Elsharkawi Ibrahim, Gozal David, Macklin Eric A, Voelz Lauren, Weintraub Gil, Skotko Brian G
Down Syndrome Program, Division of Genetics, Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA.
Department of Pediatrics, University of Chicago, Chicago, IL, USA.
Sleep Med. 2017 Jun;34:84-89. doi: 10.1016/j.sleep.2017.02.005. Epub 2017 Mar 7.
The study aimed to compare urinary biomarkers in patients with Down syndrome (DS) with and without obstructive sleep apnea (OSA) to those of age- and sex-matched neurotypically developing healthy controls (HC). We further investigated whether we could predict OSA in patients with DS using these biomarkers.
Urine samples were collected from 58 patients with DS the night before or the morning after their scheduled overnight polysomnogram or both, of whom 47 could be age- and sex-matched to a sample of 43 HC. Concentrations of 12 neurotransmitters were determined by enzyme-linked immunosorbent assay. Log-transformed creatinine-corrected assay levels were normalized. Normalized z-scores were compared between patients with DS vs. HC, between patients with DS with vs. without OSA, and to derive composite models to predict OSA.
Most night-sampled urinary biomarkers were elevated among patients with DS relative to matched HC. No urinary biomarker levels differed between patients with DS with vs. without OSA. A combination of four urinary biomarkers predicted AHI > 1 with a positive predictive value of 90% and a negative predictive value of 68%.
Having DS, even in the absence of concurrent OSA, is associated with a different urinary biomarker profile when compared to that of HC. Therefore, while urinary biomarkers may be predictive of OSA in the general pediatric population, a different approach is needed in interpreting urinary biomarker assays in patients with DS. Certain biomarkers also seem promising to be predictive of OSA in patients with DS. No clinical trial was indicated in the undertaking of this work.
本研究旨在比较患有和未患有阻塞性睡眠呼吸暂停（OSA）的唐氏综合征（DS）患者与年龄和性别匹配的神经发育正常的健康对照者（HC）的尿液生物标志物。我们进一步研究了是否可以使用这些生物标志物预测DS患者的OSA。
在58例DS患者进行预定的夜间多导睡眠图检查的前一晚或后一天早晨或两者均采集尿液样本，其中47例患者在年龄和性别上可与43例HC的样本匹配。通过酶联免疫吸附测定法测定12种神经递质的浓度。对经肌酐校正的测定水平进行对数转换并标准化。比较DS患者与HC之间、患有和未患有OSA的DS患者之间的标准化z分数，并推导预测OSA的综合模型。
相对于匹配的HC，DS患者中大多数夜间采样的尿液生物标志物升高。患有和未患有OSA的DS患者之间的尿液生物标志物水平没有差异。四种尿液生物标志物的组合预测呼吸暂停低通气指数（AHI）>1，阳性预测值为90%，阴性预测值为68%。
与HC相比，患有DS，即使没有并发OSA，也与不同的尿液生物标志物谱相关。因此，虽然尿液生物标志物可能在一般儿科人群中预测OSA，但在解释DS患者的尿液生物标志物检测结果时需要采用不同的方法。某些生物标志物似乎也有望预测DS患者的OSA。本研究未开展临床试验。
