-8
  • DOI: 10.3109/15412555.2012.674986
  • Peer Reviewed
• [Journal Article] Oxidative stress induced Interleukin-32 mRNA expression in human bronchial epithelial cells (2012)
  • Author(s): Kudo M, Ogawa E, Kinose D, Haruna A, Takahashi T, Tanabe N, Marumo S, Hoshino Y, Hirai T, Sakai H, Muro S, Date H, Mishima M
  • Journal Title: Respir Res Volume: 13 Issue: 1 Pages: 19-19
  • DOI: 10.1186/1465-9921-13-19
  • Peer Reviewed
• [Journal Article] Impact of COPD Exacerbations on Osteoporosis Assessed by Chest CT Scan (2012)
  • Author(s): Kiyokawa H, Muro S, Oguma T, Sato S, Tanabe N, Takahashi T, Kudo M, Kinose D, Kondoh H, Kubo T, Hoshino Y, Ogawa E, Hirai T, Mishima M
  • Journal Title: Epub Volume: 9(3) Issue: 3 Pages: 235-42
  • DOI: 10.3109/15412555.2011.650243
  • NAID: 120004873856
  • Peer Reviewed
• [Journal Article] A NOD2 gene polymorphism is associated with the prevalence and severity of chronic obstructive pulmonary disease in a Japanese population (2012)
  • Author(s): Kinose D, Ogawa E, Hirota T, Ito I, Kudo M, Haruna A, Marumo S, Hoshino Y, Muro S, Hirai T, Sakai H, Date H, Tamari M, Mishima M
  • Journal Title: Respirology Volume: 17(1) Issue: 1 Pages: 164-71
  • DOI: 10.1111/j.1440-1843.2011.02069.x
  • Peer Reviewed
• [Journal Article] Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease (2011)
  • Author(s): Tanabe N, Muro S, Hirai T, Oguma T, Terada K, Marumo S, Kinose D, Ogawa E, Hoshino Y, Mishima M
  • Journal Title: Am J Respir Crit Care Med Volume: 183(12) Issue: 12 Pages: 1653-9
  • DOI: 10.1164/rccm.201009-1535oc
  • Peer Reviewed
• [Journal Article] Impact of exacerbations on emphysema progression in chronic obstructive pulmonary disease (2011)
  • Author(s): Tanabe N, Muro S, et.al
  • Journal Title: Am J Respir Crit Care Med Volume: 15 Issue: 12 Pages: 1653-9
  • DOI: 10.1164/rccm.201104-0615ed
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide induced connective tissue growth factor gene expression in human bronchial epithelial cells (2010)
  • Author(s): Nishioka M, Ogawa E, Kinose D, Haruna A, Ohara T, Ito I, Hoshino Y, Ito Y, Matsumoto H, Niimi A, Mio T, Chin K, Hirai T, Muro S, Mishima M
  • Journal Title: Respirology Volume: 15(4) Pages: 669-76
  • Peer Reviewed
• [Journal Article] CT scan findings of emphysema predict mortality in COPD (2010)
  • Author(s): Haruna A, Muro S, Nakano Y, Ohara T, Hoshino Y, Ogawa E, Hirai T, Niimi A, Nishimura K, Chin K, Mishima M
  • Journal Title: Chest Volume: 138(3) Issue: 3 Pages: 635-40
  • DOI: 10.1378/chest.09-2836
  • Peer Reviewed
• [Journal Article] Relationship between peripheral airway function and patient-reported outcomes in COPD : a cross-sectional study (2010)
  • Author(s): Haruna A, Oga T, Muro S, Ohara T, Sato S, Marumo S, Kinose D, Terada K, Nishioka M, Ogawa E, Hoshino Y, Hirai T, Chin K, Mishima M
  • Journal Title: BMC Pulm Med Volume: 10 Issue: 1 Pages: 10-10
  • DOI: 10.1186/1471-2466-10-10
  • NAID: 120004754366
  • Peer Reviewed
• [Journal Article] Abnormal swallowing reflex and COPD exacerbations (2010)
  • Author(s): Terada K, Muro S, Ohara T, Kudo M, Ogawa E, Hoshino Y, Hirai T, Niimi A, Chin K, Mishima M
  • Journal Title: Chest Volume: 137(2) Issue: 2 Pages: 326-32
  • DOI: 10.1378/chest.09-0482
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide induced connective tissue growth factor gene expression in human bronchial epithelial cells. (2010)
  • Author(s): 西岡慶喜、小川恵美子、室繁郎
  • Journal Title: Respirology Volume: 15(4) Pages: 134-138
  • Peer Reviewed
• [Journal Article] CT scan findings of emphysema predict mortality in COPD. (2010)
  • Author(s): 春名茜、室繁郎
  • Journal Title: Chest Volume: 138(3) Pages: 635-640
  • Peer Reviewed
• [Journal Article] Relationship between peripheral airway function and patient-reported outcomes in COPD (2010)
  • Author(s): Haruna A, Muro S, et al
  • Journal Title: BMC Pulm Med 10 Pages: 1-10
  • Peer Reviewed
• [Journal Article] Cough-reflex sensitivity to inhaled capsaicin in COPD associated with increased exacerbation frequency (2009)
  • Author(s): Terada K, Muro S, Ohara T, Haruna A, Marumo S, Kudo M, Ogawa E, Hoshino Y, Hirai T, Niimi A, Mishima M
  • Journal Title: Respirology Volume: 14(8) Issue: 8 Pages: 1151-5
  • DOI: 10.1111/j.1440-1843.2009.01620.x
  • Peer Reviewed
• [Journal Article] Abnormal awallowing reflex and COPD exacerbations. (2009)
  • Author(s): Terada K, Muro S, et. al.
  • Journal Title: Chest 137 Pages: 326-332
  • Peer Reviewed
• [Journal Article] CT emphysema predicts mortality in COPD
  • Author(s): Haruna A, Muro S, et al
  • Journal Title: Chest (In press)
  • Peer Reviewed
• [Presentation] Annual Changes Of "Lung Age". Validation Of Lung Age Equation By 5-Year Follow Up Study In Japan (2012)
  • Author(s): S. Sato, S. Muro, T. Takahashi, T. Hirai, M. Mishima, A. Sato
  • Organizer: American Thoracic Society Poster Session
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2012-05-23
• [Presentation] Correlation of Vascular Endothelial Growth Factor Receptor 2 With Pulmonary Function And Emphysematous Change In Early Chronic Obstructive Pulmonary Disease (2012)
  • Author(s): T. Takahashi, E. Ogawa, A. Haruna, M. Kudo, H. Kiyokawa, N. Tanabe, D. Kinose, S. Sato, Y. Hoshino, T. Hirai, H. Sakai, Y. Nakano, S. Muro, M. Mishima
  • Organizer: American Thoracic Society Poster Session
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2012-05-22
• [Presentation] Impact of COPD Exacerbations On Osteoporosis Assessed By Chest CT Scan (2012)
  • Author(s): H. Kiyokawa, S. Muro, T. Oguma, S. Sato, N. Tanabe, T. Takahashi, M. Kudo, D. Kinose, Y. Hoshino, E. Ogawa, T. Hirai, M. Mishima
  • Organizer: American Thoracic Society Poster Discussion Session
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2012-05-22
• [Presentation] Increased TLR3 Gene Expression In Epithelial Cells Of COPD Patients/D. Kinose (2012)
  • Author(s): E. Ogawa, S. Muro, W. M. Elliott, J. C. Hogg, M. Mishima
  • Organizer: American Thoracic Society Thematic Poster Session
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2012-05-20
• [Presentation] Comorbidities of chronic obstructive pulmonary disease (2012)
  • Author(s): 室繁郎
  • Organizer: 第52回日本呼吸器学会
  • Year and Date: 2012-04-22
• [Presentation] シンポジウム「COPDの臨床的諸問題」 (2011)
  • Author(s): 室繁郎
  • Organizer: 第51回日本呼吸器学会
  • Year and Date: 2011-04-23
• [Presentation] Long Term Effect Of Tiotropium On Airway Dimension Assessed By Computed Tomography In COPD Patients (2011)
  • Organizer: American Thoracic Society
• [Presentation] Effects of thioredoxin-1 on accelerated emphysema progression in cigarette smoke-exposed mice challenged with polyinosine-polycytidylic acid (2010)
  • Author(s): N. Tanabe, Y. Hoshino, H. Kiyokawa, S. Marumo, E. Ogawa, S. Muro, T. Hirai, J. Yodoi, M. Mishima
  • Organizer: European Respiratory Society
  • Year and Date: 2010-09-21
• [Presentation] A single nucleotide polymorphism in NOD2 gene was associated with pathogenesis and severity of COPD (2010)
  • Author(s): D. Kinose, E. Ogawa, T. Hirota, I. Ito, S. Muro, Y. Hoshino, T. Hirai, H. Sakai, M. Tamari, M. Mishima
  • Organizer: European Respiratory Society Barcelona
  • Year and Date: 2010-09-19
• [Presentation] A single nucleotide polymorphism in NOD2 gene was associated with pathogenesis and severity of COPD (2010)
  • Author(s): 黄瀬大輔、小川恵美子、室繁郎
  • Organizer: ヨーロッパ呼吸器学会
  • Place of Presentation: バルセロナ(スペイン)
  • Year and Date: 2010-09-19
• [Presentation] 血清歯周病抗体価とCOPD(慢性閉塞性肺疾患)増悪との関連性 (2010)
  • Author(s): 高橋珠紀、室繁郎、三嶋理晃
  • Organizer: 第75回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 北九州国際会議場
  • Year and Date: 2010-06-25
• [Presentation] Oxidative stress augmented IL-32 gene upregulation in airway epithelial cells (2010)
  • Author(s): M. Kudo, MD, E. Ogawa, MD, PhD, A. Haruna, MD, D. Kinose, MD., Y. Hoshino, MD, PhD, S. Muro, MD. PhD., T. Hirai, MD, PhD, M. Mishima, MD, PhD
  • Organizer: American Thoracic Society
  • Year and Date: 2010-05-19
• [Presentation] Distinct responses against polyinosine-polycytidylic acid in smoke-exposed mouse strains with different susceptibility to emphysema (2010)
  • Author(s): N. Tanabe, MD, Y. Hoshino, MD, PhD, H. Kiyokawa, MD, S. Marumo, MD, E. Ogawa, MD, PhD, S. Muro, MD, PhD, T. Hirai, MD, PhD, M. Mishima, MD, PhD
  • Organizer: American Thoracic Society
  • Year and Date: 2010-05-18
• [Presentation] The effect of telling smokers their "lung age" on smoking quit rate at annual health checkup (2010)
  • Author(s): S. Marumo, MD1, S. Muro, MD. PhD. 1, A. Haruna, MD1, A. Sato, M. D., Ph. D. 2, E. Ogawa, MD, PhD1, Y. Hoshino, MD, PhD1, T. Hirai, MD, PhD1, M. Mishima, MD, PhD1, A. Sato, MD. PhD1
  • Organizer: American Thoracic Society Thematic Poster Session
  • Year and Date: 2010-05-17
• [Presentation] NOD2 SNPs associated with Crohn's disease were not found in Japanese COPD patients (2010)
  • Author(s): E. Ogawa, MD, PhD, M. Nishioka, MD., Y. Hoshino, MD, PhD, T. Hirai, MD, PhD, S. Muro, MD. PhD
  • Organizer: American Thoracic Society Thematic Poster Session
  • Year and Date: 2010-05-17
• [Presentation] 医逆流症症状とCOPD増悪 (2009)
  • Author(s): 室繁郎
  • Organizer: GERD研究会 第14回学術集会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-21
• [Presentation] 体質とCommon diseases体質とCOPD (2009)
  • Author(s): 室繁郎
  • Organizer: 第59回日本体質医学会総会
  • Year and Date: 2009-07-25
• [Presentation] 胃食道逆流症症状とCOPD増悪 (2009)
  • Author(s): D. Kinose, MD, E. Ogawa, MD, PhD, S. Muro, MD, PhD, A. Takahashi, MD, H. Sakai, MD, PhD, W. M. Elliott, PhD, J. C. Hogg, MD, PhD, M. Mishima, MD, PhD
  • Organizer: 第14回学術集会
  • Year and Date: 2009-05-29
• [Presentation] Three-Dimensional Lobar Distribution of Emphysema Assessed Using Computer Tomographic Data (2009)
  • Author(s): Three-Dimensional Lobar Distribution of Emphysema Assessed Using Computer Tomographic Data
  • Organizer: Poster Discussion
  • Year and Date: 2009-05-20
• [Presentation] Increased NOD1 and NOD2 Gene Expressions in Bronchial Epithelial Cells in COPD (2009)
  • Author(s): D. Kinose, MD, E. Ogawa, MD, PhD, S. Muro, MD, PhD, A. Takahashi, MD, H. Sakai, MD, PhD, W. M. Elliott, PhD, J. C. Hogg, MD, PhD, M. Mishima, MD, PhD
  • Organizer: Mini-Symposium
  • Year and Date: 2009-05-19
• [Presentation] Systemic Immune Activation by Polyinosine-Polycytidylic Acid Evokes Lung Inflammation Similar to COPD Exacerbation in Cigarette Smoke-Exposed Mice (2009)
  • Author(s): N. Tanabe, MD, Y. Hoshino, MD, Ph, S. Marumo, MD, I. Ito, MD, Ph, E. Ogawa, MD, Ph, S. Muro, MD, Ph, T. Hirai, MD, Ph, M. Mishima, MD, Ph
  • Organizer: Thematic Poster Session
  • Year and Date: 2009-05-17
• [Presentation] Pathophysiology of Cigarette Smoke Induced Emphysema after Smoking Cessation in a Murine Model (2009)
  • Author(s): MD, A. Sato, MD, PhD, I. Ito, MD, PhD, E. Ogawa, MD, PhD, S. Muro, MD, PhD, T. Hirai, MD, PhD, M. Mishima, MD, PhD
  • Organizer: Mini-Symposium
  • Year and Date: 2009-05-17