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

环境真菌和 IgE 非介导机制在特应性发作中的重要性

• 批准号: 17607003
• 负责人: FUJIMURA Masaki
• 金额: $ 2.53万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17607003/
• 关键词: chronic 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

I. Clinical research1) 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 coughExhaled 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 research1) 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

1)环境真菌担子菌真菌在慢性咳嗽中的作用(1)在以往的研究中，担子菌真菌是重症特应性咳嗽的重要环境真菌，DNA序列分析显示，从难治性慢性咳嗽患者的痰中培养的真菌为Bjerkandera adusta。(2) 20%的特应性咳嗽患者咽拭子真菌培养检出担子菌。发病率仅次于念珠菌。(3)成功制备担子菌属真菌抗原提取物。抗原提取液的即刻型皮肤反应在20%的特应性咳嗽患者中呈阳性，显著高于非特应性健康人（5%）。(4) 8例难治性慢性咳嗽患者痰液产生adusta Bjerkandera培养，淋巴细胞刺激试验和真菌抗原吸入激发试验均呈阳性，而皮肤反应仅3例呈阳性。这些发现表明，lgE非介导性过敏反应在真菌相关的慢性咳嗽中很重要。2)特应性咳嗽中呼出一氧化氮（NO）浓度是嗜酸性气道炎症的生物标志物，在支气管哮喘、咳嗽变异性哮喘和非哮喘性嗜酸性支气管炎中，一氧化氮（NO）水平升高。我们研究了与支气管哮喘和咳嗽变异性哮喘相比，特应性咳嗽患者呼出一氧化氮水平是否升高。与支气管哮喘和咳嗽变异性哮喘相比，特应性咳嗽患者呼出一氧化氮水平明显降低。基础研究1)建立特应性咳嗽和咳嗽变异性哮喘豚鼠模型。神经激肽和组胺在特应性咳嗽模型中起重要作用，而白三烯在咳嗽变异性哮喘模型中起重要作用。2)我们假设咳嗽发作是气道的机械应力，影响咳嗽反射的敏感性。麻醉和人工通气豚鼠反复给予短暂快速负压。负压应激后6 h，吸入性辣椒素咳嗽反射敏感性升高，与中性粒细胞气道炎症有关。对气道的咳嗽应激形成一个自我延续的咳嗽反射循环，抗原诱导的咳嗽反射敏感性增加导致病理性咳嗽，而咳嗽反过来又放大了咳嗽反射敏感性。少

项目成果

Exhaled nitric oxide (NO) levels in patients with atopic cough and cough variant asthma

特应性咳嗽和咳嗽变异性哮喘患者呼出一氧化氮 (NO) 水平

• 发表时间: 2008
• 期刊: Respirology 13 (3)
• 作者: Fujimura M;et al
• 通讯作者: et al

Eosinophilic pneumonia caused by Aspergillus niger:Is oral cleansing with amphotericin B efficacious for preventing allergic pneumonitis from relapsing

黑曲霉引起的嗜酸性粒细胞性肺炎：两性霉素B口腔清洁能否有效预防过敏性肺炎复发

• 发表时间: 2008
• 期刊: Journal of Asthyma (印刷中掲載確定)
• 作者: 0gawa H;Fujimura M;Tofuku Y;Kitagawa M.
• 通讯作者: Kitagawa M.

Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs

• DOI: 10.1016/j.pupt.2006.05.004
• 发表时间: 2007-01-01
• 期刊: PULMONARY PHARMACOLOGY & THERAPEUTICS
• 影响因子: 3.2
• 作者: Fujimura, Masaki;Liu, Qi
• 通讯作者: Liu, Qi

Ambroxol for the prevention of acute upper respiratory disease: a long-term single center trial

氨溴索预防急性上呼吸道疾病：长期单中心试验

• 发表时间: 2006
• 期刊: Clin Exp Med 6 (2)
• 作者: Nobata K;Fujimura M;et al
• 通讯作者: et al

呼吸器疾患Ver.5 State of arts

呼吸系统疾病 Ver.5 艺术现状

• 发表时间: 2007
• 作者: 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;藤村 政樹;藤村 政樹
• 通讯作者: 藤村 政樹