Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogota, Colombia.
Department of Pediatric Pulmonology and Pediatric Critical Care Medicine, School of Medicine, Universidad El Bosque, Bogota, Colombia.
Pediatr Pulmonol. 2020 Jun;55(6):1320-1331. doi: 10.1002/ppul.24782. Epub 2020 Apr 16.
There has been no systematic review of studies aimed to predict differential responses to medication regimens for asthma controller therapies in pediatric patients. The aim of the present study was to summarize those identifying biomarkers for the different asthma controller therapies.
Studies published by June 2019 that report phenotypic or genotypic characteristics or biomarkers that could potentially serve as response predictors to asthma controller therapies in pediatric patients were included. The quality of studies was assessed using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale tool.
Of 385 trials identified, 30 studies were included. Children with asthma and a positive family history of asthma, with more severe disease, of the white race, with allergy biomarkers, nonobese, with lower lung function, high bronchial hyperresponsiveness to methacholine, or having variants in the FCER2 and CRHR1 gene respond better to inhaled corticosteroids (ICS). Younger age (<10 years), short disease duration (<4 years), high cotinine and urinary leukotriene E4 (LTE4) levels, and 5/5 ALOX5 were associated with a better response to leukotriene receptor antagonist (LTRA). For patients that remain symptomatic, white Hispanics were more likely to respond to LTRA, blacks to ICS, white non-Hispanics to LTRA or LABA, and children without a history of eczema, regardless of race or ethnicity to LABA set-up therapy. In severe persistent asthma, those with atopy and body mass index greater than or equal 25 were more likely to benefit from omalizumab.
Several phenotypic characteristics, biomarkers, or pharmacogenomics markers could be useful for predicting the best drug for asthma treatment.
目前尚未对旨在预测儿科患者哮喘控制药物治疗的差异化反应的研究进行系统评价。本研究旨在总结那些可用于预测不同哮喘控制治疗的生物标志物。
纳入了截至 2019 年 6 月发表的报告了表型或基因型特征或生物标志物的研究，这些特征或生物标志物可能作为儿科患者哮喘控制治疗的反应预测指标。使用 Cochrane 偏倚风险工具和纽卡斯尔-渥太华量表工具评估研究质量。
在确定的 385 项试验中，有 30 项研究入选。具有哮喘阳性家族史、疾病更严重、白种人、过敏生物标志物、非肥胖、肺功能较低、对乙酰甲胆碱的支气管高反应性较高、或 FCER2 和 CRHR1 基因变异的哮喘患儿对吸入性皮质类固醇（ICS）的反应更好。年龄较小（<10 岁）、疾病持续时间较短（<4 年）、较高的可替宁和尿白三烯 E4（LTE4）水平、以及 5/5 ALOX5 与对白三烯受体拮抗剂（LTRA）的更好反应相关。对于仍然有症状的患者，白西班牙裔人对 LTRA 的反应更可能，黑人对 ICS，白种非西班牙裔人对 LTRA 或 LABA，以及无论种族或族裔如何，没有特应性皮炎史的儿童对 LABA 治疗方案的反应更可能。在严重持续性哮喘中，过敏和体重指数大于或等于 25 的患者更可能从奥马珠单抗中获益。
一些表型特征、生物标志物或药物基因组学标记可能有助于预测哮喘治疗的最佳药物。
