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生物制剂在儿童和青少年哮喘治疗中的应用

Biologics in the treatment of asthma in children and adolescents.

作者信息

Bacharier Leonard B, Jackson Daniel J

机构信息

Department of Pediatrics, Monroe Carell Jr Children's Hospital at Vanderbilt University Medical Center, Nashville, Tenn.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.

出版信息

J Allergy Clin Immunol. 2023 Mar;151(3):581-589. doi: 10.1016/j.jaci.2023.01.002. Epub 2023 Jan 24.

Abstract

Severe asthma in childhood confers substantial patient- and society-level burdens. Although biologics have been available for the management in adults and adolescents for nearly 20 years, research on the efficacy and safety of biologics in children and adolescents has lagged. Fortunately, more recent research specifically in children has provided an evidence base for biologic use in this age group. Most children with severe asthma demonstrate a type 2 inflammatory phenotype, the primary target of currently approved biologics. Three biologics, omalizumab, mepolizumab, and duplilumab, are Food and Drug Administration-approved for children as young as 6 years, whereas benralizumab and tezepelumab are approved for adolescents older than 12 years. All these agents reduce the rates of severe asthma exacerbations, whereas their effects on pulmonary function vary across agents. Safety profiles are reassuring, although additional long-term safety data in children are still needed. The choice of a biologic agent follows a careful assessment of other factors that contribute to uncontrolled asthma and includes biomarkers of blood eosinophils, fractional exhaled nitric oxide, allergic sensitization, and IgE levels. This review focuses on the underlying pathophysiology of childhood asthma, an approach to phenotyping patients, and the efficacy, safety, and use of biologics in children and adolescents with severe asthma.

摘要

儿童重度哮喘给患者和社会带来了沉重负担。尽管生物制剂已用于成人和青少年哮喘治疗近20年,但关于生物制剂在儿童和青少年中的疗效和安全性研究却滞后了。幸运的是,最近专门针对儿童的研究为该年龄组使用生物制剂提供了证据基础。大多数重度哮喘儿童表现出2型炎症表型,这是目前获批生物制剂的主要靶点。三种生物制剂,即奥马珠单抗、美泊利单抗和度普利尤单抗,已获美国食品药品监督管理局批准用于6岁及以上儿童,而贝那利珠单抗和tezepelumab则获批用于12岁以上青少年。所有这些药物均可降低重度哮喘发作率,但其对肺功能的影响因药物而异。尽管仍需要更多儿童长期安全性数据,但安全性概况令人放心。生物制剂的选择需仔细评估导致哮喘控制不佳的其他因素,包括血液嗜酸性粒细胞生物标志物、呼出一氧化氮分数、过敏致敏和IgE水平。本综述重点关注儿童哮喘的潜在病理生理学、患者表型分析方法以及生物制剂在儿童和青少年重度哮喘中的疗效、安全性和应用。

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