Peripheral Blood Leukocyte Gene Expression Patterns and Metabolic Parameters in Habitually Snoring and Non-Snoring Children with Normal Polysomnographic Findings

Gharib, Sina A.; Kim, Jinkwan; Capdevila, Óscar Sans; Kheirandish‐Gozal, Leila; Bhattacharjee, Rakesh; Hegazi, Mohamed M.; Gozal, David

doi:10.1093/sleep/34.2.153

Cited by 29 publications

(25 citation statements)

References 59 publications

(60 reference statements)

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“…These differences were variable but clearly present and require a more detailed examination, given the recognition that children of color often grow up in less advantaged socioeconomic circumstances with coexisting differences in educational opportunities. Similarly, although children in this sample differed across communities in terms of educational opportunity and engagement (43), because this study includes samples from two diverse communities in different sections of the United States who were assessed with a similar approach with consistent comparisons made using relevant normative data that includes similar samples, we believe that the findings are strongly representative of children living in a mixed urban setting. Nonetheless, there may be underlying variabilities that we have not successfully accounted for Error bars represent SE.…”

Section: Discussionmentioning

confidence: 99%

Effect of Sleep-disordered Breathing Severity on Cognitive Performance Measures in a Large Community Cohort of Young School-aged Children

Hunter

Gozal

Smith

et al. 2016

Am J Respir Crit Care Med

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212

173

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Rationale: Sleep-disordered breathing (SDB) in children is associated with cognitive challenges. However, potential associations between SDB severity and neurocognitive function, as well as the presence of an SDB cutoff, have not been fully explored.Objectives: To determine whether SDB-associated adverse changes in neurocognitive functioning are severity dependent.Methods: A total of 1,010 snoring and nonsnoring children ages 5-7 years were prospectively recruited from public schools and underwent polysomnography and neurocognitive assessments of intellectual, attention, memory, language, and executive function development. The children were subdivided into four severity groups on the basis of apnea-hypopnea index (AHI), followed by comparisons of cognitive function, with a particular focus on standardized subtests of intellectual, language, attention, memory, and executive function.Measurement and Main Results: Differential Ability Scales Verbal (P , 0.001) and Nonverbal (P = 0.002) performance, as well as global conceptual ability (IQ) (P , 0.001) scores, differed significantly across the groups, with individuals with higher AHI showing worse performance. Additionally, specific NEPSY (a Developmental Neuropsychological Assessment) subscores focused on attention and executive skills differed across the groups, indicating differences in levels of engagement and problem solving. Children with higher AHI (.5 per hour of total sleep time) were significantly more impaired than all three lower AHI groups, indicating a dose-response impact of SDB.Conclusions: This large community-based sample of children highlights the significant deleterious impact of SDB, particularly in children with moderate to severe obstructive sleep apnea, and also that even snoring alone affects neurocognitive function. By affecting developing capabilities, as illustrated by cognitive measures in a severity-graded manner, SDB could adversely impact children's capacity to attain academic and adaptive goals, ultimately hampering their ability to reach independence. Our findings support the need for increased awareness of SDB, with particular emphasis on children with more severe obstructive sleep apnea.

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Section: Discussionmentioning

confidence: 99%

Effect of Sleep-disordered Breathing Severity on Cognitive Performance Measures in a Large Community Cohort of Young School-aged Children

Hunter

Gozal

Smith

et al. 2016

Am J Respir Crit Care Med

Self Cite

212

173

View full text Add to dashboard Cite

show abstract

“…In other words, the optimal threshold for diagnosis and treatment is likely different in different children. Simply stated, not every child fulfilling current polysomnographic criteria for OSA manifests end-organ morbidity,173 and conversely, some children with primary snoring display neurocognitive or cardiovascular sequelae and/or signs of systemic inflammation, despite a normal sleep study 90,110…”

Section: Future Developmentsmentioning

confidence: 99%

Obstructive sleep apnea in children: a critical update

Tan¹,

Gozal²,

Kheirandish‐Gozal³

2013

NSS

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105

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Obstructive sleep apnea (OSA) in children is a highly prevalent disorder caused by a conglomeration of complex pathophysiological processes, leading to recurrent upper airway dysfunction during sleep. The clinical relevance of OSA resides in its association with significant morbidities that affect the cardiovascular, neurocognitive, and metabolic systems. The American Academy of Pediatrics recently reiterated its recommendations that children with symptoms and signs suggestive of OSA should be investigated with polysomnography (PSG), and treated accordingly. However, treatment decisions should not only be guided by PSG results, but should also integrate the magnitude of symptoms and the presence or absence of risk factors and signs of OSA morbidity. The first-line therapy in children with adenotonsillar hypertrophy is adenotonsillectomy, although there is increasing evidence that medical therapy, in the form of intranasal steroids or montelukast, may be considered in mild OSA. In this review, we delineate the major concepts regarding the pathophysiology of OSA, its morbidity, diagnosis, and treatment.

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“…The altered expression of functionally relevant gene clusters was confirmed and a significant number of these genes mapped to inflammatory processes, providing further support to OSA being a systemic inflammatory disorder. Interestingly, subtle changes in the transcriptome of peripheral blood leukocytes could already be detected in children with primary snoring, compared with matched non-snoring controls, and in these children, altered signalling modules mapping to glucose homeostasis and insulin signalling were detected and confirmed 35. We would surmise that these approaches in exquisitely carefully phenotyped patients may enable identification of candidate pathways underlying unique susceptibility, and offer opportunities for precise categorical risk assessments.…”

Section: Genomic and Proteomic Approaches To Diagnosismentioning

confidence: 91%

The promise of translational and personalised approaches for paediatric obstructive sleep apnoea: an ‘Omics’ perspective

Tan

Kheirandish‐Gozal

Gozal

2014

Thorax

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Obstructive sleep apnoea (OSA) can result in significant morbidities including the cardiovascular, metabolic and neurocognitive systems. These effects are purportedly mediated via activation of inflammatory cascades and the induction of oxidative stress, ultimately resulting in cellular injury and dysfunction. While great advances have been made in sleep medicine research in the past decades, there are still wide gaps in our knowledge concerning the exact underlying pathophysiological mechanisms of OSA and consequences. Without resolving these issues, the reasons why patients with a similar severity of OSA can have markedly different clinical presentation and end-organ morbidity, that is, phenotype, will continue to remain elusive. This review aims to highlight the recent exciting discoveries in genotype-phenotype interactions, epigenetics, genomics and proteomics related to OSA. Just as PCR revolutionised the field of genetics, the potential power of 'Omics' promises to transform the field of sleep medicine, and provide critical insights into the downstream pathological cascades inherent to OSA, thereby enabling personalised diagnosis and management for this highly prevalent sleep disorder.

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Peripheral Blood Leukocyte Gene Expression Patterns and Metabolic Parameters in Habitually Snoring and Non-Snoring Children with Normal Polysomnographic Findings

Cited by 29 publications

References 59 publications

Effect of Sleep-disordered Breathing Severity on Cognitive Performance Measures in a Large Community Cohort of Young School-aged Children

Effect of Sleep-disordered Breathing Severity on Cognitive Performance Measures in a Large Community Cohort of Young School-aged Children

Obstructive sleep apnea in children: a critical update

The promise of translational and personalised approaches for paediatric obstructive sleep apnoea: an ‘Omics’ perspective

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