Maglione Marco, Poeta Marco, Santamaria Francesca
Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Department of Pediatrics, Federico II University, Naples, Italy.
Front Pediatr. 2019 Jan 16;6:432. doi: 10.3389/fped.2018.00432. eCollection 2018.
Asthma is the most common chronic disease in children. As suggested by international guidelines, the main goals of asthma treatment are symptoms control and lung function preservation, through a stepwise and control-based approach. The first line therapy based on inhaled corticosteroids may fail to reach control in more than one third of patients, especially adolescents, and in these lung function and quality of life may progressively worsen. Treatment with omalizumab, the first anti-immunoglobulin E recombinant humanized monoclonal antibody, has been definitely approved in pediatric uncontrolled asthma. In this review, we discuss the mechanisms and potential roles of emerging therapies for pediatric severe asthma. Novel biologic drugs (i.e., dupilumab, mepolizumab, reslizumab, and benralizumab) seem to be promising in reducing annual exacerbation rates and steroid-use in glucocorticoid-dependent cases, but available data are few and limited to adolescents and adults. Evidences on the use of the muscarinic antagonist tiotropium as controller medication in pediatric settings are progressively growing, sustaining an application as asthma maintenance treatment in children aged >6 years and in preschool children with persistent asthmatic symptoms, but well powered trials are needed to confirm its safety and efficacy. New inhaled corticosteroids (i.e., ciclesonide and mometasone) are effective as once-daily controller therapy, but long-term studies in the different pediatric ages are needed to compare effectiveness and safety to usual treatments. At present, the role of macrolides in pediatric severe asthma is controversial and their administration is not recommended routinely, but may be considered in children with neutrophilic asthma for reducing daily oral steroids administration and improving lung function. Despite the availability of several novel therapeutic strategies for uncontrolled asthma, future trials targeted at specific pediatric age subgroups are needed to support evidences of safety and efficacy also in children.
哮喘是儿童最常见的慢性疾病。正如国际指南所建议的,哮喘治疗的主要目标是通过逐步和基于控制的方法来控制症状和保护肺功能。基于吸入性糖皮质激素的一线治疗在超过三分之一的患者中可能无法达到控制效果,尤其是青少年,在这些患者中,肺功能和生活质量可能会逐渐恶化。奥马珠单抗是第一种抗免疫球蛋白E重组人源化单克隆抗体,已被明确批准用于儿童难治性哮喘。在这篇综述中,我们讨论了针对儿童重度哮喘的新兴疗法的机制和潜在作用。新型生物药物(即度普利尤单抗、美泊利单抗、瑞利珠单抗和贝那利珠单抗)在降低糖皮质激素依赖病例的年度加重率和减少类固醇使用方面似乎很有前景,但现有数据很少,且仅限于青少年和成年人。关于使用毒蕈碱拮抗剂噻托溴铵作为儿童控制药物的证据越来越多,支持将其作为6岁以上儿童和有持续性哮喘症状的学龄前儿童的哮喘维持治疗,但需要有力的试验来证实其安全性和有效性。新型吸入性糖皮质激素(即环索奈德和莫米松)作为每日一次的控制疗法是有效的,但需要在不同儿童年龄组进行长期研究,以比较其与常规治疗的有效性和安全性。目前,大环内酯类药物在儿童重度哮喘中的作用存在争议,不建议常规使用,但对于嗜中性粒细胞性哮喘儿童,可考虑使用以减少每日口服类固醇的用量并改善肺功能。尽管有几种针对难治性哮喘的新型治疗策略,但仍需要针对特定儿童年龄亚组的未来试验,以支持在儿童中安全性和有效性的证据。