Buhl Roland, Hamelmann Eckard
Pulmonary Department, Johannes Gutenberg University Hospital Mainz, Mainz, Germany,
Children's Center Bethel, Evangelic Hospital Bethel, Department of Pediatrics, Bielefeld, Germany.
Ther Clin Risk Manag. 2019 Mar 14;15:473-485. doi: 10.2147/TCRM.S180890. eCollection 2019.
Despite major advances in therapeutic interventions and the availability of detailed treatment guidelines, a high proportion of patients with symptomatic asthma remain uncontrolled. Asthma management is largely guided by the Global Initiative for Asthma (GINA) strategy and is based on a backbone of inhaled corticosteroid (ICS) therapy with the use of additional therapies to achieve disease control. Inhaled long-acting bronchodilators alone and in combination are the preferred add-on treatment options. Although long-acting muscarinic antagonists (LAMAs) are a relatively recent addition to disease management recommendations for asthma, tiotropium has been extensively studied in a large clinical trial program. In Europe and the United States, tiotropium is approved for patients aged ≥6 years and uncontrolled on medium- to high-dose ICS/long-acting β-agonists at GINA Steps 4 and 5 with a history of exacerbations. Evidence supports the efficacy of tiotropium Respimat in adults in terms of lung function and asthma control, with a safety profile comparable with that of placebo across a range of asthma severities. Similarly, clinical trials in patients aged 1-17 years have shown improvements in lung function and trends toward improved asthma control. Furthermore, its efficacy makes tiotropium relatively easy to incorporate into routine clinical practice, irrespective of allergic status and without the need for patient phenotyping. Tiotropium is a cost-effective treatment that may offer an important alternative to other, more expensive add-on therapies. This review discusses the potential future position of LAMAs in clinical practice by considering the continuously evolving evidence. Prominence is given to tiotropium, the only LAMA supported by a structured clinical trial program in asthma to date, while also considering other recommended treatment options for patients with uncontrolled asthma. The importance of effective patient/caregiver-clinician communication and shared decision-making in enhancing treatment adherence is also highlighted.
尽管在治疗干预方面取得了重大进展，并且有详细的治疗指南可供参考，但仍有很大比例的症状性哮喘患者病情未得到控制。哮喘管理主要遵循全球哮喘防治创议（GINA）策略，其基础是吸入性糖皮质激素（ICS）治疗，并使用其他疗法来实现疾病控制。单独使用或联合使用吸入长效支气管扩张剂是首选的附加治疗方案。尽管长效毒蕈碱拮抗剂（LAMA）相对较新地被纳入哮喘疾病管理建议中，但噻托溴铵已在大型临床试验项目中得到广泛研究。在欧洲和美国，噻托溴铵被批准用于≥6岁、在GINA第4和第5步使用中高剂量ICS/长效β受体激动剂且病情仍未得到控制并有加重病史的患者。证据支持噻托溴铵Respimat在改善成人肺功能和控制哮喘方面的疗效，在一系列哮喘严重程度中其安全性与安慰剂相当。同样，在1 - 17岁患者中的临床试验显示肺功能有所改善，且有哮喘控制改善的趋势。此外，其疗效使噻托溴铵相对容易纳入常规临床实践，无论过敏状态如何，也无需对患者进行表型分析。噻托溴铵是一种具有成本效益的治疗方法，可能为其他更昂贵的附加疗法提供重要替代方案。本综述通过考虑不断演变的证据，讨论了LAMA在临床实践中未来可能的地位。重点介绍了噻托溴铵，它是迄今为止哮喘领域唯一有结构化临床试验项目支持的LAMA，同时也考虑了其他针对病情未得到控制的哮喘患者的推荐治疗方案。还强调了有效的患者/护理人员与临床医生沟通以及共同决策在提高治疗依从性方面的重要性。
