Showing papers by "Carole L. Marcus published in 2011"

The Childhood Adenotonsillectomy Trial (CHAT): Rationale, Design, and Challenges of a Randomized Controlled Trial Evaluating a Standard Surgical Procedure in a Pediatric Population

Abstract: Each year, over 500,000 adenotonsillectomies (AT), mostly for the treatment of pediatric obstructive sleep apnea (OSA) are performed in the US in children under 15 years of age. No definitive study, however, has been yet conducted that has rigorously evaluated the effectiveness of AT for not only improving sleep disordered breathing, but also for improving clinically relevant outcomes, such as neurocognitive function, behavior, and quality of life. The Childhood Adenotonsillectomy Trial (CHAT) was designed to assess neuropsychological and health outcomes in children randomized to receive early AT (eAT) as compared to Watchful Waiting with Supportive Care (WWSC). Important secondary goals of the study are to evaluate outcomes in subgroups defined by obesity and race. This paper addresses key elements in the design and implementation of a controlled trial for a widely used "standard practice" surgical intervention in a pediatric population, that include establishment of standardized data collection procedures across sites for a wide variety of data types, establishment of equipoise, and approaches for minimizing unblinding of selected key personnel. The study framework that was established should provide a useful template for other pediatric controlled studies or other studies that evaluate surgical interventions.

Executive summary of respiratory indications for polysomnography in children: an evidence-based review.

Abstract: Objective This comprehensive, evidence-based review provides a systematic analysis of the literature regarding the validity, reliability, and clinical utility of polysomnography for characterizing breathing during sleep in children. Findings serve as the foundation of practice parameters regarding respiratory indications for polysomnography in children. Methods A task force of content experts performed a systematic review of the relevant literature and graded the evidence using a standardized grading system. Two hundred forty-three evidentiary papers were reviewed, summarized, and graded. The analysis addressed the operating characteristics of polysomnography as a diagnostic procedure in children and identified strengths and limitations of polysomnography for evaluation of respiratory function during sleep. Results The analysis documents strong face validity and content validity, moderately strong convergent validity when comparing respiratory findings with a variety of relevant independent measures, moderate-to-strong test-retest validity, and limited data supporting discriminant validity for characterizing breathing during sleep in children. The analysis documents moderate-to-strong test-retest reliability and interscorer reliability based on limited data. The data indicate particularly strong clinical utility in children with suspected sleep related breathing disorders and obesity, evolving metabolic syndrome, neurological, neurodevelopmental, or genetic disorders, and children with craniofacial syndromes. Specific consideration was given to clinical utility of polysomnography prior to adenotonsillectomy (AT) for confirmation of obstructive sleep apnea syndrome. The most relevant findings include: (1) recognition that clinical history and examination are often poor predictors of respiratory polygraphic findings, (2) preoperative polysomnography is helpful in predicting risk for perioperative complications, and (3) preoperative polysomnography is often helpful in predicting persistence of obstructive sleep apnea syndrome in patients after AT. No prospective studies were identified that address whether clinical outcome following AT for treatment of obstructive sleep apnea is improved in association with routine performance of polysomnography before surgery in otherwise healthy children. A small group of papers confirm the clinical utility of polysomnography for initiation and titration of positive airway pressure support. Conclusions Pediatric polysomnography shows validity, reliability, and clinical utility that is commensurate with most other routinely employed diagnostic clinical tools or procedures. Findings indicate that the "gold standard" for diagnosis of sleep related breathing disorders in children is not polysomnography alone, but rather the skillful integration of clinical and polygraphic findings by a knowledgeable sleep specialist. Future developments will provide more sophisticated methods for data collection and analysis, but integration of polysomnographic findings with the clinical evaluation will represent the fundamental diagnostic challenge for the sleep specialist.

Periodic limb movements and disrupted sleep in children with sickle cell disease.

Abstract: STUDY OBJECTIVES To describe the rate, distribution and correlates of periodic limb movements in sleep (PLMS) in children with sickle cell disease (SCD). DESIGN Prospective, cross-sectional. SETTING Hospital-based sleep laboratory. PARTICIPANTS Sixty-four children aged 2-18 years with SCD, hemoglobin SS-type who had an overnight polysomnogram and a parent-completed Pediatric Sleep Questionnaire. Mean age was 8.4 years (SD 4.8); 50% were male. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS The mean PLMS index was 3.7 (6.6) and ranged from 0 to 31.8, with 23.4% of the sample having PLMS ≥ 5/h. Sleep efficiency was decreased (P = 0.03), and the total arousal index (P = 0.003) and PLMS arousal index (P < 0.001) were increased in children with PLMS ≥ 5/h compared to those with PLMS < 5/h. PLMS were most frequent in NREM stage 2 sleep and during the fourth hour of sleep. Inter-movement interval duration peaked at 25-30 s. "Growing pains worst in bed" or "restlessness of the legs", suggesting restless legs syndrome (RLS), were reported in 12.5% of the total sample and were more common in children with elevated PLMS. A PLMS score for identifying elevated PLMS in children, based on items from the Pediatric Sleep Questionnaire, did not significantly predict PLMS ≥ 5/h. CONCLUSIONS Elevated PLMS are common in children with SCD and are associated with sleep disruption and symptoms of RLS. Future research into the time structure of PLMS, their causes and consequences, and development of a disease-specific sleep disorders screening questionnaire, is needed in children with SCD.

Nocturnal saturation and glucose tolerance in children with cystic fibrosis

Abstract: Background Glucose intolerance is common in cystic fibrosis (CF), and is associated with worsening pulmonary function and nutritional status, and increased mortality. As sleep-disordered breathing is associated with disorders of glucose metabolism, it was hypothesised that recurrent episodes of hypoxaemia during sleep, and sleep disruption, would be associated with inflammation and glucose intolerance in CF. Methods 25 children (aged 14±4 (mean±SD) years) with CF underwent polysomnography, actigraphy, measurement of serum inflammatory markers and oral glucose tolerance testing. Blood glucose area under the curve (AUC), as a cumulative measure of glucose response, was determined. Polysomnography data were compared with retrospective data from 25 healthy controls. Results Forced expiratory volume in 1 s was 92±14% predicted. 24 subjects underwent glucose tolerance testing, of whom 29% had impaired glucose tolerance and 4% had diabetes. The mean nocturnal oxygen saturation correlated negatively with glucose AUC at 120 min (r=−0.49, p=0.015). Partial correlations and regression models including age, body mass index, nocturnal saturation and pulmonary function indicated that nocturnal saturation accounted for the majority of the predictive power for glucose AUC (R 2 =0.24, p=0.001). There were no meaningful relationships between sleep quality, inflammation and glucose tolerance. Conclusions Lower oxyhaemoglobin saturation is associated with worse glucose regulation in children with CF. Further studies are needed to determine whether lower saturation negatively impacts glucose regulation or, alternatively, whether abnormalities in glucose metabolism are an early sign of pulmonary dysfunction.

Pediatric Polysomnography: The Patient and Family Perspective

Abstract: Study Objectives:The gold-standard test used to diagnose childhood obstructive sleep apnea is polysomnography. However, this test requires an overnight stay at a sleep laboratory and the attachment...

Upper Airway Collapsibility During Wakefulness in Children with Sleep Disordered Breathing, as Determined by the Negative Expiratory Pressure Technique

Abstract: STUDY OBJECTIVES Upper airway (UA) collapsibility is a major factor in the pathophysiology of sleep disordered breathing (SDB). We hypothesized that the negative expiratory pressure (NEP) technique could distinguish between normal children and children with SDB even during wakefulness. DESIGN During wakefulness, NEP of -5 and -10 cm H(2)O was applied during expiration in seated and supine positions. UA muscle activity (EMG) was measured using intra-oral electrodes. SETTING Sleep laboratory. PARTICIPANTS Twenty children with snoring, 20 with obstructive sleep apnea syndrome (OSAS), and 20 controls. MEASUREMENTS AND RESULTS The ratio of the area under the expiratory flow-volume curve during NEP compared to tidal breathing (RatioNEP) was calculated. Similarly, EMG area under the curve during NEP as a ratio of baseline was measured (RatioEMG). There were significant differences in RatioNEP between controls and snorers and controls and OSAS, at both pressures, in both the seated and supine positions; P < 0.0001 for all (e.g., RatioNEP at -5 cm H(2)O, seated: 1.8 ± 0.5, 2.1 ± 0.4, and 3.0 ± 0.6 for OSAS, snorers, and controls, respectively). However, no significant differences were found between snorers and OSAS. For RatioEMG, no significant differences were found between groups. CONCLUSIONS RatioNEP distinguishes between normal children and children with SDB, be it snoring or OSAS, indicating that these children have a more collapsible UA even during wakefulness. However, it does not differentiate between snorers and OSAS, highlighting the important role of UA muscle activity during sleep. NEP technique does not elicit a different UA muscle activity response between controls and children with SDB.

Upper airway genioglossal activity in children with sickle cell disease.

Abstract: Study objectives The prevalence of obstructive sleep apnea syndrome (OSAS) in sickle cell disease (SCD) has been reported to be higher than that in the general pediatric population. However, not all subjects with SCD develop OSAS. We hypothesized that SCD patients with OSAS have a blunted neuromuscular response to subatmospheric pressure loads during sleep, making them more likely to develop upper airway collapse. Design Subjects with SCD with and without OSAS underwent pressure-flow measurements during sleep using intraoral surface electrodes to measure genioglossal EMG (EMGgg). Two techniques were applied to decrease the nasal pressure (P(N)) to subatmospheric levels, resulting in an activated and relatively hypotonic upper airway. The area under the curve of the inspiratory EMGgg moving time average was analyzed. EMGgg activity was expressed as a percentage of baseline. Changes in EMGgg in response to decrements in nasal pressure were expressed as the slope of the EMGgg vs. nasal pressure (slope of EMGgg-P(N)). Setting Sleep laboratory. Participants 4 children with SCD and OSAS and 18 children with SCD but without OSAS. Results THE MAJOR FINDINGS OF THIS STUDY WERE: (1) using the activated but not the hypotonic technique, the slope of EMGgg-P(N) was more negative in SCD controls than SCD OSAS; (2) the slope of EMGgg-P(N) was significantly lower using the activated technique compared to the hypotonic technique in SCD controls only; (3) similarly, the critical closing pressure, Pcrit, was more negative using the activated technique than the hypotonic technique in SCD controls but not in SCD OSAS. Conclusion This preliminary study has shown that children with SCD but without OSAS have more prominent upper airway reflexes than children with SCD and OSAS.