Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health & Science University, Portland, Oregon; and.
Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.
Am J Respir Crit Care Med. 2021 Feb 1;203(3):348-355. doi: 10.1164/rccm.201912-2347OC.
Chronic cough is characterized by frequent urges to cough and a heightened sensitivity to inhaled irritants. Airway sensory nerves trigger cough. We hypothesized that sensory nerve density is increased in chronic cough, which may contribute to excessive and persistent coughing. To measure airway nerve density (axonal length) and complexity (nerve branching, neuropeptide expression) in humans with and without chronic cough. Bronchoscopic human airway biopsies were immunolabeled for nerves and the sensory neuropeptide substance . Eosinophil peroxidase was also quantified given previous reports showing associations between eosinophils and nerve density. Three-dimensional image z-stacks of epithelium and subepithelium were generated using confocal microscopy, and from these z-stacks, total nerve length, the number of nerve branch points, substance expression, and eosinophil peroxidase were quantified within each airway compartment. Nerve length and the number of branch points were significantly increased in epithelium, but not subepithelium, in chronic cough compared with healthy airways. Substance expression was scarce and was similar in chronic cough and healthy airways. Nerve length and branching were not associated with eosinophil peroxidase nor with demographics such as age and sex in either group. Airway epithelial sensory nerve density is increased in chronic cough, suggesting sensory neuroplasticity contributes to cough hypersensitivity.
慢性咳嗽的特征是频繁的咳嗽冲动和对吸入性刺激物的敏感性增加。气道感觉神经引发咳嗽。我们假设慢性咳嗽患者的感觉神经密度增加，这可能导致过度和持续的咳嗽。测量有和没有慢性咳嗽的人的气道神经密度（轴突长度）和复杂性（神经分支，神经肽表达）。支气管镜下的人类气道活检被免疫标记为神经和感觉神经肽物质 P。由于之前的报告显示嗜酸性粒细胞与神经密度之间存在关联，因此也量化了嗜酸性粒细胞过氧化物酶。使用共聚焦显微镜生成上皮和上皮下的三维图像 z 堆栈，并且从这些 z 堆栈中，在每个气道隔室中定量测定总神经长度，神经分支点的数量，物质 P 的表达和嗜酸性粒细胞过氧化物酶。与健康气道相比，慢性咳嗽患者的上皮神经长度和分支点数量显着增加，但上皮下神经则没有。物质 P 的表达很少，在慢性咳嗽和健康气道中相似。神经长度和分支与嗜酸性粒细胞过氧化物酶或年龄和性别等人口统计学特征均无关联，无论在哪个组中。慢性咳嗽患者的气道上皮感觉神经密度增加，表明感觉神经可塑性有助于咳嗽高敏感性。
