Tiotropium in asthma – perspectives for the primary care physician

Asthma is a heterogeneous disease characterized by airway inflammation resulting from complex interactions between multiple hosts as well as environmental factors. As a chronic respiratory condition, asthma exerts a significant impact on patients and the healthcare system. Per the Global Initiative for Asthma (GINA), inhaled corticosteroids (ICS) with/without long-acting beta₂-agonists (LABAs) should be used as the preferred controllers for the management of asthma. Despite a range of therapeutic options, many patients with asthma remain uncontrolled, resulting in an increased risk of hospitalization and emergency room visits and a worsened quality of life. Tiotropium (Spiriva®, Boehringer Ingelheim Pharmaceuticals, Inc; 1.25 µg, two puffs, once daily), delivered via the Respimat® inhaler (Boehringer Ingelheim Pharmaceuticals, Inc.), was the first long-acting muscarinic antagonist to be approved as an add-on maintenance treatment option for patients with asthma aged ≥6 years at GINA steps 4 and 5. By binding to the muscarinic receptors M1 and M3 in the bronchial airways, tiotropium antagonizes the action of acetylcholine, leading to smooth muscle relaxation and reduced mucus secretion. The efficacy and safety of tiotropium add-on to ICS±LABA maintenance treatment have been evaluated in randomized controlled trials (RCTs) involving patients with a range of asthma severities (mild, moderate, and severe) and across age groups (children, adolescents, and adults). Add-on tiotropium was found to be well tolerated and efficacious in all RCTs. Moreover, the findings from real-world studies complement results from RCTs, showing beneficial effects of tiotropium in reducing exacerbations, hospitalization, emergency room visits, and asthma worsening. In this review article, we discuss the pathophysiology of asthma and the role of tiotropium in the management of asthma from the perspective of a primary care physician.

哮喘是一种异质性疾病，以多种宿主与环境因素复杂相互作用引发的气道炎症为特征。作为一种慢性呼吸道疾病，哮喘对患者及医疗保健系统均造成显著影响。根据全球哮喘防治创议（Global Initiative for Asthma, GINA）的指南，吸入性糖皮质激素（inhaled corticosteroids, ICS）联合或不联合长效β₂受体激动剂（long-acting beta₂-agonists, LABAs）应作为哮喘管理的首选控制药物。尽管存在多种治疗选择，仍有大量哮喘患者的病情未能得到有效控制，这会增加其住院、急诊就诊风险，并降低生活质量。噻托溴铵（思力华®，勃林格殷格翰制药公司；1.25 μg，2吸，每日1次）通过Respimat®吸入器（勃林格殷格翰制药公司）给药，是首个被批准用于GINA分级4级和5级、年龄≥6岁哮喘患者的附加维持治疗方案的长效毒蕈碱受体拮抗剂（long-acting muscarinic antagonist）。噻托溴铵可通过结合支气管气道内的毒蕈碱受体M1和M3，拮抗乙酰胆碱的作用，进而使平滑肌松弛并减少黏液分泌。针对在ICS±LABA维持治疗基础上加用噻托溴铵的疗效与安全性，已有多项纳入不同严重程度（轻度、中度、重度）哮喘患者及各年龄段（儿童、青少年、成人）人群的随机对照试验（randomized controlled trials, RCTs）进行了评估。所有上述随机对照试验均发现，附加噻托溴铵治疗具有良好的耐受性与疗效。此外，真实世界研究的结果也补充了随机对照试验的结论，证实噻托溴铵可减少哮喘急性加重、住院、急诊就诊及病情恶化。在本篇综述文章中，我们将从初级保健医师的视角，探讨哮喘的病理生理学机制，以及噻托溴铵在哮喘管理中的作用。