Pulmonary Cell Research and Pneumology, Department Biomedicine and Internal Medicine, University Hospital Basel, 4031, Basel, Switzerland,
Drugs. 2015 Jan;75(1):1-8. doi: 10.1007/s40265-014-0319-0.
Lung tissue remodelling in chronic inflammatory lung diseases has long been regarded as a follow-up event to inflammation. Recent studies have indicated that, although airway and lung tissue remodelling is often independent of inflammation, it precedes or causes inflammation. None of the available therapies has a significant effect on airway and lung tissue remodelling in asthma, bronchiectasis, fibrosis and chronic obstructive pulmonary disease (COPD). The goal of stopping or reversing lung tissue remodelling is difficult, as the term summarizes the net effect of independent events, including (1) cell proliferation, (2) cell volume increase, (3) cell migration, (4) modified deposition and metabolism of specific extracellular matrix components, and (5) local action of infiltrated inflammatory cells. The extracellular matrix of the lung has a very high turnover, and thus small changes may accumulate to significant structural pathologies, which seem to be irreversible. The most important question is 'why are pathological changes of the lung structure irreversible and resistant to drugs?' Many drugs have the potential to reduce remodelling mechanisms in vitro but fail in clinical trials. New evidence suggests that muscarinic receptor inhibitors have the potential to improve lung function through modifying tissue remodelling. However, the role of muscarinic receptors in lung remodelling, especially their supportive role for other remodelling driving factors, needs to be further investigated. The focus of this review is the role of muscarinic receptors in lung tissue remodelling as it has been reported in the human lung.
慢性炎症性肺疾病中的肺组织重塑长期以来一直被认为是炎症的后续事件。最近的研究表明,尽管气道和肺组织重塑通常与炎症无关,但它先于或引起炎症。在哮喘、支气管扩张、纤维化和慢性阻塞性肺疾病(COPD)中,现有的治疗方法都不能显著影响气道和肺组织重塑。阻止或逆转肺组织重塑的目标是困难的,因为这个术语总结了独立事件的净效应,包括(1)细胞增殖,(2)细胞体积增加,(3)细胞迁移,(4)特定细胞外基质成分的沉积和代谢的改变,以及(5)浸润的炎症细胞的局部作用。肺的细胞外基质具有非常高的周转率,因此微小的变化可能累积到显著的结构病理学,这似乎是不可逆转的。最重要的问题是“为什么肺结构的病理性变化是不可逆转的,对药物有抗性?”许多药物在体外有潜力减少重塑机制,但在临床试验中失败。新的证据表明,毒蕈碱受体抑制剂通过改变组织重塑有潜力改善肺功能。然而,毒蕈碱受体在肺重塑中的作用,特别是它们对其他重塑驱动因素的支持作用,需要进一步研究。这篇综述的重点是毒蕈碱受体在肺组织重塑中的作用,因为它在人类肺中已经有报道。