Neurophenotypes in Airway Diseases Insights from Translational Cough Studies
Neurophenotypes in Airway Diseases Insights from Translational Cough Studies
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DOI：
10.1164/rccm.201508-1602oc
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发表时间：
2016-06-15
影响因子：
24.7
通讯作者：
Smith, Jaclyn A.
中科院分区：
文献类型：
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作者：
Belvisi, Maria G.;Birrell, Mark A.;Smith, Jaclyn A.
基本原理：大多数气道疾病，包括慢性阻塞性肺疾病（COPD），都与过度咳嗽有关。这可能是由于气道中的病理引起迷走神经传入激活增加的结果的程度（例如，炎症介质、过多的粘液）或改变的神经元表型是未知的。了解呼吸系统疾病是否与气道感觉神经功能障碍有关，有可能确定新的治疗靶点。目的：评估COPD患者对一系列吸入性刺激物的咳嗽反应变化，并在动物中建立模型以研究潜在机制。方法：COPD、健康吸烟者、难治性慢性咳嗽、哮喘患者对吸入刺激的咳嗽反应，在香烟烟雾（CS）暴露的豚鼠模型中，评估和比较迷走神经/气道神经和咳嗽反应。与健康志愿者相比，COPD患者对辣椒素的咳嗽反应增强，但对前列腺素E-2的反应降低。此外，不同的患者组都表现出不同的咳嗽反应调节模式。与这些研究结果一致，辣椒素引起更多的咳嗽CS暴露的豚鼠比对照组动物;类似的增加反应，观察到在离体迷走神经和神经元细胞体中的迷走神经节。然而，对前列腺素E-2的反应减少CS exposure.Conclusions：CS暴露能够诱导与COPD患者中观察到的咳嗽反应相一致的气道感觉神经表型转换的反应。此外，咳嗽反应的不同特征支持气道疾病中疾病特异性神经表型的概念。
Rationale: Most airway diseases, including chronic obstructive pulmonary disease (COPD), are associated with excessive coughing. The extent to which this may be a consequence of increased activation of vagal afferents by pathology in the airways (e.g., inflammatory mediators, excessive mucus) or an altered neuronal phenotype is unknown. Understanding whether respiratory diseases are associated with dysfunction of airway sensory nerves has the potential to identify novel therapeutic targets.Objectives: To assess the changes in cough responses to a range of inhaled irritants in COPD and model these in animals to investigate the underlying mechanisms.Methods: Cough responses to inhaled stimuli in patients with COPD, healthy smokers, refractory chronic cough, asthma, and healthy volunteers were assessed and compared with vagus/airway nerve and cough responses in a cigarette smoke (CS) exposure guinea pig model.Measurements and Main Results: Patients with COPD had heightened cough responses to capsaicin but reduced responses to prostaglandin E-2 compared with healthy volunteers. Furthermore, the different patient groups all exhibited different patterns of modulation of cough responses. Consistent with these findings, capsaicin caused a greater number of coughs in CS-exposed guinea pigs than in control animals; similar increased responses were observed in ex vivo vagus nerve and neuron cell bodies in the vagal ganglia. However, responses to prostaglandin E-2 were decreased by CS exposure.Conclusions: CS exposure is capable of inducing responses consistent with phenotypic switching in airway sensory nerves comparable with the cough responses observed in patients with COPD. Moreover, the differing profiles of cough responses support the concept of disease-specific neurophenotypes in airway disease.