Selby Louise, Saglani Sejal
Department of Respiratory Paediatrics, Royal Brompton Hospital.
Department of Inflammation Repair and Development, National Heart and Lung Institute, Imperial College London, London, UK.
Curr Opin Allergy Clin Immunol. 2019 Apr;19(2):132-140. doi: 10.1097/ACI.0000000000000521.
Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring and a detailed multidisciplinary team assessment to identify modifiable factors contributing to poor control is needed prior to considering therapy escalation. Pathophysiological phenotyping in those with true severe therapy-resistant asthma (STRA) and the current array of add-on therapies will be discussed.
Adherence monitoring using electronic devices has shown that only 20-30% of children with PSA have STRA and need additional therapies. Omalizumab and mepolizumab are licensed for children with STRA aged 6 years and older. Although robust safety and efficacy data, with reduced exacerbations, are available for omalizumab, biomarkers predicting response to treatment are lacking. Paediatric safety data are available for mepolizumab, but efficacy data are unknown for those aged 6-11 years and minimal for those 12 years and older. A sub-group of children with STRA have neutrophilia, but the clinical significance and contribution to disease severity remains uncertain.
Most children with PSA have steroid sensitive disease which improves with adherence to maintenance inhaled corticosteroids. Add-on therapies are only needed for the minority with STRA. Paediatric efficacy data of novel biologics and biomarkers that identify the optimal add-on for each child are lacking. If we are to progress toward individualized therapy for STRA, pragmatic clinical trials of biologics in accurately phenotyped children are needed.
尽管接受了最大程度的维持治疗，但哮喘控制不佳的儿童患有难治性重度哮喘（PSA）。在考虑升级治疗之前，需要采取逐步的方法，包括客观的依从性监测和详细的多学科团队评估，以确定导致控制不佳的可改变因素。将讨论真正的重度难治性哮喘（STRA）患者的病理生理表型以及当前一系列附加疗法。
使用电子设备进行的依从性监测表明，只有20%-30%的PSA儿童患有STRA且需要额外治疗。奥马珠单抗和美泊利珠单抗已被批准用于6岁及以上的STRA儿童。虽然奥马珠单抗有可靠的安全性和有效性数据，且能减少病情加重，但缺乏预测治疗反应的生物标志物。美泊利珠单抗有儿科安全性数据，但6-11岁儿童的有效性数据未知，12岁及以上儿童的有效性数据极少。一小部分STRA儿童存在嗜中性粒细胞增多，但临床意义及其对疾病严重程度的影响仍不确定。
大多数PSA儿童患有对类固醇敏感的疾病，通过坚持使用维持性吸入糖皮质激素病情会改善。只有少数STRA儿童需要附加疗法。新型生物制剂的儿科有效性数据以及能为每个儿童确定最佳附加疗法的生物标志物均缺乏。如果我们要朝着STRA的个体化治疗取得进展，就需要在准确表型的儿童中进行生物制剂的务实临床试验。
