Department of Allergy and Clinical Immunology, Ajou University Medical Center, Suwon, South Korea.
Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh city, Ho Chi Minh city, Vietnam.
Expert Rev Respir Med. 2019 Dec;13(12):1169-1178. doi: 10.1080/17476348.2019.1670640. Epub 2019 Sep 26.
: Asthma is a chronic inflammatory disease of the airways with a large heterogeneity of clinical phenotypes. There has been increasing interest regarding the role of cysteinyl leukotriene (LT) and leukotriene receptor antagonists (LTRA) in asthma treatment.: This review summarized the data (published in PubMed during 1984-2019) regarding LTRA treatment in asthma and LTs-related airway inflammation mechanisms. Involvement of LTs C/D/E has been demonstrated in the several aspects of airway inflammation and remodeling. Novel pathways related to LTE, the most potent mediator, and its respective receptors have recently been studied. Antagonists against cysteinyl leukotriene receptor (CysLTR) type 1, including montelukast, pranlukast and zafirlukast, have been widely prescribed in clinical practices; however, some clinical trials have shown insignificant responses to LTRAs in adult asthmatics, while some phenotypes of adult asthma showed more favorable responses to LTRAs including aspirin-exacerbated respiratory disease, elderly asthma, asthma associated with smoking, obesity and allergic rhinitis.: Further investigations are needed to understand the role of LTs in airway inflammation and remodeling of the asthmatic airways. There is a lack of biomarkers to predict responsiveness to LTRA, especially in adult asthmatics. Besides CysLTR1 antagonists, targets aiming other LT pathways should be considered.
哮喘是一种气道的慢性炎症性疾病,具有很大的临床表型异质性。人们对半胱氨酰白三烯(LT)和白三烯受体拮抗剂(LTRA)在哮喘治疗中的作用越来越感兴趣。本文总结了(1984 年至 2019 年期间在 PubMed 上发表的)关于 LTRA 治疗哮喘和 LT 相关气道炎症机制的数据。LTs C/D/E 参与了气道炎症和重塑的几个方面。最近研究了与 LTE(最强的介质)及其各自受体相关的新途径。针对半胱氨酰白三烯受体(CysLTR)类型 1 的拮抗剂,包括孟鲁司特、普仑司特和扎鲁司特,已广泛应用于临床实践中;然而,一些临床试验表明 LTRAs 对成年哮喘患者的反应不显著,而成年哮喘的一些表型对 LTRAs 反应更为有利,包括阿司匹林加重的呼吸道疾病、老年哮喘、与吸烟相关的哮喘、肥胖和过敏性鼻炎。需要进一步研究以了解 LT 在哮喘气道炎症和重塑中的作用。目前缺乏预测 LTRA 反应性的生物标志物,尤其是在成年哮喘患者中。除了 CysLTR1 拮抗剂外,还应考虑针对其他 LT 途径的靶点。