慢性特发性咳嗽患者的气道存在慢性炎症、气道壁重构以及气道上皮神经TRPV-1的表达。我们认为这些变化源自于生长因子的变化,如TGF-β和神经营养因子的表达增加。
随机选取13名持续性非哮喘性咳嗽患者,其中某些咳嗽患者接受过针对主要病因的相关特异性治疗,另选取19名正常的非咳嗽志愿者作为对照。采用支气管显微镜收集支气管肺泡灌洗液(BAL)和支气管活检。
与正常志愿者相比,咳嗽患者支气管肺泡灌洗液中的TGF水平显著增加,而神经生长因子(NGF)和脑源性神经生长因子(BDNF)无显著变化。此外,我们对活检标本进行TGF基因及蛋白表达检测。咳嗽患者气道平滑肌和上皮细胞观察到TGF mRNA表达,免疫组化显示患者ASM细胞中的TGF蛋白表达增加,伴随有转录因子smad 2/3的核表达。与正常志愿者相比,咳嗽患者基底膜厚度显著增加,而且BAL中TGF-β水平与基底膜厚度成正相关。
气道TGF-β可能参与了慢性特发性哮喘患者的气道重构,从而激发了咳嗽反射。
(刘国梁 审校)
Xie S, et al. Respir Res. 2009 May 22;10(1):40. [Epub ahead of print]
Expression of transforming growth factor-beta (TGF-beta) in chronic idiopathic cough
Xie S, Macedo P, Hew M, Nassenstein C, Lee KY, Chung KF.
ABSTRACT: In patients with chronic idiopathic cough, there is a chronic inflammatory response together with evidence of airway wall remodelling and an increase in airway epithelial nerves expressing TRPV-1. We hypothesised that these changes could result from an increase in growth factors such as TGF-beta and neurotrophins. We recruited 13 patients with persistent non-asthmatic cough despite specific treatment of associated primary cause(s), or without associated primary cause, and 19 normal non-coughing volunteers without cough as controls, who underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies. There was a significant increase in the levels of TGF in BAL fluid, but not of nerve growth factor(NGF) and brain-derived nerve growth factor(BDNF) compared to normal volunteers. Levels of TFG gene and protein expression were assessed in bronchial biopsies. mRNA expression for TGF was observed in laser-captured airway smooth muscle and epithelial cells, and protein expression by immunohistochemistry was increased in ASM cells in chronic cough patients, associated with an increase in nuclear expression of the transcription factor, smad 2/3. Subbasement membrane thickness was significantly higher in cough patients compared to normal subjects and there was a positive correlation between TGF-beta levels in BAL and basement membrane thickening. TGF-beta in the airways may be important in the airway remodelling changes observed in chronic idiopathic cough patients, that could in turn lead to activation of the cough reflex.