| Project/Area Number |
04807055
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
FUJIMURA Masaki Kanazawa University School of Medicine, The Third Department of Internal Medicine, Assistant Professor., 医学部付属病院, 講師 (90190066)
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| Co-Investigator(Kenkyū-buntansha) |
NISHI Kouichi Ishikawa Prefectual Hospital, Division of Pulmonary Medicine, Head., 呼吸器内科, 医長
小川 晴彦 富山赤十字病院, 内科, 医師
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | Chronic nonproductive cough / Pathophysiology / Cough receptor sensitivity / Bronchial responsiveness / Atopic cough / Cough variant asthma / Eosinophilic bronchitis / 咳嗽 / ニューロペプチド / トロンボキサンA_2 / カプサイシン / シクロオキシゲナーゼ代謝産物 / モルモット |
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| Research Abstract |
1.Clinical study on chronic nonproductive cough
(1) A new clinical entity named as "ATOPIC COUGH" has been proposed, which is different from cough variant asthma.
(2) Bronchodilator therapy is ineffective, bronchial responsiveness to methacholine is within normal range, and airway cough receptor sensitivity to inhaled capsaicin is heightened in atopic cough.
(3) The histologic feature is considered to be large airway eosinophilic inflammation according to the following findings : no eosinophils in bronchoalveolar lavage fluid or bronchial lavage fluid, small number of eosinophils in biopsied bronchial specimens, and almost same number of eosinophils in hypertonic saline-induced sputum as bronchial asthma.
(4) Histamine Hl-antagonists and steroids are effective for the treatment of atopic cough.
2.Animal experiment on eosinophilic bronchitis
(1) Eosinophilic bronchitis model of guinea pigs was successfully developed by intranasal administration of polymycin B twice a week for 3 weeks.
(2) Airway cough receptor sensitivity to inhaled capsaicin was heightened but bronchial responsiveness to inhaled histamine was not increased in this model.
(3) A neuropeptide inhibitor (FK-224) and a thromboxane receptor antagonist (S-1452) but not a beta2-agonist (procaterol) significantly reduced the heightened airway cough receptor sensitivity.
(4) A histamine Hl-antagonist (azelastin) significantly suppressed the heightened airway cough receptor sensitivity.
3.Conclusion
From these results, it is suggested that there are at least 2 different mechanisms for the pathophysiology of persistent nonproductive cough (pathological cough) : heightened airway cough receptor sensitivity induced by eosinophilic inflammation of the large airway in atopic cough and bronchoconstriction based on bronchial hyperresponsiveness induced by eosinophilic inflammation of the central to peripheral airways in cough variant asthma.
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