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Biomedical subjects

Louise M O'Brien

Publications and source records attributed to Louise M O'Brien.

30 records · Page 2Linked to original sources

Sleep pressure correlates of cognitive and behavioral morbidity in snoring children.

STUDY OBJECTIVES: Sleep architecture is not preserved in children with sleep-disordered breathing but, rather, undergoes dynamic changes that exhibit significant correlation with severity of sleep-disordered breathing. A sleep pressure score (SPS) with a cutoff value of 0.25 was derived from analysis of a large cohort of snoring and control children. Neurocognitive batteries were applied to examine the potential effect of SPS. DESIGN: Prospective study. PARTICIPANTS: 199 children who underwent a battery of neurobehavioral tests following an overnight sleep study were assigned to SPSHigh (> or = 0.25) or SPSLow (< 0.25) groups, and their neurocognitive performances were compared. RESULTS: Children in the SPSHigh group were significantly more likely to have deficits in memory, language abilities, verbal abilities, and some visuospatial functions than were children in the SPSLow group. These effects remained highly significant after adjusting for confounding variables and exhibited small to moderate effect sizes. CONCLUSIONS: We conclude that a sleep-pressure numerical factor derived from the overnight polysomnogram in snoring children is associated with deficits in neurobehavioral daytime functions that is independent of respiratory disturbance and hypoxemia and suggests a significant role for disturbed sleep homeostasis in pediatric sleep-disordered breathing.

Child↗

Snoring and sleep-disordered breathing in young children: subjective and objective correlates.

STUDY OBJECTIVES: We sought to assess the predictive validity of parental report of snoring and other behaviors by comparing such reports with objective findings from overnight polysomnography for the evaluation of sleep-disordered breathing in 2 nonclinical samples, namely, at-risk preschoolers and an older group reflective of the general community. Predictive validity of snoring alone and a score based on multiple child behaviors were compared to outcome at different levels of severity of sleep-disordered breathing. DESIGN: Retrospective observational study. SETTING: Questionnaires were distributed through school programs; polysomnography was performed at Kosair Children's Hospital in Louisville, Kentucky. PARTICIPANTS: One hundred twenty-two preschoolers and 172 5- to 7-year-olds, and their parents, participated in both subjective-report and objective-recording portions of the study. MEASUREMENTS AND RESULTS: Compared to the presence of snoring on polysomnography, parental report of frequent snoring was highly sensitive and specific for both age groups. At all but the lowest level of severity of sleep-disordered breathing, predictive ability was higher for both groups when a parental-report score based on multiple measures of child behavior was applied, compared to parental report of snoring alone. The profiles of these predictive child behaviors differed between the 2 groups, as did their sensitivity and specificity, at their high ranges of parental report. CONCLUSIONS: Scores derived from parental-report questionnaires of children's snoring and other sleep and wake behaviors can be used as surrogate predictors of snoring or sleep-disordered breathing in children. However, design and interpretation should consider age, risk status, and the purpose of the screening assessment.

Child↗

Neurocognitive dysfunction and sleep in children: from human to rodent.

Sleep disturbance in children, whether because of poor sleep hygiene or sleep-related breathing disorders, is associated with significant behavioral and neurocognitive deficits. The mechanisms by which sleep disturbance contributes to the daytime manifestations are unclear, although it seems that sleep fragmentation and intermittent hypoxia are important. The long-term outcome for children with untreated diseases leading to sleep disruption is currently unknown. Increased awareness and early identification and treatment of conditions that lead to altered sleep should yield improved neurocognitive outcomes in affected children.

Animals↗

Snoring and obstructive sleep apnoea in children: why should we treat?

Frequent and loud snoring is a very frequent condition in prepubertal children affecting approximately 10% of all 2-8 year old children. If polysomnographical evaluations are performed in these snoring children, approximately 10% will be diagnosed with obstructive sleep apnoea (OSA). The pathophysiology of OSA in children is still poorly understood. Indeed, while adenotonsillar hypertrophy is certainly a major contributor to OSA, other factors need to be implicated for OSA to develop. In recent years, it has become apparent that OSA and snoring are not as innocuous as previously thought. Indeed, epidemiological and pre-post treatment analyses have identified substantial morbidities that primarily affect cardiovascular and neurobehavioural systems, namely pulmonary hypertension, systemic elevation of arterial blood pressure, nocturnal enuresis, reduced somatic growth, behavioural problems that resemble attention deficit-hyperactivity disorder, as well as learning and cognitive deficits. These problems are associated with marked increases in healthcare-related costs. More importantly, if timely diagnosis and intervention are not implemented, some of these morbid complications may not be completely reversible, leading to long-lasting residual consequences.

Behavior↗

Neurobehavioral correlates of sleep-disordered breathing in children.

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.

Aptitude↗

Plasma C-reactive protein levels among children with sleep-disordered breathing.

INTRODUCTION: Levels of C-reactive protein (CRP), an important serum marker of inflammation with major implications for cardiovascular morbidity and atherogenesis, are elevated among adult patients with sleep-disordered breathing (SDB). We hypothesized that elevated CRP plasma levels would also be present among children with SDB. METHODS: Eighty-one children (mean age: 9.3 +/- 3.7 years) underwent polysomnographic evaluations. Samples for plasma CRP level and lipid profile determinations were drawn the next morning. RESULTS: Because plasma CRP levels were not normally distributed in this cohort, logarithmic transformation was applied. Log plasma CRP levels were significantly higher in the SDB group (obstructive apnea/hypopnea index [AHI] of > or =5), compared with the mild SDB group (AHI of > or =1 and <5) and the control group (AHI of <1). Significant positive correlations were found between log CRP levels and AHI (r =.53) and arousal index (r =.28), whereas an inverse correlation was found between the lowest nocturnal arterial oxygen saturation and log CRP levels (r = -.47). These correlations persisted after exclusion of outliers. Moreover, 94% of the children with elevated log CRP levels reported excessive daytime sleepiness and/or learning problems, compared with 62% of the children with normal log CRP levels. CONCLUSIONS: Plasma CRP levels were increased among some children with SDB and were correlated with AHI, arterial oxygen saturation nadir, and arousal index measures. These changes were particularly prominent among children who were sleepy or presented with neurobehavioral complaints. The intermittent hypoxemia and sleep fragmentation of SDB may underlie inflammatory responses, the magnitude of which may ultimately lead to the cardiovascular, cognitive, and behavioral morbidities of SDB.

Analysis of Variance↗

Neurobehavioral implications of habitual snoring in children.

OBJECTIVE: Current guidelines for the treatment of children with obstructive sleep apnea (OSA) suggest that primary snoring (PS) in children is benign. However, PS has not been well evaluated, and it is unknown whether PS is associated with serious morbidity. This study investigated whether PS is associated with neurobehavioral deficits in children. METHODS: Parents of 5- to 7-year-old snoring children in public schools were surveyed about their child's sleeping habits. Children with a history of snoring and nonsnoring children were invited for overnight polysomnographic assessment and a battery of neurobehavioral tests. Only children who did not have a history of attention-deficit/hyperactivity disorder and were not considered hyperactive by parental report were tested. RESULTS: Children with a history of snoring, an obstructive apnea index of <1/hour of total sleep time (hrTST), an apnea/hypopnea index <5/hrTST, and no gas exchange abnormalities were classified as PS (n = 87). Control subjects were defined as children without a history of snoring, an obstructive apnea index <1/hrTST, an apnea/hypopnea index <5/hrTST, and no gas exchange abnormalities (n = 31). Although means for both groups were in the normal range, the PS children were found to perform worse on measures related to attention, social problems, and anxious/depressive symptoms. In addition, although within the normal range, both overall cognitive abilities and certain language and visuospatial functions were significantly lower for the PS group than for the control subjects. CONCLUSIONS: PS seems to be associated with significant neurobehavioral deficits in a subset of children, possibly related to increased susceptibility to sleep fragmentation. Larger studies are urgently required because current guidelines for treatment of snoring in children may require reevaluation.

Attention Deficit and Disruptive Behavior Disorder↗

The effect of stimulants on sleep characteristics in children with attention deficit/hyperactivity disorder.

OBJECTIVE: To investigate the effects of stimulant medications on subjective and objective sleep characteristics of children with attention deficit/hyperactivity disorder (ADHD) compared with control children. METHODS: An observational study in the sleep clinic and the community. Children with characteristics of ADHD, both stimulant-medicated (n=53), and non-medicated (n=34), together with control children (n=53) completed a sleep habits questionnaire prior to undergoing full overnight polysomnographic assessment. RESULTS: Medicated and non-medicated ADHD subjects were reported to have more sleep disturbances compared with controls. Both groups of ADHD children also demonstrated decreased REM sleep percentage compared with controls (P=0.006 for ADHDmed; P=0.02 for ADHDnon). However, the use of stimulant medication (n=53) was not associated with differences in subjective sleep quality or objective sleep measures, compared to ADHD children not taking any medication (n=34; P=n.s.). CONCLUSIONS: Despite the high prevalence of reported sleep disturbance in children with ADHD, stimulant medication appears to have minimal effects on subjective and objective sleep characteristics in children with reported ADHD.

Attention Deficit Disorder with Hyperactivity↗

Sleep and neurobehavioral characteristics of 5- to 7-year-old children with parentally reported symptoms of attention-deficit/hyperactivity disorder.

OBJECTIVES: This study examined the hypothesis that domains of neurobehavioral function would be selectively affected by sleep-disordered breathing (SDB). Therefore, we assessed potential relationships between objectively measured sleep disturbances and neurobehavioral function in children with reported symptoms of attention-deficit/hyperactivity disorder (ADHD) and also determined the incidence of snoring and other sleep problems in 5- to 7-year-old children in the local community and potential relationships to parental snoring and passive smoking. METHODS: Parents of 5- to 7-year-old children in public schools were surveyed about their child's sleeping habits using a validated questionnaire. The questionnaire also asked whether they believed their child to be hyperactive or have ADHD. Children with reported symptoms of ADHD and control children were randomly selected and invited to the Sleep Medicine Center for an overnight polysomnographic assessment and a battery of neurocognitive tests. RESULTS: The questionnaire response rate was 47.6% (n = 5728). Frequent and loud snoring was reported for 673 children (11.7%). Similarly, 418 (7.3%) children were reported to have hyperactivity/ADHD, 313 (76.5%) of which were boys. Eighty-three children with parentally reported symptoms of ADHD were invited for full evaluation at the Sleep Medicine Center together with 34 control children. After assessment with the Conners' Parent Rating Scale, 44 children were designated as having "significant" symptoms of ADHD, 27 as "mild," and 39 designated as "none" (controls). Overnight polysomnography indicated that obstructive sleep apnea was present in 5% of those with significant ADHD symptoms, 26% of those with mild symptoms, and 5% of those with no symptoms. In the cohort, no sleep variable accounted for more than a negligible proportion of the variance in domains of neurobehavioral function. CONCLUSIONS: An unusually high prevalence of snoring was identified among a group of children designated as showing mild symptoms of ADHD based on the Conners' ADHD index identified from a community sample. However, whereas SDB is not more likely to occur among children with significant ADHD symptoms, it is significantly highly prevalent among children with mild hyperactive behaviors. Sleep studies further revealed that rapid eye movement disturbances are more likely to occur in children with significant symptoms, and they seem to impose significant but mild effects on daytime neurobehavioral functioning. We conclude that in children with significant symptoms of ADHD, the prevalence of SDB is not different from that of the general pediatric population and that rapid eye movement sleep in these children is disturbed and may contribute to the severity of their behavioral manifestations. Furthermore, SDB can lead to mild ADHD-like behaviors that can be readily misperceived and potentially delay the diagnosis and appropriate treatment.

Age Factors↗

Staphylococcus aureus clumping factor B (ClfB) promotes adherence to human type I cytokeratin 10: implications for nasal colonization.

Staphylococcus aureus is an important cause of sepsis in both community and hospital settings, a major risk factor for which is nasal carriage of the bacterium. Eradication of carriage by topical antibiotics reduces sepsis rates in high-risk individuals, an important strategy for the reduction of nosocomial infection in targeted patient populations. Understanding the mechanisms by which S. aureus adheres to nasal epithelial cells in vivo may lead to alternative methods of decolonization that do not rely on sustained antimicrobial susceptibility. Here, we demonstrate for the first time that the S. aureus surface-expressed protein, clumping factor B (ClfB), promotes adherence to immobilized epidermal cytokeratins in vitro. By expressing a range of S. aureus adhesins on the surface of the heterologous host Lactococcus lactis, we demonstrated that adherence to epidermal cytokeratins was conferred by ClfB. Adherence of wild-type S. aureus was inhibited by recombinant ClfB protein or anti-ClfB antibodies, and S. aureus mutants defective in ClfB adhered poorly to epidermal cytokeratins. Expression of ClfB promoted adherence of L. lactis to human desquamated nasal epithelial cells, and a mutant of S. aureus defective in ClfB had reduced adherence compared with wild type. ClfB also promoted adherence of L. lactis cells to a human keratinocyte cell line. Cytokeratin 10 molecules were shown by flow cytometry to be exposed on the surface of both desquamated nasal epithelial cells and keratinocytes. Cytokeratin 10 was also detected on the surface of desquamated human nasal cells using immunofluorescence, and recombinant ClfB protein was shown to bind to cytokeratin K10 extracted from these cells. We also showed that ClfB is transcribed by S. aureus in the human nares. We propose that ClfB is a major determinant in S. aureus nasal colonization.

Adhesins, Bacterial↗

Behavioural and neurocognitive implications of snoring and obstructive sleep apnoea in children: facts and theory.

The pathophysiology of obstructive sleep apnoea (OSA), a common condition in children, is poorly understood. While adenotonsillar hypertrophy is certainly a major contributor, other factors are needed for OSA to develop. OSA has been associated with substantial morbidities primarily affecting cardiovascular and neurobehavioural systems which may not be completely reversed with appropriate treatment. This paper reviews the available information and attempts to provide the rationale for early diagnosis and treatment of OSA in children.

Child↗