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Importance of environmental fungi and IgE non-mediated mechanism in atopic eough

Research Project

Project/Area Number 17607003
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field アレルギー
Research InstitutionKanazawa University

Principal Investigator

FUJIMURA Masaki  Kanazawa University, Graduate School of Medicine, Associated Professor (90190066)

Co-Investigator(Kenkyū-buntansha) OGAWA Haruhiko  Kanazawa University, Saiseikai Kanazawa Hospital, Respiratory Medicine, Director (70401908)
AKIYAMA Kazuo  Kanazawa University, National Hospital Organization Sagamihara National Hospital, Clinical research Center for Allergy and Rheumatology, National Director (70372084)
MAKIMURA Kouichi  Teikyo University, Graduate School of Medical Science Institute of Medical Mycology and Genome Research Center, Department of Molecular Biology and Gene Diagnosis, Associate Professor (00266347)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,960,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordschronic cough / atopic cough / environmental fungi / IgE non-mediated / Bjerkandera adusta / 難治性慢性咳嗽 / IgE非依存性アレルギー反応
Research Abstract

I. Clinical research
1) Importance of environmental fungi, basidiomycetous fungi, in chronic cough
(1) In previous studies basidiomycetous fungi had been documented as important environmental fungi in severer cases of atopic cough, The DNA sequence analysis revealed that the fungi which were cultured from sputum of patients with intractable chronic cough was Bjerkandera adusta.
(2) Basidiomycetous fungi was detected from fungal culture of pharyngeal swab in 20% of patients with atopic cough. The rate was the second following Candida.
(3) We succeeded to prepare the antigen extract of basidiomycetous fungi. Immediate type skin reaction using the antigen extract solution was positive in 20% of patients with atopic cough, which was significantly higher than that (5%) in non-atopic healthy subjects.
(4) In 8 patients with intractable chronic cough whose sputum yielded Bjerkandera adusta cultured, lymphocyte stimulation test and inhalation provocation test using the fungal antigen were positive … More while the skin reaction was positive in only 3 patients. These findings suggest that lgE non-mediated allergic reaction is important in the fungal-associated chronic cough.
2) Exhaled nitric oxide (NO) concentration in atopic cough
Exhaled nitric oxide (NO) is a biomarker of eosinophilic airway inflammation and the levels have been shown to be elevated in bronchial asthma, cough variant asthma and non-asthmatic eosinophilic bronchitis. We investigated whether the exhaled NO levels were increased in atopic cough in comparison with those in bronchial asthma and cough variant asthma. The exhaled NO levels were significantly lower in atopic cough compared with bronchial asthma and cough variant asthma.
II. Basic research
1) We developed guinea pig models of atopic cough and cough variant asthma. Neurokinins and histamine were important in the atopic cough model while leukotrienes were important in the cough variant asthma model.
2) We hypothesized that cough attacks are mechanical stress to the airways and influence the cough reflex sensitivity. Transient rapid negative pressure was repeatedly given to anesthetized and artificially ventilated guinea pigs. Cough reflex sensitivity to inhaled capsaicin was increased 6 hours after the negative pressure stress which was associated with neutrophilic airway inflammation. Cough stress to airway makes a self-perpetuating cough-reflex cycle, in which antigen-induced increase in cough reflex sensitivity results in pathologic cough, and the cough in turn amplifies cough reflex sensitivity. Less

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (44 results)

All 2008 2007 2006 2005

All Journal Article (35 results) (of which Peer Reviewed: 8 results) Presentation (3 results) Book (6 results)

  • [Journal Article] Effect of montelukast in a guinea pig model of cough variant asthma2008

    • Author(s)
      Nishitsuji M, Fujimura M, (他2名)
    • Journal Title

      Pulm Pharmacol Ther 21

      Pages: 142-145

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Exhaled nitric oxide (NO)levels in patients with atopic cough and cough variant asthma2008

    • Author(s)
      Fujimura M, (他6名)
    • Journal Title

      Respirology 13

      Pages: 359-364

    • NAID

      120001135522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of pressure stress applied to the airway on cough reflex sensitivity in guinea pigs2008

    • Author(s)
      H Hara J, Fujimura M, (他7名, 2番目)
    • Journal Title

      Am J Respir Crit Care Med 177

      Pages: 585-592

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of montelukast in a guinea pig model of cough variant asthma2008

    • Author(s)
      Nishitsuji M, Fujimura M, et al
    • Journal Title

      Pulm Pharmacol Ther.2008 21(1)

      Pages: 142-145

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of pressure stress applied to the airway on cough reflex sensitivity in guinea pigs2008

    • Author(s)
      Hara J, Fujimura M, et al
    • Journal Title

      Am J Respir Crit Care Med 177 (6)

      Pages: 585-592

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Exhaled nitric oxide (NO) levels in patients with atopic cough and cough variant asthma2008

    • Author(s)
      Fujimura M, et al
    • Journal Title

      Respirology 13 (3)

      Pages: 359-364

    • NAID

      120001135522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effect of an orally active Th2 cytokine inhibitor, suplatast tosilate, on "atopic cough"2008

    • Author(s)
      Ishiura Y, Fujmura M, et al
    • Journal Title

      Arzneim Forsch/Drug Research 58 (6)

      Pages: 297-302

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sputum eosinophilia, airway hyperresponsiveness and airway narrowing in young adults with former asthma2008

    • Author(s)
      Hara J, Fujimura M, et al
    • Journal Title

      Allergol Int. 57(3)

      Pages: 211-217

    • NAID

      10024419767

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bronchoconstriction-triggered cough in conscious guinea pigs2008

    • Author(s)
      Ohkura N, Fujimura M, et al.
    • Journal Title

      Exp Lung Res (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sputum eosinophilia, airway hyperresponsiveness and airway narrowing in young adults with formeer asthma2008

    • Author(s)
      Hara J, Fujimura M, Myou S, Abo M, Furusho S, Oribe Y, Nobata K, Ohkura N. Herai Y. Yasui M. Kasahara K.
    • Journal Title

      Allergology International (印刷中掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effect of pressure stress to airway on cough reflex sensitivity in guinea pigs2008

    • Author(s)
      Hara J, Fujimura M, Ueda A, Myou S, Oribe Y, Ohkura N, Kita T, Yasui M, Kasahara K.
    • Journal Title

      Am J Respir Crit Care Med 177(6)

      Pages: 585-592

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exhaled nitric oxide(NO)levels in patients with atopic cough and cough variant asthma2008

    • Author(s)
      Fujimura M, Ohkura N, Abo M, Furusho S, Waseda Y, Ichikawa Y, Hara J.
    • Journal Title

      Respirology 13(3)

      Pages: 359-364

    • NAID

      120001135522

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of an orally active Th2 cytokine inhibitor,suplatast tosilate,on"atopic cough"2008

    • Author(s)
      Ishiura Y, Fujimura M, Yamamoto H, Nobata K, Ishiguro T, Ogawa H, Myou S
    • Journal Title

      Arzneimittel-Forschung/Drug Research (印刷中掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eosinophilic pneumonia caused by Aspergillus niger:Is oral cleansing with amphotericin B efficacious for preventing allergic pneumonitis from relapsing2008

    • Author(s)
      0gawa H, Fujimura M, Tofuku Y, Kitagawa M.
    • Journal Title

      Journal of Asthyma (印刷中掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of montelukast in a guinea pig model of cough variant asthma2008

    • Author(s)
      Nishitsuji M, Fujimura M, Oribe Y, Nakao S.
    • Journal Title

      Pulm Pharmacol Ther 21(1)

      Pages: 142-145

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs2008

    • Author(s)
      Fujimura M, Liu Q.
    • Journal Title

      Pulmonary Pharmacology & Therapeutics 20(5)

      Pages: 543-548

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway2007

    • Author(s)
      Ishiura Y, Fujimura M, et al
    • Journal Title

      Cough 3

      Pages: 2-2

    • NAID

      120001138253

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs.2007

    • Author(s)
      Fujimura M, Liu Q
    • Journal Title

      Pulmonary Pharmacology & Therapeutics 20 (5)

      Pages: 543-548

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Surfactant degradation activity in bronchoalveolar lavage fluid from guinea pigs challenged with aerosolized antigen2007

    • Author(s)
      Abo M, Kurashima K, Fujimura M, et al
    • Journal Title

      Respirology 12 (6)

      Pages: 828-833

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs2007

    • Author(s)
      Fujimura M, Liu Q.
    • Journal Title

      Pulmonary Pharmacology and Therapeutics (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of montelukast in a guinea pig model of cough variant asthma2007

    • Author(s)
      Nishitsuji M, Fujimura M, Oribe Y, Nakao S
    • Journal Title

      Pulmonary Pharmacology and Therapeutics (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway2007

    • Author(s)
      Ishiura Y, Fujimura M, Nobata K, Oribe Y, Abo M, Myou S
    • Journal Title

      Cough 3・2

    • NAID

      120001138253

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Longitudinal changes of pulmonary function and bronchial responsiveness in cough variant as thma treated with bronchodilators alone2006

    • Author(s)
      Nobata K, Fujimura M, et al
    • Journal Title

      Allergy & Asthma Proceedings 27

      Pages: 479-485

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Eosinophilic inflammation and remodeling of lower airway, bronchial responsiveness and cough reflex sensitivity in non-asthmatic subjects with nasal allergy2006

    • Author(s)
      Hara J, Fujimura M, et al
    • Journal Title

      Int Arch Allergy Immunol 140 (4)

      Pages: 327-333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ambroxol for the prevention of acute upper respiratory disease: a long-term single center trial2006

    • Author(s)
      Nobata K, Fujimura M, et al
    • Journal Title

      Clin Exp Med 6 (2)

      Pages: 79-83

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-inducedasthma2006

    • Author(s)
      Furusho S, Myou S, Fujimura M, et al
    • Journal Title

      Clin Exp Allergy 36 (10)

      Pages: 1294-1302

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Longitudinal changes of pulmonary function and bronchial responsiveness in cough variant asthma treated with bronchodilators alone2006

    • Author(s)
      Nobata K, Fujimura M, Tsuji H, Ishiura Y, Myou S, Nakao S, Takazakura E
    • Journal Title

      Allergy & Asthma Proceedings 27

      Pages: 479-485

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Eosinophilic inflammation and remodeling of lower airway, bronchial responsiveness and cough reflex sensitivity in non-asthmatic subjects with nasal allergy2006

    • Author(s)
      Hara J, Fujimura M, Myou S, Furusho S, Abo M, Oribe Y, Ohkura N, Herai Y, Sone T, Waseda Y, Nobata K, Yasui M, Kasahara K
    • Journal Title

      International Archives of Allergy and Immunology 140・4

      Pages: 327-333

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma2006

    • Author(s)
      Furusho S, Myou S, Fujimura M, Kita T, Yasui M, Kasahara K, Nakao S, Takehara K, Sato S
    • Journal Title

      Clin Exp Allergy 36・10

      Pages: 1294-1302

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Longitudinal changes of pulmonary function and bronchial responsiveness in cough variant asthma treated with bronchodilators alone2006

    • Author(s)
      Nobata K, Fujimura M, Tsuji H, Ishiura Y, Myou S, Nakao S, Takazakura E
    • Journal Title

      Allergy & Asthma Proceedings (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Eosinophilic inflammation and remodeling of lower airway, bronchial responsiveness and cough reflex sensitivity in non-asthmatic subjects with nasal allergy2006

    • Author(s)
      Hara J, Fujimura M, Myou S, Furusho S, Abo M, Oribe Y, Ohkura N, Herai Y, Sone T, Waseda Y, Nobata K, Yasui M, Kasahara K
    • Journal Title

      International Archives of Allergy and Immunology (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Change in bronchial responsiveness and cough reflex sensitivity in patients with cough variant asthma : effect of inhaled corticosteroids : a retrospective parallel group obervation2005

    • Author(s)
      Fujimura M, Oribe Y, Hara J, Myou S.
    • Journal Title

      Cough (Online Journal) 1:5

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs2005

    • Author(s)
      Hara J, Fujimura M, Myou S, Oribe Y, Furusho S, Kita T, Nobata K, et al.
    • Journal Title

      Cough (Online Journal) 1:6

    • NAID

      120001138444

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhaled lysophosphatidylcholine directly provokes bronchoconstriction in guinea pigs2005

    • Author(s)
      Nobata K, Kurashima K, Fujimura M, Abe M, Ishiura Y, Kasahara K, Nakao S.
    • Journal Title

      Eur J Pharmacol 520;1-3

      Pages: 150-155

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Phosphodiesterase 3 inhibition and cough in elderly asthmatics2005

    • Author(s)
      Ishiura Y, Fujimura M, Nobata K, Abo M, Oribe T, Myou S, Nakamura H.
    • Journal Title

      Cough (Online Journal) 1:11

    • NAID

      120001138252

    • Related Report
      2005 Annual Research Report
  • [Presentation] Eosinophilic bronchitis : Prevalence and long-term outcomes2008

    • Author(s)
      Masaki. Fujimura
    • Organizer
      13th Congress for the Asian Pacific Society of Respirology
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2008-11-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Eosinophilic bronchitis: Prevalence and long-term outcomes2008

    • Author(s)
      Fujimura M
    • Organizer
      13th Congress for the Asian Pacific Society of Respirology
    • Place of Presentation
      Queen Sirikit National Convention Center, Bangkok, Thailand
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Exhaled NO levels in patients with chronic cough in Japan2006

    • Author(s)
      Hara J, Fujimura M, Myou S, Abo M, Furusho S, Oribe Y, Ohkusa N. Herai Y, Waseda Y, Ichikawa Y, Yasui M, Kasahara K, Nakao S
    • Organizer
      The 11th Congress of the Asian Pacific Society of Respirology
    • Place of Presentation
      Kyoto
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 慢性咳嗽 呼吸器疾患Ver. 5 State of Arts2007

    • Author(s)
      藤村 政樹
    • Publisher
      医歯薬出版株式会社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 呼吸器疾患Ver.5 State of arts2007

    • Author(s)
      藤村 政樹
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2007 Annual Research Report
  • [Book] 新臨床研修ガイドラインに基づく呼吸器内科Q&A2007

    • Author(s)
      藤村 政樹
    • Publisher
      総合医学社
    • Related Report
      2007 Annual Research Report
  • [Book] 呼吸器疾患:最新の治療2007-20092007

    • Author(s)
      藤村 政樹
    • Publisher
      南江堂
    • Related Report
      2007 Annual Research Report
  • [Book] 咳喘息 : 呼吸器疾患 Ver.5-State of arts2007

    • Author(s)
      藤村政樹
    • Total Pages
      3
    • Publisher
      医歯薬衆出版株式会社、東京
    • Related Report
      2006 Annual Research Report
  • [Book] 慢性咳嗽の診断と治療に関する指針.(藤村政樹 監修)2006

    • Author(s)
      藤村政樹, 亀井淳三, 内田義之, 新実彰男, 内藤建晴
    • Total Pages
      42
    • Publisher
      日本咳嗽研究会・アトピー咳嗽研究会発行、前田書店、金沢
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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