Department of Pediatrics, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
NeuroScience, Inc, Osceola, WI.
Chest. 2013 Jun;143(6):1576-1583. doi: 10.1378/chest.12-2606.
Pediatric obstructive sleep apnea (OSA) is associated with cognitive dysfunction, suggesting altered neurotransmitter function. We explored overnight changes in neurotransmitters in the urine of children with and without OSA.
Urine samples were collected from children with OSA and from control subjects before and after sleep studies. A neurocognitive battery assessing general cognitive ability (GCA) was administered to a subset of children with OSA. Samples were subjected to multiple enzyme-linked immunosorbent assays for 12 neurotransmitters, and adjusted for creatinine concentrations.
The study comprised 50 children with OSA and 20 control subjects. Of the children with OSA, 20 had normal GCA score (mean ± SD) (101.2 ± 14.5) and 16 had a reduced GCA score (87.3 ± 13.9; P < .001). Overnight increases in epinephrine, norepinephrine, and γ-aminobutyric acid (GABA) levels emerged in children with OSA; taurine levels decreased. Using combinatorial approaches and cutoff values for overnight changes of these four neurotransmitters enabled prediction of OSA (area under the curve [AUC]: 0.923; P < .0001). Furthermore, GABA and taurine alterations, as well as overnight reductions in phenylethylamine, were more prominent in children with OSA and low GCA than in children with OSA and normal GCA (P < .001), and they reliably discriminated GCA status (AUC: 0.977; P < .0001).
Pediatric OSA is associated with overnight increases in urinary concentrations of catecholamines indicative of heightened sympathetic outflow. Increases in GABA levels and decreases in taurine levels could underlie mechanisms of neuronal excitotoxicity and dysfunction. Combinatorial approaches using defined cutoffs in overnight changes in concentrations of selected neurotransmitters in urine may not only predict OSA but also the presence of cognitive deficits. Larger cohort studies appear warranted to confirm these findings.
小儿阻塞性睡眠呼吸暂停（OSA）与认知功能障碍有关，表明神经递质功能发生改变。我们探讨了伴有和不伴有 OSA 的儿童尿液中神经递质的夜间变化。
在睡眠研究前后，从 OSA 患儿和对照组患儿中采集尿液样本。对 OSA 患儿的亚组进行了评估一般认知能力（GCA）的神经认知测试。对尿液样本进行了 12 种神经递质的多酶联免疫吸附测定，并按肌酐浓度进行了调整。
该研究包括 50 例 OSA 患儿和 20 例对照组患儿。在 OSA 患儿中，20 例 GCA 评分正常（平均值±标准差）（101.2±14.5），16 例 GCA 评分降低（87.3±13.9；P <.001）。OSA 患儿夜间肾上腺素、去甲肾上腺素和γ-氨基丁酸（GABA）水平升高；牛磺酸水平下降。使用组合方法和这些四种神经递质的夜间变化的截断值可以预测 OSA（曲线下面积 [AUC]：0.923；P <.0001）。此外，与 OSA 患儿和正常 GCA 相比，OSA 患儿和低 GCA 患儿中 GABA 和牛磺酸的改变以及苯乙胺的夜间减少更为明显（P <.001），并且它们可靠地区分了 GCA 状态（AUC：0.977；P <.0001）。
小儿 OSA 与夜间儿茶酚胺浓度升高有关，提示交感神经输出增加。GABA 水平升高和牛磺酸水平降低可能是神经元兴奋性毒性和功能障碍的机制。使用尿液中选定神经递质的浓度在夜间变化的定义截值进行组合方法不仅可以预测 OSA，还可以预测认知缺陷的存在。需要更大的队列研究来证实这些发现。
