New biomarker identified for the diagnosis of obstructive sleep apnoea in children

CHICAGO – Diagnosing obstructive sleep apnoea (OSA) in children may soon become as easy as a walk in the park. A new study suggests that a urine test can differentiate sleep apnoea from uncomplicated snoring.

Findings published in the American Journal of Respiratory Critical Care show that, in children, OSA is associated with reproducible alterations in the urinary proteome, and that such changes can potentially be used to screen children who snore.

OSA is relatively frequent in children: about 3% exhibit the signs and symptoms of OSA before puberty. Recently, OSA has been associated with neurocognitive and cardiovascular morbidities. Children who snore, but who do not have gas exchange abnormalities or evidence of snore-associated alterations in sleep architecture, are considered to have primary snoring (PS), an extremely frequent condition affecting 10–12% of all school-aged children.

The difficulty lies in differentiating the two conditions.

According to researchers from the University of Chicago, “Sleep studies are laborious, expensive, inaccessible, and inconvenient for diagnosing [OSA] in children.”

They therefore started looking at other means of diagnosing the sleep disorder reliably in children.
Professor of Paediatrics David Gozal and his colleagues studied 120 children (90 of whom had been referred to a sleep clinic to be evaluated for suspected sleep disordered breathing) and 30 healthy, non-snoring children to serve as controls.

The children all underwent standard overnight polysomnography and were categorised as having either OSA, habitual snoring or no sleep disordered breathing. A sample of urine was collected the morning after the sleep study.

Using 2-dimensional differential in-gel electrophoresis and other techniques, the researchers screened hundreds of candidate proteins in the urine. They found that some of the urinary proteins were present at different concentrations in children with sleep apnoea.

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 tested proteins, elevated urinary concentrations of uromodulin, urocortin-3, orosomucoid-1, and kallikrein indicated the presence of sleep apnoea. The presence of values beyond the calculated cut-off concentrations for three or more of these proteins yielded a sensitivity of 95% and a specificity of 100%.

“The morning urine samples from 60 children fulfilling the polysomnographic and clinical criteria of OSA revealed selective and consistent alterations in specific components of the urinary proteome,” summarises Dr Gozal.

“However,” he concludes, “the potential effects of coexisting diseases or of acute infections on these urinary marker patterns will need to be ascertained.”

Reference:

Gozal D. et al. Am J Respir Crit Care Med. 2009 Dec 15;180(12):1253-61

Photo credit: Ganfyd