Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.
Research Centre, Sainte-Justine University Health Centre, Montreal, Quebec, Canada.
Pediatr Pulmonol. 2019 Apr;54(4):378-385. doi: 10.1002/ppul.24247. Epub 2019 Jan 15.
We documented inter-individual variability in the response to acute asthma therapy in children, attributed in part to five clinical factors (oxygen saturation, asthma severity score, virus detection, fever, symptoms between exacerbations; DOORWAY study). The contribution of genetic determinants of failure of acute asthma management have not been elucidated.
We aim to determine single nucleotide polymorphisms (SNP) associated with emergency department (ED) management failure in children.
A prospective cohort of 591 Caucasian children aged 1-17 years with moderate-to-severe asthma managed with standardized protocol were included. We examined 53 SNPs previously associated with asthma development, phenotypes, or bronchodilator or corticosteroids response. Associations between SNPs and management failure (hospitalization, active asthma management ≥8 h in ED, or a return visit within 72 h for one of two previous criteria) were examined using logistic regression, adjusting for the five clinical predictors of management failure.
Four-hundred ninety-one subjects had complete clinical data and usable DNA samples. While controlling for clinical determinants, rs295137 in SPATS2L (OR = 1.77, 95%CI: 1.17, 2.68) was significantly associated with increased odds of ED management failure. Two SNPs in IL33 were associated with decreased odds of ED management failure: rs7037276 (OR = 0.55, 95%CI: 0.33, 0.90), and rs1342326 (OR = 0.52, 95%CI: 0.32, 0.86). The addition of these three SNPs to the clinical predictors significantly improved the model's predictive performance (P < 0.0004).
Three SNPs were significantly associated with ED management failure in addition to clinical predictors, contributing to inter-individual variability. None has been previously associated with treatment response to acute asthma management.
我们记录了儿童急性哮喘治疗反应的个体间差异，部分归因于五个临床因素（氧饱和度、哮喘严重程度评分、病毒检测、发热、缓解期症状；DOORWAY 研究）。急性哮喘管理失败的遗传决定因素的贡献尚未阐明。
我们旨在确定与儿童急诊管理失败相关的单核苷酸多态性（SNP）。
纳入了一项前瞻性队列研究，共纳入 591 名 1-17 岁的白种人中重度哮喘患儿，采用标准化方案进行管理。我们检测了与哮喘发病、表型或支气管扩张剂或皮质激素反应相关的 53 个 SNP。使用逻辑回归分析 SNP 与管理失败（住院、ED 中主动管理≥8 小时或因前两个标准中的一个在 72 小时内再次就诊）之间的关系，调整管理失败的五个临床预测因子。
491 名患者具有完整的临床数据和可用的 DNA 样本。在控制临床决定因素的情况下，SPATS2L 中的 rs295137（OR=1.77，95%CI：1.17，2.68）与 ED 管理失败的几率增加显著相关。IL33 中的两个 SNP 与 ED 管理失败的几率降低相关：rs7037276（OR=0.55，95%CI：0.33，0.90）和 rs1342326（OR=0.52，95%CI：0.32，0.86）。将这三个 SNP 添加到临床预测因子中，显著提高了模型的预测性能（P<0.0004）。
除了临床预测因子外，三个 SNP 与 ED 管理失败显著相关，导致个体间差异。以前没有一个 SNP 与急性哮喘管理的治疗反应相关。
