哮喘气道上皮重塑与炎症的双向相互作用
2021/06/18
摘要
哮喘是一种慢性气道疾病，长期以来被认为主要是一种炎症。因此，目前的治疗干预主要集中于解决炎症。然而，哮喘治疗的主要手段既不能完全改善肺功能，也不能预防疾病恶化，这表明其他因素参与其中。一个新兴的概念现在认为，哮喘的另一个主要病理特征气道重塑与哮喘发病机制中的炎症同样重要。与哮喘相关的结构变化包括破坏上皮完整性、上皮下纤维化、杯状细胞增生/化生、平滑肌肥大/增生和增强的血管分布。这些改变被假设为导致哮喘个体的气道高反应性、气道阻塞、气流受限和肺功能的进行性下降。因此，单独靶向炎症不足以提供最佳的临床益处。在这里，我们回顾了哮喘气道重塑，重点是气道上皮，这对维持健康的呼吸系统至关重要，也是对抗吸入刺激物的主要防御。在哮喘中，气道上皮是炎症的介质和靶标，在其下游效应中表现出重塑和导致的阻塞。我们还强调了治疗靶向气道结构改变的潜在益处。由于在其他易损伤和炎症的组织和器官中也观察到病理性组织重塑，因此我们的讨论可能具有哮喘和肺部疾病以外的意义。
Bidirectional interaction of airway epithelial remodeling and inflammation in asthma
Asoka Banno, Aravind T Reddy , Sowmya P Lakshmi , Raju C Reddy
Abstract
Asthma is a chronic disease of the airways that has long been viewed predominately as an inflammatory condition. Accordingly, current therapeutic interventions focus primarily on resolving inflammation. However, the mainstay of asthma therapy neither fully improves lung function nor prevents disease exacerbations, suggesting involvement of other factors. An emerging concept now holds that airway remodeling, another major pathological feature of asthma, is as important as inflammation in asthma pathogenesis. Structural changes associated with asthma include disrupted epithelial integrity, subepithelial fibrosis, goblet cell hyperplasia/metaplasia, smooth muscle hypertrophy/hyperplasia, and enhanced vascularity. These alterations are hypothesized to contribute to airway hyperresponsiveness, airway obstruction, airflow limitation, and progressive decline of lung function in asthmatic individuals. Consequently, targeting inflammation alone does not suffice to provide optimal clinical benefits. Here we review asthmatic airway remodeling, focusing on airway epithelium, which is critical to maintaining a healthy respiratory system, and is the primary defense against inhaled irritants. In asthma, airway epithelium is both a mediator and target of inflammation, manifesting remodeling and resulting obstruction among its downstream effects. We also highlight the potential benefits of therapeutically targeting airway structural alterations. Since pathological tissue remodeling is likewise observed in other injury- and inflammation-prone tissues and organs, our discussion may have implications beyond asthma and lung disease.
哮喘是一种慢性气道疾病，长期以来被认为主要是一种炎症。因此，目前的治疗干预主要集中于解决炎症。然而，哮喘治疗的主要手段既不能完全改善肺功能，也不能预防疾病恶化，这表明其他因素参与其中。一个新兴的概念现在认为，哮喘的另一个主要病理特征气道重塑与哮喘发病机制中的炎症同样重要。与哮喘相关的结构变化包括破坏上皮完整性、上皮下纤维化、杯状细胞增生/化生、平滑肌肥大/增生和增强的血管分布。这些改变被假设为导致哮喘个体的气道高反应性、气道阻塞、气流受限和肺功能的进行性下降。因此，单独靶向炎症不足以提供最佳的临床益处。在这里，我们回顾了哮喘气道重塑，重点是气道上皮，这对维持健康的呼吸系统至关重要，也是对抗吸入刺激物的主要防御。在哮喘中，气道上皮是炎症的介质和靶标，在其下游效应中表现出重塑和导致的阻塞。我们还强调了治疗靶向气道结构改变的潜在益处。由于在其他易损伤和炎症的组织和器官中也观察到病理性组织重塑，因此我们的讨论可能具有哮喘和肺部疾病以外的意义。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
（Clin Sci (Lond). 2020 May 15;134(9):1063-1079. doi: 10.1042/CS20191309.）
（Clin Sci (Lond). 2020 May 15;134(9):1063-1079. doi: 10.1042/CS20191309.）
Bidirectional interaction of airway epithelial remodeling and inflammation in asthma
Asoka Banno, Aravind T Reddy , Sowmya P Lakshmi , Raju C Reddy
Abstract
Asthma is a chronic disease of the airways that has long been viewed predominately as an inflammatory condition. Accordingly, current therapeutic interventions focus primarily on resolving inflammation. However, the mainstay of asthma therapy neither fully improves lung function nor prevents disease exacerbations, suggesting involvement of other factors. An emerging concept now holds that airway remodeling, another major pathological feature of asthma, is as important as inflammation in asthma pathogenesis. Structural changes associated with asthma include disrupted epithelial integrity, subepithelial fibrosis, goblet cell hyperplasia/metaplasia, smooth muscle hypertrophy/hyperplasia, and enhanced vascularity. These alterations are hypothesized to contribute to airway hyperresponsiveness, airway obstruction, airflow limitation, and progressive decline of lung function in asthmatic individuals. Consequently, targeting inflammation alone does not suffice to provide optimal clinical benefits. Here we review asthmatic airway remodeling, focusing on airway epithelium, which is critical to maintaining a healthy respiratory system, and is the primary defense against inhaled irritants. In asthma, airway epithelium is both a mediator and target of inflammation, manifesting remodeling and resulting obstruction among its downstream effects. We also highlight the potential benefits of therapeutically targeting airway structural alterations. Since pathological tissue remodeling is likewise observed in other injury- and inflammation-prone tissues and organs, our discussion may have implications beyond asthma and lung disease.
