Departments of Anesthesiology & Perioperative Medicine Mayo Clinic, Rochester, MN, USA.
Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
Expert Opin Ther Targets. 2023 Jan;27(1):19-29. doi: 10.1080/14728222.2023.2177533. Epub 2023 Feb 13.
Asthma is characterized by enhanced airway contractility and remodeling where airway smooth muscle (ASM) plays a key role, modulated by inflammation. Understanding the mechanisms by which ASM contributes to these features of asthma is essential for the development of novel asthma therapies.
Inflammation in asthma contributes to a multitude of changes within ASM including enhanced airway contractility, proliferation, and fibrosis. Altered intracellular calcium ([Ca]) regulation or Ca sensitization contributes to airway hyperreactivity. Increased airway wall thickness from ASM proliferation and fibrosis contributes to structural changes seen with asthma.
ASM plays a significant role in multiple features of asthma. Increased ASM contractility contributes to hyperresponsiveness, while altered ASM proliferation and extracellular matrix production promote airway remodeling both influenced by inflammation of asthma and conversely even influencing the local inflammatory milieu. While standard therapies such as corticosteroids or biologics target inflammation, cytokines, or their receptors to alleviate asthma symptoms, these approaches do not address the underlying contribution of ASM to hyperresponsiveness and particularly remodeling. Therefore, novel therapies for asthma need to target abnormal contractility mechanisms in ASM and/or the contribution of ASM to remodeling, particularly in asthmatics resistant to current therapies.
哮喘的特征是气道收缩性增强和重塑，其中气道平滑肌（ASM）起着关键作用，受炎症调节。了解 ASM 如何促成哮喘的这些特征对于开发新型哮喘疗法至关重要。
哮喘中的炎症导致 ASM 发生多种变化，包括气道收缩性增强、增殖和纤维化。细胞内钙（[Ca]）调节或 Ca 敏化的改变导致气道高反应性。ASM 增殖和纤维化导致气道壁厚度增加，从而导致哮喘中出现的结构变化。
ASM 在哮喘的多种特征中起着重要作用。增加的 ASM 收缩性导致高反应性，而 ASM 增殖和细胞外基质产生的改变则促进气道重塑，这两者均受哮喘炎症的影响，反过来又影响局部炎症环境。虽然标准疗法如皮质类固醇或生物制剂针对炎症、细胞因子或其受体来缓解哮喘症状，但这些方法不能解决 ASM 对高反应性，特别是对重塑的潜在贡献。因此，需要针对 ASM 异常收缩机制和/或 ASM 对重塑的贡献，为哮喘开发新型疗法，特别是针对对现有疗法有抗性的哮喘患者。
