Non-neuronal cholinergic system (NNCS) contributes to various inflammatory airway diseases. However, the role of NNCS in severe asthma (SA) remains largely unexplored. To explore airway NNCS in SA. In this prospective cohort study based on the Australasian Severe Asthma Network in a real-world setting, patients with SA (n = 52) and non-SA (n = 104) underwent clinical assessment and sputum induction. The messenger RNA (mRNA) levels of NNCS components and proinflammatory cytokines in the sputum were detected using real-time quantitative polymerase chain reaction, and the concentrations of acetylcholine (Ach)-related metabolites were evaluated using liquid chromatography coupled with tandem mass spectrometry. Asthma exacerbations were prospectively investigated during the next 12 months. The association between NNCS and future asthma exacerbations was also analyzed. Patients with SA were less controlled and had worse airway obstruction, a lower bronchodilator response, higher doses of inhaled corticosteroids, and more add-on treatments. The sputum mRNA levels of NNCS components, such as muscarinic receptors -, and ; proinflammatory cytokines; and Ach concentration in the SA group were significantly higher than those in the non-SA group. Furthermore, most NNCS components positively correlated with non-type (T) 2 inflammatory profiles, such as sputum neutrophils, , and . In addition, the mRNA levels of sputum , and were independently associated with an increased risk of moderate-to-severe asthma exacerbations. This study indicated that the NNCS was significantly activated in SA, leading to elevated Ach and was associated with clinical features, non-T2 inflammation, and future exacerbations of asthma, highlighting the potential role of the NNCS in the pathogenesis of SA. ChiCTR-OOC-16009529 ().

中文翻译：

---

激活的非神经元胆碱能系统与严重哮喘的非 2 型炎症和恶化相关

非神经元胆碱能系统（NNCS）导致各种炎症性气道疾病。然而，NNCS 在严重哮喘 (SA) 中的作用在很大程度上仍未被探索。探索 SA 的气道 NNCS。在这项基于澳大利亚严重哮喘网络的现实世界中的前瞻性队列研究中，SA 患者 (n = 52) 和非 SA 患者 (n = 104) 接受了临床评估和痰诱导。采用实时定量聚合酶链反应检测痰中NNCS成分和促炎细胞因子的信使RNA（mRNA）水平，并采用液相色谱-串联质谱法评估乙酰胆碱（Ach）相关代谢物的浓度。在接下来的 12 个月内对哮喘恶化情况进行了前瞻性调查。还分析了 NNCS 与未来哮喘恶化之间的关联。 SA 患者控制较差，气道阻塞更严重，支气管扩张剂反应较低，吸入皮质类固醇剂量较高，附加治疗较多。 NNCS 成分（例如毒蕈碱受体）的痰 mRNA 水平 - 和 ；促炎细胞因子； SA组中Ach浓度显着高于非SA组。此外，大多数 NNCS 成分与非 (T) 2 型炎症特征呈正相关，例如痰中性粒细胞、和。此外，痰中 、 和 的 mRNA 水平与中度至重度哮喘恶化的风险增加独立相关。这项研究表明，NNCS 在 SA 中显着激活，导致 Ach 升高，并与临床特征、非 T2 炎症和未来哮喘恶化相关，强调了 NNCS 在 SA 发病机制中的潜在作用。 ChiCTR-OOC-16009529 ()。