脓毒症所致儿童急性低氧性呼吸衰竭的内型证据。
Evidence of Endotypes in Pediatric Acute Hypoxemic Respiratory Failure Caused by Sepsis.
机构信息
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA.
Division of Pediatric Critical Care Medicine, Department of Pediatrics and Public Health Science, Penn State Hershey Children's Hospital, Hershey, PA.
出版信息
Pediatr Crit Care Med. 2019 Feb;20(2):110-112. doi: 10.1097/PCC.0000000000001808.
OBJECTIVES
Subclassification based on clinical or biologic commonalities (endotypes) is one approach to reduce heterogeneity in acute hypoxemic respiratory failure. In adults, biomarker-defined endotypes of respiratory failure have been described, with differential outcome profiles and response to therapy. To date, no studies have tested whether endotypes exist in pediatric acute hypoxemic respiratory failure, although messenger RNA expression-based endotypes have been described in pediatric sepsis. The aim of the present study was to test whether endotypes identified in pediatric sepsis are applicable to pediatric acute hypoxemic respiratory failure.
DESIGN
Secondary analysis of a previously reported microarray-based study of pediatric sepsis.
SETTING
Multiple PICUs in the United States.
PATIENTS
Sixty-seven children with acute hypoxemic respiratory failure caused by sepsis.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Of the larger septic shock cohort, 67 met eligibility for acute hypoxemic respiratory failure. Twenty-three subjects were assigned to endotype A, and 44 to endotype B. Subjects assigned to endotype A had over four-fold greater unadjusted 28-day mortality, and nearly three-fold greater rates of complicated course. The association with mortality (odds ratio, 8.0; 95% CI, 1.6-41.0) and complicated course (odds ratio, 4.2; 95% CI, 1.2-14.9) persisted after adjustment for age, severity of illness, and PaO2/FIO2.
CONCLUSIONS
Applying a previously reported endotyping strategy in children with septic shock identified endotypes of pediatric acute hypoxemic respiratory failure secondary to sepsis, with differential risk for poor outcomes. To our knowledge, this is the first demonstration of endotypes in pediatric respiratory failure. Our results support an investigation into using transcriptomics to identify messenger RNA-based endotypes in a dedicated, well-defined acute hypoxemic respiratory failure cohort.
目的
基于临床或生物学共性（表型）的亚分类是减少急性低氧性呼吸衰竭异质性的一种方法。在成人中，已经描述了基于生物标志物的呼吸衰竭表型，具有不同的预后特征和对治疗的反应。迄今为止，尚无研究测试儿科急性低氧性呼吸衰竭是否存在表型，尽管已经在儿科脓毒症中描述了基于信使 RNA 表达的表型。本研究旨在测试在儿科脓毒症中确定的表型是否适用于儿科急性低氧性呼吸衰竭。
设计
先前报告的基于小儿脓毒症微阵列研究的二次分析。
地点
美国多个 PICUs。
患者
67 例由脓毒症引起的急性低氧性呼吸衰竭儿童。
干预措施
无。
测量和主要结果
在较大的脓毒性休克队列中，有 67 名符合急性低氧性呼吸衰竭的入选标准。23 名受试者被分配到表型 A，44 名受试者被分配到表型 B。被分配到表型 A 的受试者未经调整的 28 天死亡率高出四倍多，且并发症发生率几乎高出三倍。死亡率（比值比，8.0；95%置信区间，1.6-41.0）和复杂病程（比值比，4.2；95%置信区间，1.2-14.9）的相关性在调整年龄、疾病严重程度和 PaO2/FIO2 后仍然存在。
结论
在脓毒性休克患儿中应用先前报道的表型策略确定了继发于脓毒症的儿科急性低氧性呼吸衰竭的表型，预后不良的风险不同。据我们所知，这是首次在儿科呼吸衰竭中证明表型的存在。我们的结果支持使用转录组学在专门定义明确的急性低氧性呼吸衰竭队列中识别基于信使 RNA 的表型的研究。
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