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NEW STRATEGY BASED ON REGULATION OF OXTPATIVE STRESS IN TREATMENT OF BRONCHIAL ASTHMA

Research Project

Project/Area Number 13670611
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionOsaka City University

Principal Investigator

KANAZAWA Hiroshi  OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, RESEARCH ASSOCIATE, 大学院・医学研究科, 助手 (90332957)

Co-Investigator(Kenkyū-buntansha) HIRATA Kazuto  OSAKA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院・医学研究科, 助教授 (50173232)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsNITRIC OXIDE / AIRWAY HYPERREACTIVITY / β_2-ADRENQCEPTOR AGONIST / AIRWAY INFLAMMATION / 気管支喘息 / 運動誘発喘息 / 血管新生 / 血管透過性 / 窒素酸化物 / 気道内窒素酸化物 / 抗酸化能
Research Abstract

We have previously found that higher levels of nitrogen oxides in exhaled air and in induced sputum were found in asthmatics compared to normal control subjects, and that nitrogen oxides altered β_2 -adrenoceptor (β_-AR) function in an experimental animal model. Therefore, this study was designed to determine whether nitrogen oxides influence the bronchodilating activity of β_2-AR agonists in asthmatic patients. We simultaneously measured the levels of nitrogen oxides in exhaled air and in induced sputum in 20 asthmatic patients. The bronchodilating activity of β_2-AR agonists was expressed as a spontaneous recovery (pre- raethacholine) and recovery from the lowest value in FEV1 evoked by methacholine challenge (post-methacholine). For 1-week after the first study, 400 μg of beclomethasone dipropionate (BDP) twice daily was administered for all patients, and the above mentioned protocols were repeated. Recovery in FEV1 (pre-methacholine) after β_2-AR agonists was not significantly correlated with any baseline FEV1 and PC20 methacholine. Moreover, recovery in FEV1 (post-methacholine) after β_2-AR agonists was not also significantly correlated with maximal fall in FEV1 after methacholine challenge and PC20 methacholine. However, recovery in FEV1 after β_2-AR agonists was inversely correlated with NO levels in exhaled air, and concentration of nitrite and nitrate in induced sputum. After treatment with inhaled BDP for 1-week, there was no significant change in baseline FEV1. However, there was a significant decrease in the concentration of nitrite and nitrate in induced sputum. We found that change of nitrite and nitrate levels in induced sputum after 1-week BDP therapy was significantly correlated with change in bronchodilating activity of β_2-AR agonists between pre- and post-BDP therapy. We determined that nitrogen oxides in the airways reduced β_2-AR agonists-induced brochodilation in asthmatics.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Kanazawa H, et al.: "Nitrogen oxides reduce albuterol-induced bronchodilator in patients with bronchial asthma"Respiration. 69. 490-495 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kamazawa H, et al.: "Invdvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients"Thorax. 57. 885-888 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanazawa H, et al.: "Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma"Thorax. 57. 509-512 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanazawa H, et al.: "Vascular involvement in exercise-induced airway narrowing in patients with bronchial asthma"chest. 122. 166-170 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanazawa H, Hirata K, Yoshikawa J.: "Nitrogen oxides reduce albuterol-induced bronchodilation in patients with bronchial asthma."Respiration. 69. 490-495 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanazawa H, Hirata K, Yoshikawa J.: "Involvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients."Thorax. 57. 885-888 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanazawa H, Shiraishi S, Hirata K, Yoshikawa J.: "Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma"Thorax. 57. 509-512 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanazawa H, Asai K, Hirata K, Yoshikawa J.: "Vascular involvement in exercise-induced airway narrowing in patients with bronchial asthma."Chest. 122. 166-170 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kanazawa H, Shiraishi S, Hirata K, Yoshikawa J: "Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma"Thorax. 57. 509-512 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanazawa H, Asai K, Hirata K, Yoshikawa J: "Vascular involvement in exercise-induced airway narrowing in patients with bronchial asthma"Chest. 122. 166-170 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanazawa H, Hirata K, Yoshikawa J: "Nitrogen oxides reduce albuterol-induced bronchodilation in patients with bronchial asthma"Respiration. 69. 490-495 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanazawa H, Hirata K, Yoshikawa J: "Involvement of vascular endothelial growth factor in exercise-induced bronchoconstriction in asthmatic patients"Thorax. 57. 885-888 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanazawa H, Shiraishi S, Hirata K, Yoshikawa J: "Imbalance between nitrogen oxides levels and peroxynitrite inhibitory activity in chronic obstructive pulmonary disease"Thorax. 58. 106-109 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanazawa H, Mamoto K, Hirata K, Yoshikawa J: "Interferon therapy induces the improvement of lung function by inhaled corticosteroid therapy in asthmatic patients with chronic hepatitis C virus infection"Chest. 123. 600-603 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiroshi Kanazawa et al.: "Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma"Thorax. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroshi Kanazawa et al.: "Vascular involvement in exercise-induced airway narrowing in patients with bronchial asthma"Chest. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroshi Kanazawa et al.: "Nitrogen oxides reduce albuterol-induced bronchodilation in patients with b ronchial asthma"Respiration. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroshi Kanazawa et al.: "Association between the angiotensin converting enzyme gene polymorphisms and tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease"Chest. 121. 697-701 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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