Hutchinson Nicola-Xan, Gibbs Allen, Tonks Amanda, Hope-Gill Benjamin D
Department of Respiratory medicine, Princess of Wales Hospital, Bridgend, United Kingdom.
Department of Histopathology, Cardiff and Vale University Health Board, Cardiff, United Kingdom.
PLoS One. 2017 Nov 17;12(11):e0187847. doi: 10.1371/journal.pone.0187847. eCollection 2017.
Dry cough is a common symptom described in patients with Idiopathic Pulmonary Fibrosis (IPF) and impairs quality of life. The exact mechanisms causing cough in IPF remain unclear, however evidence suggests altered cough neurophysiology and sensitisation plays a role; IPF patients have an enhanced cough reflex sensitivity to inhaled capsaicin. The Transient Receptor Potential Vanniloid-1 channel (TRPV-1) has a role in the cough reflex and airway expression is increased in patients with chronic cough. The Ankyrin-1 receptor (TRPA-1) is often co-expressed. It was hypothesised that, like chronic cough patients, IPF patients have increased airway TRP receptor expression. Bronchial biopsies were obtained from 16 patients with IPF, 11 patients with idiopathic chronic cough and 8 controls without cough. All other causes of cough were rigorously excluded. Real-time quantitative Polymerase Chain Reaction was used to detect TRPV-1 and TRPA-1 mRNA expression with Immunohistochemistry demonstrating protein expression. Mean TRPV-1 and TRPA-1 gene expression was higher in IPF patients compared with controls, but the difference did not reach statistical significance. Immunostaining supported these findings. This study suggests that structural up-regulation of central airway TRP receptors is not the key mechanism for cough in IPF patients. It is probable that IPF cough results from altered neuronal sensitivity at multiple levels of the cough pathway.
干咳是特发性肺纤维化(IPF)患者常见的症状,会损害生活质量。IPF患者咳嗽的确切机制尚不清楚,然而有证据表明咳嗽神经生理学改变和致敏作用发挥了作用;IPF患者对吸入辣椒素的咳嗽反射敏感性增强。瞬时受体电位香草酸亚型1通道(TRPV-1)在咳嗽反射中起作用,慢性咳嗽患者气道中该通道的表达增加。锚蛋白1受体(TRPA-1)常与之共同表达。据推测,与慢性咳嗽患者一样,IPF患者气道中TRP受体表达增加。从16例IPF患者、11例特发性慢性咳嗽患者和8例无咳嗽的对照者中获取支气管活检组织。严格排除所有其他咳嗽原因。采用实时定量聚合酶链反应检测TRPV-1和TRPA-1 mRNA表达,免疫组织化学检测蛋白表达。与对照组相比,IPF患者TRPV-1和TRPA-1基因的平均表达较高,但差异无统计学意义。免疫染色支持这些发现。本研究表明,中央气道TRP受体的结构上调不是IPF患者咳嗽的关键机制。IPF咳嗽可能是由咳嗽通路多个水平的神经元敏感性改变所致。