Mechanisms of heightened airway cough receptor sensitivity in eosinophilic bronchitis (atopic cough : eosinophilic bronchitis without asthma).

1.慢性无效性咳嗽的临床研究(1)提出了一种不同于咳嗽变异性哮喘的新的临床症状--“特应性咳嗽”。(2)支气管扩张剂治疗无效，支气管对乙酰甲胆碱的反应性在正常范围内，特应性咳嗽患者对吸入辣椒素的呼吸道咳嗽感受器敏感性增强。(3)根据下列发现，组织学特征被认为是大气道嗜酸性炎症：支气管肺泡灌洗液或支气管灌洗液中无嗜酸性粒细胞，活检的支气管标本中有少量嗜酸性粒细胞，(4)组胺hl拮抗剂和类固醇对特应性咳嗽有效。2.嗜酸性支气管炎的动物实验(1)多粘菌素B鼻腔给药建立豚鼠嗜酸性支气管炎模型，每周两次，持续3周。(2)呼吸道咳嗽感受器对吸入辣椒素的敏感性增加，但不增加对吸入组胺的反应性。(3)神经肽抑制剂(FK-224)和血栓素受体拮抗剂(S-1452)，但不是β2-激动剂(普罗特罗)。)显著降低气道咳嗽感受器的敏感性。(4)组胺hl拮抗剂(氮弹性蛋白)显著抑制气道咳嗽感受器的敏感性升高。提示持续性咳嗽(病理性咳嗽)的病理生理学机制至少有两种：特应性咳嗽大气道嗜酸性炎症引起的咳嗽感受器敏感性增高和咳嗽变异性哮喘大小气道嗜酸性炎症引起的支气管高反应性引起的支气管收缩。

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.ConclusionFrom 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.