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Pathophysiology of specific bronchial hyperresponsiveness

Research Project

Project/Area Number 07670662
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

FUJIMURA Masaki  Kanazawa University School of Medicine, The Third Department of Internal Medicine, Assistant Professor., 医学部・附属病院, 講師 (90190066)

Co-Investigator(Kenkyū-buntansha) YASUI Masahide  Kanazawa University School of Medicine, The Third Department of Internal Medicin, 医学部・附属病院, 助手 (60239746)
KASAHARA Kazuo  Kanazawa University School of Medicine, The Third Department of Internal Medicin, 医学部・附属病院, 助手 (30272967)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
KeywordsSpecific bronchial hyperresponsiveness / Alcohol-induced asthma / ultrasonically nebulized distillled water / beta-blockers / Autonomic nerve system / Neuropeptides / Lipid mediators / Guinea pigs / アルコール誘発気道収縮 / 交感神経遮断薬誘発気管支収縮 / 蒸留水吸入誘発気管支収縮 / 即時型アレルギー反応 / トロンボキサンA_2 / ロイコトリエン / 血小板活性化因子 / ヒスタミン / トロンボキサンA2
Research Abstract

1. Alcohol-induced bronchoconstriction in guinea pigs
(1) Acetaldehyde, a metabolite of ethanol, causes bronchoconstriction but ethanol does not.
(2) The acetaldehyde-induced bronchoconstriction is mediated via histamine release.
(3) A low dose of acetaldehyde, which does not cause bronchoconstriction, enhances non-specific bronchial responsiveness.
(4) Thromboxane A2 is involved in the acetaldehyde-induced non-specific bronchial hyperresponsiveness.
2. A guinea big model of propranolol-induced bronchoconstriction and the role of autonomic nerve system, chemical mediators and neuropeptides
(1) An inhalation of propranolo causes bronchoconstriction when it is inhaled 20 minutes after an aerosolized antigen provocation in passively sensitized guinea pigs.
This is the first animal model or propranolol-induced bronchoconstriction.
(2) Parasympathctic or alpha-adrenergic nerve activity is not involved in this response.
(3) Ncuropeptides such as substance P and neurokinin A do not take a part in this … More response.
(4) Lipid mediators, especially thromboxane A2, have an important role in this response.
3. A guinea-pig model of untrasonically nebulized distillled water (UNDW) -induced bronchoconstriction and the role of autonomic nerve system, chemical mediators and neuropeptides
(1) An inhalation of UNDW produces acute bronchoconstriction when it is inhaled 20 mimutes after an aerosolized antigen provocation in passively sensitized guinea pigs.
This is the first animal model of UNDW-induced bronchoconstriction.
(2) Parasympathetic nerve activity is not involved in this response.
(3) Histamine and substance P,but not neurokinin A,take a large part in this response.
(4) Thromboxane A2 does not have a role in this response.
4. Conclusion
Form these results, it is suggested that allergic airway response, or allergic airway inflammatory process, is important in development of specific bronchial responsiveness. Furthermore, the mechanism of specific bronchial hyperresponsiveness may be different each other, suggesting heterogeneity of contributing factors between several specific bronchial hyperresponsiveness in asthma. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (54 results)

All Other

All Publications (54 results)

  • [Publications] Fujimura M, et al: "Involvement of PAF in postallergic propranolol-induced bronchoconstriction in guinea-pigs" Eur Respir J. 9(10). 2064-2069 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M, et al: "Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs vivo." Clin Exp Allergy. 26(12). 1428-1435 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M, et al: "Peptide leukotrienes mediate acetaldehyde-induced bronchial hyper-responsiveness in guinea" Clin Exp Allergy. 27(1). 104-109 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M, et al: "Role of leukotrienes in post-allergic propranolol-induced bronchoconstriction in guinea pigs" Clin Exp Allergyxp Allergy. 27. 1219-1226 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M, et al: "A guinea-pig model of ultrasonically nebulized distilled water-induced bronchoconstriction." Eur Respir J. 10. 2237-2242 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M, et al: "Role of tachykinins in distilled water-induced bronchoconstriction in guinea-pigs." Clin Exp Allergy. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 藤村 政樹: "喘息の治療と受容体拮抗薬.In Medical Topics Series気道アレルギー'96" メディカルレビュー社東京, 9 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 明茂 治、藤村 政樹: "アルコール喘息:In気道アレルギー'97、牧野荘平、石川孝監修1997" メディカルレビュー社東京, 11 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Myou S,Fujimura M,Matsuda T.: "Aerosolized acetaldehyde, but not ethanol, induces histamine-mediated bronchoconstriction in guinea pigs" Clin Exp Allergy. 24 (2). 140-143 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Myou S,Fujimura M,Bando.T,Saito M,Matsuda T.: "Intravenous injection of acetaldehyde but not ethanol induces histamine-mediated bronchoconstriction in guinea pigs" Respiration. 62 (3). 143-147 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M,Myou S,Amemiya T,Tachibana H,Kita T,Matsuda T.: "Peptide leukotrienes mediate acetaldehyde-induced bronchial hyper-responsiveness in guinea pigs" Clin Exp Allergy. 27 (1). 104-109 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Myou S,Fujimura M,Nishi K,Ohka T,Matsuda T.: "Aerosolized acetaldehyde induces histamine-mediated bronchoconstriction in asthmatics." Am Rev Respir Dis. 148. 940-943 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Myou S,Fujimura M,Nishi K,Ohka T,Matsuda T.: "Potentiating effect of inhaled acetaldehyde, on bronchial responsiveness to methacholine in asthmatic subjects." Thorax. 49 (7). 644-648 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Myou S,Fujimura M,Nishi K,Watanabe K,Matsuda M,Ohka T,Matsuda T.: "Inhibitory effect of a selective thromboxane synthetase inhibitor, OKY-046, on acetaldehyde-induced bronchoconstriction in asthmatic patients." Chest. 106. 1414-1418 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Myou S,Fujimura M,Nishi K,Ohka T,Matsuda T.: "Inhibitory effect of terfenadine, a selective H1-histamine antagonist, on alcoholic beverage-induced bronchoconstriction in asthmatic patients." Eur Respir J. 8 (4). 619-623 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Myou S,Fujimura M,Kamio Y,Band T., Nakatsumi Y,Matsuda T.: "Repeated inhalation challenge with exogenous and endogenous histamine released by acetaldehyde inhalation in asthmatic patients." Am J Respir Crit Carc Med. 152 (2). 456-460 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Myou S,Fujimura M,Nishi K,Watanabe K,Matsuda M,Ohka T,Matsuda T.: "Effect of ethanol on airway caliber and nonspecific bronchial responsiveness in patients with alcohol-induced asthma." Allergy. 51. 52-55 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M,Myou S,Kamio Y,Matsuda T.: "Inhibitory effects of indomethacin on tachyphylaxis in response to acetaldehyde-induced bronchoconstriction in asthmatic patients." J Allergy Clin Immunol. 99 (5). 620-623 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Songur N,Fujimura M,Mizuhashi K,Saito M,Xiu Q,Matsuda T.: "Involvement of thromboxane A2 in propranolol-induced bronchoconstriction after allergic bronchoconstriction in guinea pigs." Am J Respir Crit Care Med. 149 (4). 1488-1493 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Songur N,Fujimura M,Mizuhashi K,Saito M,Matsuda T.: "Effect of AL-3264 on propranolol-induced bronchoconstriction in guinea pigs." J Lipid Mediators Cell Signaling. 11 (2). 175-185 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M,Tsujiura M,Songur N,Myou S,Matsuda T.: "Involvement of PAF in postallergic propranolol-induced bronchoconstriction in guinea pigs." Eur Respir J. 9 (10). 2064-2069 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M,Tsujiura M,Myou S,Ishiura Y,Matsuda T.: "Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs in vivo." Clin Exp Allergy. 26 (12). 1428-1435 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M,Songur N,Tsujiura M,Mizuhashi K,Myou S,Matsuda T.: "Role of leukotrienes in post-allergic propranolol-induced bronchoconstriction in guinea pigs." Clin Exp Allergy. 27. 1219-1226 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M,Amemiya T,Myou S,Mizuguchi M,Matsuda T.: "A guinea-pig model of ultrasonically nebulized distillled water-induced bronchoconstriction." Eur Respir J. 10. 2237-2242 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M,Amemiya T,Myou S,Mizuguchi M,Ishiura Y,Sasaki S,Matsuda T.: "Role of tachykinins in distillled water-induced bronchoconstriction in guinea-pigs." Clin Exp Allergy. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Fujimura M,et al: "Peptide leukotrienes mediate acetaldehyde-induced bronchial hyper-responsiveness in guinea pigs." Clin Exp Allergy. 27(1). 104-109 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujimura M,et al: "Inhibitory effects of indomethacin on tachyphylaxis in response to acetaldehyde-induced bronchoconstriction in asthmatic patients." J Allergy Clin Immunol. 99(5). 620-623 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujimura M,et al: "Role of leukotrienes in post-allergic propranolol-induced bronchoconstriction in guinea pigs." Clin Exp Allergy. 27. 1219-1226 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujimura M,et al: "A guinea pig model of ultrasonically nebulized distilled water-induced bronchoconstriction." Eur Respir J. 10. 2237-2242 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujimura M,et al: "Role of tachykinins in distilled water-induced bronchoconstriction in guinea-pigs." Clin Exp Allergy. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 明茂治、藤村政樹: "アルコール喘息:In気道アレルギー'97、牧野荘平、石川孝 監修1997" メディカルレビュー社 東京, 11 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujimura M,et al.: "Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea pigs in vivo." Clin Exp Allergy. 26. 357-362 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujimura M,et al.: "Effect of capsaicin inhalation on methacholine responsiveness in normal subjects." Clin Auton Res. 6. 45-48 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujimura M,et al.: "Female gender as a determinant of cough threshold to inhaled capsaicin." Eur Respir J. 9(8). 1624-1626 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujimura M,et al.: "Involvement of PAF in postallergic propranolol-induced bronchoconstriction in guinea-pigs." Eur Respir J. 9(10). 2064-2069 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujimura M,et al.: "Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs in vivo." Clin Exp Allergy. 26(12). 1428-1435 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujimura M,et al.: "Detection of eosinophils in hypertonic saline-induced sputum in patients with chronic nonproductive cough." J Asthma. 34(2). 119-126 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujimura M: "Bronchodilator and bronchoprotective effects of cilostazol in humans in vivo." Am J Respir Crit Care Med. 151. 222-225 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujimura M: "Additive effect of continuous low-dose ofloxacin on erythromycin therapy for sinobronchial syndrome." Drugs. 49(Suppl.2). 409-411 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujimura M: "Prostanoids and cough response to capsaicin in asthma and chronic bronchitis." Eur Respir J. 8. 1499-1505 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujimura M: "Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea pigs in vivo." Clinical Experimental Allergy. 26(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujimura M: "Effect of capsaicin inhalation on methacholine responsiveness in normal subjects." Clinical Autonomic Research. 5(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujimura M: "Involvement of thromboxane A2 in bronchial hyperresponsiveness of asthma." Pulmonary Pharmacology. 8(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Fujimura M: "Influence of sex, age, and pulmonary function on cough receptor sensitivity to inhaled capsaicin in nonsmoking, nonatopic,healthy subjects" Eur Respir J. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Xiou Q,Fujimura M: "Involvement of thromboxane A2 in bronchial hyperresponsiveness induced by interleukin-8 in guinea pigs" Clin Exp Allergy. 25. 51-59 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saito M,Fujimura M: "Role of thromboxane A2 and platelet-activating factor in allergic bronchoconstriction in guinea pig airway in vivo." J Lipid Mediators Cell signalling. 11. 1-12 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Songur N,Fujimura M: "Effect of AL-3264 on propranolol-induced bronchoconstriction in guinea pigs." J Lipid Mediators Cell signalling. 11. 175-185 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Myou S,Fujimura M: "Intravenous injection of acetaldehyde but not ethanol induces histamine-mediated bronchoconstriction in guinea pigs" Respiration. 62. 143-147 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Myou S,Fujimura M: "Inhibitory effect of terfenadine, a selective H1-histamine antagonist, on alcoholic beverage-induced bronchoconstriction in asthmatic patients." Eur Respir J. 8. 619-623 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Myou S,Fujimura M: "Repeated inhalation challenge with exogenous and endogenous histamine released by acetaldehyde inhalation in asthmatic patients." Am J Respir Crit Care Med. 152. 456-460 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishiura Y,Fujimura M: "Additive effect of continuous low-dose ofloxacin on erythromycin therapy for sinobronchial syndrome." Respiratory Medicine. 89. 677-684 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kurashima K,Fujimura M: "Effect of thromboxane A2 synthetase inhibitor, OKY-046, on sputum in chronic bronchitis and diffuse panbronchiolitis." Eur Respir J. 8. 1705-1711 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mizuguchi M,Fujimura M,: "Involvement of NK2^ハ receptors rather than NK1 receptors in bronchial hyperresponsiveness induced by allergic reaction in guinea-pigs." Br J Phamacol. 117. 443-448 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Myou S,Fujimura M,: "Effect of ethanol on airway caliber and nonspecific bronchial responsiveness in patients with alcohol-induced asthma." Allergy. (in press). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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