Division of Cardiac Critical Care Medicine, Children's National Hospital, Washington, DC, USA.
Department of Genomics and Precision Medicine, George Washington University, Washington, DC, USA.
Clin Infect Dis. 2021 Nov 2;73(9):e2665-e2672. doi: 10.1093/cid/ciaa1700.
Although bronchiolitis contributes to substantial acute (eg, intensive care use) and chronic (eg, recurrent wheeze) morbidities in young children, the pathobiology remains uncertain. We examined the associations of serum soluble receptor for advanced glycation end products (sRAGE) with acute and chronic morbidities of bronchiolitis including recurrent wheeze.
A multicenter, multiyear, cohort study of infants hospitalized for bronchiolitis was analyzed. We measured the serum sRAGE level at hospitalization and its association with intensive care use (use of mechanical ventilation and/or admission to the intensive care unit) and development of recurrent wheeze by age 3 years. We performed causal mediation analysis to estimate indirect (mediation) and direct effects of sRAGE on recurrent wheeze.
In 886 infants with bronchiolitis, the median age was 2.9 months. Overall, 15% underwent intensive care and 32% developed recurrent wheeze. In multivariable modeling adjusting for 11 confounders, a higher presenting sRAGE level was associated with lower risk of intensive care (odds ratio for each 1-log increment, 0.39; 95% confidence interval [CI], .16 -.91; P = .03) and significantly lower rate of recurrent wheeze (hazard ratio [HR], 0.58; 95% CI, .36 -.94; P = .03). In mediation analysis, the direct effect was significant (HR, 0.60; 95% CI, .37 -.97; P = .04), while the indirect effect was not (P = .30).
Serum sRAGE levels were inversely associated with acute and chronic morbidities of bronchiolitis. The effect of sRAGE on development of recurrent wheeze is potentially driven through pathways other than acute severity of bronchiolitis.
毛细支气管炎可导致幼儿出现大量急性（例如，重症监护使用）和慢性（例如，反复喘息）疾病，但发病机制仍不确定。我们研究了血清晚期糖基化终产物可溶性受体（sRAGE）与毛细支气管炎的急性和慢性疾病的关联，包括反复喘息。
分析了一项多中心、多年的毛细支气管炎住院患儿队列研究。我们在住院时测量了血清 sRAGE 水平，并将其与使用机械通气和/或入住重症监护病房的重症监护使用以及 3 岁时反复喘息的发展进行了关联。我们进行了因果中介分析，以估计 sRAGE 对反复喘息的间接（中介）和直接影响。
在 886 例毛细支气管炎患儿中，中位年龄为 2.9 个月。总体而言，15%的患儿接受了重症监护，32%的患儿出现反复喘息。在调整了 11 个混杂因素的多变量模型中，较高的 sRAGE 水平与较低的重症监护风险相关（每增加 1 个对数增量的比值比为 0.39；95%置信区间 [CI]，0.16-0.91；P = 0.03），且反复喘息的发生率显著降低（风险比 [HR]，0.58；95% CI，0.36-0.94；P = 0.03）。在中介分析中，直接效应显著（HR，0.60；95% CI，0.37-0.97；P = 0.04），而间接效应不显著（P = 0.30）。
血清 sRAGE 水平与毛细支气管炎的急性和慢性疾病呈负相关。sRAGE 对反复喘息发展的影响可能是通过急性毛细支气管炎严重程度以外的途径产生的。
