Researcher Develops Urine Test for identifying Sleep Apnea in Children. Will this change lead to early diagnosis and prevention of ADD and ADHD

WFPL news reported

"University of Louisville researcher Dr. Saeed Jortani has developed a urine test that could soon be used to screen or diagnose children with obstructive sleep apnea. He says children have been difficult to diagnose because of the required overnight stay in a sleep clinic.
Jortani says they looked for another way to screen children, so fewer would have to get tested, and found the answer in urine.
“Whatever the body does throughout the day, urine is basically a record of what’s going on for the previous several hours,” says Jortani, “and we thought if the child is under stress or if the child is having difficulty breathing, that has to affect some of the proteins in their body.”
Jortani says children who suffer from the sleep disorder have a high level of stress-related protein in their urine. He says in the future, children who test positive in the urine test will then go on to tests in a sleep clinic.
He says in future research, he may develop the test for adults"

Screening for sleep apnea was also the subject of a recent repot from the University of Chicago (see PubMed abstract below). They concluded in Am J Respir Crit Care Med. 2009 Dec 15;180(12):1253-61 "CONCLUSIONS: Proteomic approaches reveal that pediatric OSA is associated with specific and consistent alterations in urinary concentrations of specific protein clusters. Future studies aiming to validate this approach as a screening method of habitually snoring children appears warranted."
Their study showed extremely high sensitivity and specificity.

Another study in Chest. 2009 Jun;135(6):1496-501 (see PUBMED abstract below) showed that "Urine concentrations of cysteinyl leukotrienes in children with obstructive sleep-disordered breathing" could be used to predict severity of pediatric sleep apnea. It is well known that neurocognitive effects of sleep apnea include increases in ADD, ADHD, Dyslexia and other behavioral disorders as recently reported in Pediatr Pulmonol. 2009 May;44(5):417-22 in an article titled "Neurocognitive and behavioral impact of sleep disordered breathing in children."

The question is do these metabolic changes measured in the urine act just as a marker to identify sleep apnea or can the chemical changes measured actually be causing the toxic effects on brain development and maturation?

The development of the craniomandibular articulation and the size of the palate and oral cavity are easily correctable at early ages to eliminate snoring and sleep apnea. The NHLBI considers Sleep Apnea to be a TMJ disorder. Correction of aberrant oral devlopment can probably prevent sleep apnea, and tmj problems and headaches in adults. Babies who are breastfed are less likely to develop these problems to begin with. Dentistry and early orthodontic airway orthopedics may be ables to drastically reduce future medical and educational costs by preventing sleep apnea and/or diagnosing and treating at an early stage prior to adverse neurocognitive changes.

PubMed abstracts below:
Am J Respir Crit Care Med. 2009 Dec 15;180(12):1253-61. Epub 2009 Sep 24.
Two-dimensional differential in-gel electrophoresis proteomic approaches reveal urine candidate biomarkers in pediatric obstructive sleep apnea.
Gozal D, Jortani S, Snow AB, Kheirandish-Gozal L, Bhattacharjee R, Kim J, Capdevila OS.

Section of Pediatric Sleep Medicine, Department of Pediatrics, University of Chicago, Chicago, Illinois, USA. dgozal@peds.bsd.uchicago.edu
RATIONALE: Sleep studies are laborious, expensive, inaccessible, and inconvenient for diagnosing obstructive sleep apnea (OSA) in children. OBJECTIVES: To examine whether the urinary proteome uncovers specific clusters that are differentially expressed in the urine of children with OSA. METHODS: Two-dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry proteomics followed by validation with western blot of ELISA. MEASUREMENTS AND MAIN RESULTS: Morning urine proteins from 60 children with polysomnographically confirmed OSA and from matched children with primary snoring (n = 30) and control subjects (n = 30) were assessed. A total of 16 proteins that are differentially expressed in OSA were identified, and 7 were confirmed by either immunoblots or ELISA. Among the latter, receiver-operator curve analyses of urinary concentrations of uromodulin, urocortin-3, orosomucoid-1, and kallikrein assigned favorable predictive properties to these proteins. Furthermore, combinatorial approaches indicated that the presence of values beyond the calculated cutoff concentrations for three or more of the proteins yielded a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: Proteomic approaches reveal that pediatric OSA is associated with specific and consistent alterations in urinary concentrations of specific protein clusters. Future studies aiming to validate this approach as a screening method of habitually snoring children appears warranted.

PMID: 19797158 [PubMed - indexed for MEDLINE]

Chest. 2009 Jun;135(6):1496-501. Epub 2009 Jan 13.
Urine concentrations of cysteinyl leukotrienes in children with obstructive sleep-disordered breathing.
Kaditis AG, Alexopoulos E, Chaidas K, Ntamagka G, Karathanasi A, Tsilioni I, Kiropoulos TS, Zintzaras E, Gourgoulianis K.

Sleep Disorders Laboratory, University of Thessaly School of Medicine and Larissa University Hospital, Larissa, Greece. Kaditia@hotmail.com
BACKGROUND: Adenotonsillar tissue of children with obstructive sleep-disordered breathing (SDB) has increased content of cysteinyl leukotrienes (CysLTs) and expression of CysLTs receptors. Furthermore, CysLTs concentrations in the nasal exhaled breath condensate of children with sleep apnea are elevated. OBJECTIVE: To investigate the relationship between urine levels of CysLTs and severity of SDB in children. METHODS: Morning urine concentrations of CysLTs were measured in children with symptoms of SDB and in control subjects with recurrent tonsillitis and without snoring who underwent polysomnography and were expressed in pg/mL per mg/dL of urine creatinine. RESULTS: Nineteen children with moderate-to-severe SDB (mean [+/- SD] age, 5.4 +/- 1.6 years; obstructive apnea-hypopnea index [OAHI]: 14.4 +/- 9.6 episodes/h), 29 subjects with mild SDB (5.1 +/- 1.5 years; OAHI: 2.9 +/- 0.8 episodes/h), 26 children with primary snoring (PS) [7 +/- 2.6 years; OAHI: 1.1 +/- 0.3 episodes/h], and 18 control subjects (6.4 +/- 2.5 years; OAHI: 0.7 +/- 0.3 episodes/h) were studied. Children with moderate-to severe SDB had higher log-transformed urine CysLTs levels than those with mild SDB, PS, or control subjects (2.39 +/- 0.51 vs 2.06 +/- 0.26 vs 2.11 +/- 0.25 vs 1.86 +/- 0.28; p < 0.05). Log-transformed CysLTs concentration, tonsillar size, and body mass index z score were significant predictors of log-transformed OAHI (p < 0.01). CONCLUSIONS: Urine excretion of CysLTs is related to SDB severity in children. This finding indicates that 5-lipoxygenase pathway products participate in the pathogenesis of obstructive sleep apnea in childhood or alternatively that SDB promotes CysLTs biosynthesis.

PMID: 19141528 [PubMed - indexed for MEDLINE]

Pediatr Pulmonol. 2009 May;44(5):417-22.
Neurocognitive and behavioral impact of sleep disordered breathing in children.
Owens JA.

Department of Ambulatory Pediatrics, Rhode Island Hospital, Providence, Rhode Island 02903, USA. owensleep@gmail.com
The consequences of poor quality and/or inadequate sleep in children and adolescents have become a major public health concern, and one in which pediatric health care professionals have become increasingly involved. In particular, insufficient and/or fragmented sleep resulting from primary sleep disorders such as obstructive sleep apnea (OSA), often compounded by the presence of comorbid sleep disorders as well as by voluntary sleep curtailment related to lifestyle and environmental factors, has been implicated in a host of negative consequences. These range from metabolic dysfunction and increased cardiovascular morbidity to impairments in mood and academic performance. The following review will focus on what is currently known about the effects of sleep disordered breathing (SDB) specifically on neurobehavioral and neurocognitive function in children. Because of the scarcity of literature on the cognitive and behavioral impact of sleep disorders in infants and very young children, this review will target largely the preschool/school-aged child and adolescent populations. In addition, the focus will be on a review of the most recent literature, as a supplement to several excellent previous reviews on the topic. (c) 2009 Wiley-Liss, Inc.

PMID: 19382210 [PubMed - indexed for MEDLINE]