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Original Research: Sleep Disorders |

Urinary Neurotransmitters Are Selectively Altered in Children With Obstructive Sleep Apnea and Predict Cognitive MorbidityUrine Biomarkers in Pediatric Sleep Apnea

Leila Kheirandish-Gozal, MD; Corena J. T. McManus, MS; Gottfried H. Kellermann, PhD; Arash Samiei, MD; David Gozal, MD, FCCP
Author and Funding Information

From the Department of Pediatrics (Drs Kheirandish-Gozal, Samiei, and Gozal), Pritzker School of Medicine, The University of Chicago, Chicago, IL; and NeuroScience, Inc (Ms McManus and Dr Kellermann), Osceola, WI.

Correspondence to: David Gozal, MD, FCCP, Department of Pediatrics, Comer Children’s Hospital, The University of Chicago, 5721 S Maryland Ave, MC 8000, Ste K-160 Chicago, IL 60637; e-mail: dgozal@uchicago.edu


Funding/Support: This study was supported in part by US National Institutes of Health [grants HL-65270 and HL107160 to Dr Gozal].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(6):1576-1583. doi:10.1378/chest.12-2606
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Background:  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.

Methods:  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.

Results:  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).

Conclusions:  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.

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