Emory University Department of Pediatrics, Atlanta, Georgia, USA.
Curr Opin Allergy Clin Immunol. 2012 Apr;12(2):193-201. doi: 10.1097/ACI.0b013e32835090ac.
Children with severe asthma have a high degree of respiratory morbidity despite treatment with high doses of inhaled corticosteroids and are therefore very difficult to treat. This review will discuss phenotypic and pathogenic aspects of severe asthma in childhood, as well as remaining knowledge gaps.
As a group, children with severe asthma have a number of distinct phenotypic features compared with children with mild-to-moderate asthma. Clinically, children with severe asthma are differentiated by greater allergic sensitization, increased exhaled nitric oxide, and significant airflow limitation and air trapping that worsens as a function of age. These findings are accompanied by structural airway changes and increased and dysregulated airway inflammation and oxidant stress which may explain the differential nature of corticosteroid responsiveness in this population. Because children with severe asthma themselves are a heterogeneous group, current efforts are focused on improved definition and sub-phenotyping of the disorder. Whereas the clinical relevance of phenotyping approaches in severe asthma is not yet clear, they may provide important insight into the mechanisms underlying the disorder.
Improved classification of severe asthma through unified definitions, careful phenotypic analyses, and mechanism-focused endotyping approaches may ultimately advance knowledge and personalized treatment.
尽管接受了高剂量吸入性皮质类固醇治疗，严重哮喘儿童仍存在高度的呼吸道发病率，因此治疗非常困难。这篇综述将讨论儿童严重哮喘的表型和发病机制方面，以及尚存的知识空白。
与轻度至中度哮喘儿童相比，严重哮喘儿童作为一个群体具有许多明显的表型特征。从临床角度来看，严重哮喘儿童的特点是过敏反应更严重、呼出气一氧化氮增加，以及随着年龄的增长而恶化的明显气流受限和空气滞留。这些发现伴随着气道结构的变化，以及增加和失调的气道炎症和氧化应激，这可能解释了该人群中皮质类固醇反应性的不同性质。由于严重哮喘儿童本身就是一个异质群体，目前的努力集中在改善该疾病的定义和亚表型。虽然表型方法在严重哮喘中的临床相关性尚不清楚，但它们可能为该疾病的发病机制提供重要的见解。
通过统一的定义、仔细的表型分析以及以机制为重点的终末分型方法来改善严重哮喘的分类，最终可能会促进知识的发展和个体化治疗。
