Abstract：
Recurrent wheezing in preschool children is heterogeneous and results from numerous genetic and environmental risk factors, which result in the same final clinical manifestation of acute episodes of wheezing but have distinct underlying mechanisms. Effective disease-modifying approaches, therefore, need to target the pathways driving the symptoms. We have good evidence to show that targeting airway eosinophilia alone in early-life preschool wheezing and using inhaled corticosteroids is not disease-modifying. Although airway remodelling develops early in preschool wheezing, the challenge is identifying suitable treatments for structural airway changes. There is increasing evidence for the role of lower airway bacterial infection contributing to wheeze episodes, but clinical trials investigating the impact of targeted antibiotic treatment on disease modification are needed. There is also increasing data supporting an association between lower airway neutrophilia and wheezing in a subgroup of preschool children, but direct causation and the role of neutrophil function remain unknown. Finally, there is encouraging preliminary data for the role of inactivated mixed bacterial lysates in children with non-allergic, infection-associated wheeze episodes, but the impact on longer-term outcomes and their mechanism of action is unknown. This review outlines a range of potential novel targets and approaches that may enable secondary prevention of asthma from preschool wheezing. In parallel, the potential for harm when interventions are introduced indiscriminately is highlighted. Some of the challenges that need to be addressed, including trial designs allowing tailored interventions, the need for non-invasive biomarkers for targeted interventions, and ensuring extended and long-term follow-up after intervention, are highlighted.
摘要：
学龄前儿童的反复喘息是异质性的，并且是由许多遗传和环境风险因素引起的。导致哮喘急性发作的最终临床表现相同，但具有不同的潜在机制。有效的疾病改善方法，因此,需要针对驱动症状的途径。我们有充分的证据表明，在早期学龄前哮喘中单独针对气道嗜酸性粒细胞增多症和使用吸入糖皮质激素并不能改善疾病。尽管气道重塑在学龄前哮喘早期发展，目前的挑战是为气道结构性改变确定合适的治疗方法.越来越多的证据表明下气道细菌感染在喘息发作中的作用。但需要进行临床试验,研究靶向抗生素治疗对疾病改变的影响.也有越来越多的数据支持下气道嗜中性粒细胞增多症和喘息之间的关联在学龄前儿童的一个亚组，但中性粒细胞功能的直接因果关系和作用尚不清楚。最后,关于灭活混合细菌裂解物在非过敏儿童中的作用，有令人鼓舞的初步数据，感染相关的喘息发作，但对长期结局的影响及其作用机制尚不清楚.这篇综述概述了一系列潜在的新目标和方法，这些目标和方法可能使学龄前哮喘的二级预防成为可能。并行,强调了不加选择地引入干预措施时的潜在危害。一些需要解决的挑战，包括允许定制干预的试验设计，需要非侵入性生物标志物进行有针对性的干预，并确保干预后的长期随访，被突出显示。
