胃食管反流性咳嗽患者气道黏膜与分泌物中神经肽含量的变化

目的探讨气道神经源性炎症在胃食管反流性咳嗽(GERC)发病中的作用。方法20例GERC患者(GERC组),与10名正常人(正常对照组)和8例其他病因咳嗽伴有胃食管反流(GERD)患者(GERD组)分别作对比分析,观察GERC患者治疗前、后气道黏膜与分泌物中神经肽的变化。用酶联免疫吸附测定(ELISA)法测定痰上清液P物质(SP)、神经肽A(NKA)、神经肽B(NKB)的含量;用放射免疫法测定痰上清液降钙素基因相关肽(CGRP)的浓度。用免疫组化法检测气道黏膜、诱导痰细胞SP、NKA及SP受体(NK1)的表达,结果用半定量病理学方法表示。结果GERC组患者痰上清液SP、CGRP含量[(266±207)ng/L、(180±83)ng/L]显著高于正常对照组[(143±36)ng/L、(105±64)ng/L,P分别<0.05、<0.01]和GERD组[(130±11)ng/L、(89±16)ng/L,P分别<0.05、<0.01],NKA、NKB的含量各组间比较差异无统计学意义(P均>0.05);GERC组痰细胞SP、NK1和NKA的表达显著高于正常对照组(P分别<0.01、<0.05,<0.05)和GERD组(P均<0.05);GERC组气道黏膜SP的表达也显著高于GERD组(P<0.01)。治疗后,诱导痰细胞SP、NK1、NKA的表达较治疗前显著降低(P<0.01,<0.01或<0.05),痰上清液CGRP的含量也较治疗前显著降低(P<0.05)。结论GERC患者气道存在明显的神经源性炎症,治疗后神经肽趋于正常,提示神经源性炎症与GERC的发病密切相关。

The role of airway neurogenic inflammation in gastro-esophageal reflux induced cough

OBJECTIVE: To investigate the role of airway neurogenic inflammation in the pathogenesis of gastro-esophageal reflux induced cough (GERC). METHODS: Sputum was induced by hypertonic saline aerosol inhalation in 20 patients with GERC (GERC group), 10 healthy subjects (normal control group) and 8 patients with chronic cough due to other causes but complicated with gastro-esophageal reflux diseases (GERD, GERD group). Airway mucosal biopsy was performed in 6 patients with GERC and 4 patients with GERD using flexible fiberoptic bronchoscopy. The expression of substance P (SP), neurokinin 1 receptor and neurokinin A (NKA) in sputum cells and airway mucosa were detected by immunohistochemistry, and was assessed semi-quantitatively. SP, NKA, and NKB in the supernatant of induced sputum were measured with enzyme linked immunosorbent assay. Calcitonin gene-related peptide (CGRP) was measured with radioimmunoassay. RESULTS: The concentration of SP in the supernatant of induced sputum was significantly higher in GERC group [(266 +/- 207) ng/L] than those in normal control group [(143 +/- 36) ng/L, P < 0.05] and GERD group [(130 +/- 11) ng/L, P < 0.05], and the sputum supernatant concentration of CGRP in GERC group [(180 +/- 83) ng/L] was significantly higher than those in normal control group [(105 +/- 64) ng/L, P < 0.01] and GERD group [(89 +/- 16) ng/L, P < 0.01]. The expression of SP, NK-1 receptor and NKA in induced sputum cells in GERC group were significantly higher than those in normal control group (P < 0.01, < 0.05, < 0.05) and GERD group (all P < 0.05); Expressions of SP in airway mucosa was significantly higher in GERC group than in GERD group (P < 0.01). After treatment, the concentration of CGRP in the supernatant of sputum in GERC patients was significantly lower than that before treatment (P < 0.05); the expression of SP, NK-1 and NKA in the induced sputum cells were significantly lower than that before treatment (P < 0.01, P < 0.01 or P < 0.05). CONCLUSION: There is airway neurogenic inflammation in GERC patients, which maybe closely related to the development of GERC.