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Contextualised urinary biomarker analysis facilitates diagnosis of paediatric obstructive sleep apnoea.

ABSTRACT: Intrinsic variance of the urine proteome limits the discriminative power of proteomic analysis and complicates potential biomarker detection in the context of paediatric sleep disorders.Using a rigorous workflow for proteomic analysis of urine, we demonstrate that gender and diurnal effects constitute two important sources of variability in healthy children. In the context of disease, complex pathophysiological perturbations magnify these proteomic differences and therefore require contextualised biomarker analysis. Indeed, by performing biomarker discovery in a gender- and diurnal-dependent manner, we identified ?30-fold more candidate biomarkers of paediatric obstructive sleep apnoea (OSA), a highly prevalent condition in children characterised by repetitive episodes of intermittent hypoxia and hypercapnia, and sleep fragmentation in the context of recurrent upper airway obstructive events during sleep. Remarkably, biomarkers were highly specific for gender and sampling time as poor overlap (?3%) was observed in the proteins identified in boys and girls across morning and bedtime samples.As no clinical basis to explain gender-specific effects in OSA or healthy children is apparent, we propose that implementation of contextualised biomarker strategies will be applicable to a broad range of human diseases, and may be specifically applicable to paediatric OSA.

SUBMITTER: Becker L

PROVIDER: S-EPMC4247538 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Contextualised urinary biomarker analysis facilitates diagnosis of paediatric obstructive sleep apnoea.

Becker Lev L Kheirandish-Gozal Leila L Peris Eduard E Schoenfelt Kelly Q KQ Gozal David D

Sleep medicine 20140207 5

<h4>Background</h4>Intrinsic variance of the urine proteome limits the discriminative power of proteomic analysis and complicates potential biomarker detection in the context of paediatric sleep disorders.<h4>Methods and results</h4>Using a rigorous workflow for proteomic analysis of urine, we demonstrate that gender and diurnal effects constitute two important sources of variability in healthy children. In the context of disease, complex pathophysiological perturbations magnify these proteomic ...[more]

PMID: 24726570

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Project description:The roles of central nervous mechanisms and cortical output in obstructive sleep apnoea remain unclear. We addressed corticomuscular coupling between cortical sensorimotor areas and lower facial motor units as a mechanistic pathway and as a possible surrogate marker of corticoperipheral motor control in obstructive sleep apnoea. In this exploratory cross-sectional retrospective study, we analysed EEG (C3 and C4 leads) and chin EMG from polysomnography recordings in 86 participants (22 females; age range: 26-81?years): 27 with mild (respiratory disturbance index = 5-15 events/h), 21 with moderate (15-30 events/h) and 23 with severe obstructive sleep apnoea (>30 events/h) and 15 control subjects (<5 events/h). By computing C3-/C4-EEG-chin EMG coherence of signal dynamics in time and frequency domains, we investigated corticomuscular coupling between cortical sensorimotor areas and lower facial motor units with increasing obstructive sleep apnoea severity during the entire sleeping time, during different sleep stages and during obstructive respiratory events, including 5?s before (stable breathing) and after events (breathing resumption). In addition, we studied a possible influence of body mass index and autonomic nervous system activation. We found that both average and respiratory event-specific corticomuscular coupling between cortical sensorimotor areas and lower facial motor units weakened significantly with increasing obstructive sleep apnoea severity, was strongest during N3 and weakened in N1, N2 and rapid eye movement stages (in decreasing order). Coupling increases significantly during the obstructive respiratory events compared with coupling just before and following them. Results were independent of body mass index or autonomic nervous system activation. We conclude that obstructive respiratory events in obstructive sleep apnoea are very strongly associated both quantitatively and temporally with the degree of disconnection within the cortical sensorimotor areas-lower facial motor units pathway. This quite coordinated activity pattern suggests a cortical sensorimotor area-driven obstructive respiratory event pattern generator and a central motor output disorder in obstructive sleep apnoea.

Dataset Information

Contextualised urinary biomarker analysis facilitates diagnosis of paediatric obstructive sleep apnoea.

Publications

Contextualised urinary biomarker analysis facilitates diagnosis of paediatric obstructive sleep apnoea.

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