Departments of Respiratory Medicine Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Respirology. 2011 May;16(4):645-52. doi: 10.1111/j.1440-1843.2011.01952.x.
The aim of this study was to explore the pathogenesis of chronic cough caused by non-acid reflux.
Seven patients with chronic cough due to non-acid reflux, 12 patients with chronic cough due to acid reflux, 10 patients with gastro-oesophageal reflux disease without cough and 12 healthy volunteers were recruited for the study. All subjects underwent oesophageal multi-channel intraluminal impedance measurements combined with pH monitoring, and assessment of cough reflex sensitivity to capsaicin and induced sputum cytology. The concentrations of substance P, mast cell tryptase, prostaglandin D2 and histamine in induced sputum were measured by ELISA.
Cough threshold C2 and C5 did not differ between patients with chronic cough due to non-acid or acid reflux, but the values were significantly lower than those for patients with gastro-oesophageal reflux disease without cough and healthy volunteers. Weakly acidic reflux episodes were obviously more frequent in patients with chronic cough due to non-acid reflux than in the other three groups. Sputum substance P and mast cell tryptase concentrations were remarkably increased in patients with chronic cough, but were similar for those with cough due to non-acid or acid reflux. There were significant inverse correlations between substance P levels and cough threshold C2 or C5 in patients with cough due to non-acid or acid reflux, and between mast cell tryptase levels and cough threshold C2 in patients with cough due to acid reflux.
Chronic cough due to non-acid reflux may be related to cough reflex hypersensitivity caused by neurogenic airway inflammation and mast cell activation, in which weakly acidic reflux is possibly a major factor.
本研究旨在探讨非酸性反流引起的慢性咳嗽的发病机制。
本研究纳入了 7 例非酸性反流性慢性咳嗽患者、12 例酸性反流性慢性咳嗽患者、10 例无咳嗽的胃食管反流病患者和 12 名健康志愿者。所有受试者均接受食管多通道腔内阻抗测量联合 pH 监测,并评估咳嗽反射对辣椒素的敏感性和诱导痰细胞学。通过 ELISA 测量诱导痰中 P 物质、肥大细胞胰蛋白酶、前列腺素 D2 和组胺的浓度。
非酸性或酸性反流性慢性咳嗽患者的咳嗽阈值 C2 和 C5 无差异,但均明显低于无咳嗽的胃食管反流病患者和健康志愿者。非酸性反流性慢性咳嗽患者弱酸性反流事件明显多于其他三组。慢性咳嗽患者的痰中 P 物质和肥大细胞胰蛋白酶浓度明显增加,但非酸性或酸性反流性慢性咳嗽患者之间无差异。非酸性或酸性反流性慢性咳嗽患者的 P 物质水平与咳嗽阈值 C2 或 C5 之间,以及酸性反流性慢性咳嗽患者的肥大细胞胰蛋白酶水平与咳嗽阈值 C2 之间存在显著负相关。
非酸性反流性慢性咳嗽可能与神经源性气道炎症和肥大细胞激活引起的咳嗽反射敏感性增加有关,其中弱酸性反流可能是一个主要因素。