Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Parma, Italy.
Division of Respiratory Medicine, University Hospital "Policlinico Tor Vergata", Rome, Italy.
Int J Chron Obstruct Pulmon Dis. 2021 Feb 12;16:257-279. doi: 10.2147/COPD.S285867. eCollection 2021.
Long-acting muscarinic receptor antagonists (LAMAs) are the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD); furthermore, tiotropium is approved as add-on therapy in severe asthmatic patients. Accumulating evidence suggests that LAMAs may modulate airway contractility and airway hyperresponsiveness not only by blocking muscarinic acetylcholine receptors (mAchRs) expressed on airway smooth muscle but also via anti-inflammatory mechanisms by blocking mAchRs expressed on inflammatory cells, submucosal glands, and epithelial cells. The aim of this systematic review, performed according to the PRISMA-P guidelines, was to provide a synthesis of the literature on the anti-inflammatory impact of muscarinic receptor antagonists in the airways. Most of the current evidence originates from studies on tiotropium, that demonstrated a reduction in synthesis and release of cytokines and chemokines, as well as the number of total and differential inflammatory cells, induced by different pro-inflammatory stimuli. Conversely, few data are currently available for aclidinium and glycopyrronium, whereas no studies on the potential anti-inflammatory effect of umeclidinium have been reported. Overall, a large body of evidence supports the beneficial impact of tiotropium against airway inflammation. Further well-designed randomized controlled trials are needed to better elucidate the anti-inflammatory mechanisms leading to the protective effect of LAMAs against exacerbations via identifying suitable biomarkers.
长效毒蕈碱受体拮抗剂（LAMA）是治疗慢性阻塞性肺疾病（COPD）的基石；此外，噻托溴铵被批准用于严重哮喘患者的附加治疗。越来越多的证据表明，LAMA 不仅通过阻断气道平滑肌上表达的毒蕈碱乙酰胆碱受体（mAchR），还通过阻断炎症细胞、黏膜下腺和上皮细胞上表达的 mAchR 来调节气道收缩性和气道高反应性，具有抗炎机制。本系统评价按照 PRISMA-P 指南进行，旨在综合文献中关于毒蕈碱受体拮抗剂在气道中的抗炎作用。目前大部分证据来源于噻托溴铵的研究，这些研究表明，噻托溴铵可减少不同促炎刺激物诱导的细胞因子和趋化因子的合成和释放，以及总炎性细胞和差异炎性细胞的数量。相反，目前关于阿地溴铵和格隆溴铵的数据较少，而关于乌美溴铵潜在抗炎作用的研究尚未报道。总的来说，大量证据支持噻托溴铵对气道炎症的有益影响。需要进一步设计良好的随机对照试验，以更好地阐明导致 LAMA 通过识别合适的生物标志物对加重期具有保护作用的抗炎机制。
