Cook James, Saglani Sejal
aDepartment of Respiratory Paediatrics, Royal Brompton Hospital bRespiratory Sciences Division, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Curr Opin Pulm Med. 2016 Jan;22(1):25-31. doi: 10.1097/MCP.0000000000000223.
Exacerbations of asthma in children are most frequently precipitated by respiratory infections with a seasonal pattern. However, management takes little account of the underlying infective or other precipitant abnormality.
Interactions between environmental triggers, the airway microbiome and innate immune responses are key determinants of exacerbations. Elevated innate cytokines interleukin (IL)-33 and IL-25, and abnormal molecular responses in the interferon pathway are associated with rhinoviral infections. Exacerbations caused by fungal allergens also induce IL-33, highlighting this as an attractive therapeutic target. An equal contribution of bacterial and viral infection during exacerbations, particularly in preschool children, has become increasingly apparent, but some organisms may be protective. Investigation of mechanisms underlying infection-related exacerbations especially in preschool children is needed.Progressive loss of lung function from exacerbations is most pronounced in children aged 6-11 years, and low FEV1 is now recognized as a key predictor for the development of chronic obstructive pulmonary disease and premature death. Although prevention of exacerbations is critical, suboptimal patient education, prescription and adherence to maintenance therapy, and a lack of predictive biomarkers, remain key unaddressed issues in children.
Precipitants and predictors of exacerbations, together with the child's age and clinical phenotype, need to be used to achieve individualized management in preference to the current uniform approach for all.
儿童哮喘急性发作最常见的诱因是季节性呼吸道感染。然而,治疗很少考虑潜在的感染性或其他诱发异常因素。
环境触发因素、气道微生物群和固有免疫反应之间的相互作用是急性发作的关键决定因素。固有细胞因子白细胞介素(IL)-33和IL-25升高,以及干扰素途径中的异常分子反应与鼻病毒感染有关。真菌过敏原引起的急性发作也会诱导IL-33,这使其成为一个有吸引力的治疗靶点。在急性发作期间,细菌和病毒感染的作用相当,尤其是在学龄前儿童中,这一点越来越明显,但有些微生物可能具有保护作用。需要对尤其是学龄前儿童感染相关急性发作的潜在机制进行研究。急性发作导致的肺功能进行性丧失在6至11岁儿童中最为明显,现在低FEV1被认为是慢性阻塞性肺疾病发展和过早死亡的关键预测指标。尽管预防急性发作至关重要,但患者教育不足、维持治疗的处方和依从性欠佳,以及缺乏预测性生物标志物,仍是儿童中尚未解决的关键问题。
急性发作的诱发因素和预测指标,以及儿童的年龄和临床表型,需要用于实现个体化管理,而不是目前对所有儿童采用的统一方法。