Raanan Arens

A randomized trial of adenotonsillectomy for childhood sleep apnea.

BACKGROUND Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome, yet its usefulness in reducing symptoms and improving cognition, behavior, quality of life, and polysomnographic findings has not been rigorously evaluated. We hypothesized that, in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation, early adenotonsillectomy, as compared with watchful waiting with supportive care, would result in improved outcomes. METHODS We randomly assigned 464 children, 5 to 9 years of age, with the obstructive sleep apnea syndrome to early adenotonsillectomy or a strategy of watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were assessed at baseline and at 7 months. RESULTS The average baseline value for the primary outcome, the attention and executive-function score on the Developmental Neuropsychological Assessment (with scores ranging from 50 to 150 and higher scores indicating better functioning), was close to the population mean of 100, and the change from baseline to follow-up did not differ significantly according to study group (mean [±SD] improvement, 7.1±13.9 in the early-adenotonsillectomy group and 5.1±13.4 in the watchful-waiting group; P=0.16). In contrast, there were significantly greater improvements in behavioral, quality-of-life, and polysomnographic findings and significantly greater reduction in symptoms in the early-adenotonsillectomy group than in the watchful-waiting group. Normalization of polysomnographic findings was observed in a larger proportion of children in the early-adenotonsillectomy group than in the watchful-waiting group (79% vs. 46%). CONCLUSIONS As compared with a strategy of watchful waiting, surgical treatment for the obstructive sleep apnea syndrome in school-age children did not significantly improve attention or executive function as measured by neuropsychological testing but did reduce symptoms and improve secondary outcomes of behavior, quality of life, and polysomnographic findings, thus providing evidence of beneficial effects of early adenotonsillectomy. (Funded by the National Institutes of Health; CHAT ClinicalTrials.gov number, NCT00560859.).

Adenotonsillectomy outcomes in treatment of obstructive sleep apnea in children: a multicenter retrospective study.

RATIONALE The overall efficacy of adenotonsillectomy (AT) in treatment of obstructive sleep apnea syndrome (OSAS) in children is unknown. Although success rates are likely lower than previously estimated, factors that promote incomplete resolution of OSAS after AT remain undefined. OBJECTIVES To quantify the effect of demographic and clinical confounders known to impact the success of AT in treating OSAS. METHODS A multicenter collaborative retrospective review of all nocturnal polysomnograms performed both preoperatively and postoperatively on otherwise healthy children undergoing AT for the diagnosis of OSAS was conducted at six pediatric sleep centers in the United States and two in Europe. Multivariate generalized linear modeling was used to assess contributions of specific demographic factors on the post-AT obstructive apnea-hypopnea index (AHI). MEASUREMENTS AND MAIN RESULTS Data from 578 children (mean age, 6.9 +/- 3.8 yr) were analyzed, of which approximately 50% of included children were obese. AT resulted in a significant AHI reduction from 18.2 +/- 21.4 to 4.1 +/- 6.4/hour total sleep time (P < 0.001). Of the 578 children, only 157 (27.2%) had complete resolution of OSAS (i.e., post-AT AHI <1/h total sleep time). Age and body mass index z-score emerged as the two principal factors contributing to post-AT AHI (P < 0.001), with modest contributions by the presence of asthma and magnitude of pre-AT AHI (P < 0.05) among nonobese children. CONCLUSIONS AT leads to significant improvements in indices of sleep-disordered breathing in children. However, residual disease is present in a large proportion of children after AT, particularly among older (>7 yr) or obese children. In addition, the presence of severe OSAS in nonobese children or of chronic asthma warrants post-AT nocturnal polysomnography, in view of the higher risk for residual OSAS.

Childhood obesity and obstructive sleep apnea syndrome

The increasing prevalence of obesity in children seems to be associated with an increased prevalence of obstructive sleep apnea syndrome (OSAS) in children. Possible pathophysiological mechanisms contributing to this association include the following: adenotonsillar hypertrophy due to increased somatic growth, increased critical airway closing pressure, altered chest wall mechanics, and abnormalities of ventilatory control. However, the details of these mechanisms and their interactions have not been elucidated. In addition, obesity and OSAS are both associated with metabolic syndrome, which is a constellation of features such as hypertension, insulin resistance, dyslipidemia, abdominal obesity, and prothrombotic and proinflammatory states. There is some evidence that OSAS may contribute to the progression of metabolic syndrome with a potential for significant morbidity. The treatment of OSAS in obese children has not been standardized. Adenotonsillectomy is considered the primary intervention followed by continuous positive airway pressure treatment if OSAS persists. Other methods such as oral appliances, surgery, positional therapy, and weight loss may be beneficial for individual subjects. The present review discusses these issues and suggests an approach to the management of obese children with snoring and possible OSAS.

Diagnostic issues in pediatric obstructive sleep apnea.

Obstructive sleep apnea syndrome (OSAS) in children includes a spectrum of respiratory disorders with significant morbidities. Diagnosis of OSAS is based on clinical suspicion, history, and physical findings, and confirmation is made by polysomnography. There has been significant progress in recent years in technologies available for diagnosis of OSAS since the consensus statement of the American Thoracic Society in 1996. The current review describes methodologies that are available today for assessment and diagnosis of OSAS in children and summarizes the most recent recommendations of the American Academy of Sleep Medicine Task Force regarding scoring sleep-related respiratory events in children.

Sleep-disordered Breathing in Hispanic/Latino Individuals of Diverse Backgrounds. The Hispanic Community Health Study/Study of Latinos

RATIONALE Hispanic/Latino populations have a high prevalence of cardiovascular risk factors and may be at risk for sleep-disordered breathing (SDB). An understanding of SDB among these populations is needed given evidence that SDB increases cardiovascular risk. OBJECTIVES To quantify SDB prevalence in the U.S. Hispanic/Latino population and its association with symptoms, risk factors, diabetes, and hypertension; and to explore variation by sex and Hispanic/Latino background. METHODS Cross-sectional analysis from the baseline examination of the Hispanic Community Health Study/Study of Latinos. MEASUREMENTS AND MAIN RESULTS The apnea-hypopnea index (AHI) was derived from standardized sleep tests; diabetes and hypertension were based on measurement and history. The sample of 14,440 individuals had an age-adjusted prevalence of minimal SDB (AHI ≥ 5), moderate SDB (AHI ≥ 15), and severe SDB (AHI ≥ 30) of 25.8, 9.8, and 3.9%, respectively. Only 1.3% of participants reported a sleep apnea diagnosis. Moderate SDB was associated with being male (adjusted odds ratio, 2.7; 95% confidence interval, 2.3-3.1), obese (16.8; 11.6-24.4), and older. SDB was associated with an increased adjusted odds of impaired glucose tolerance (1.7; 1.3-2.1), diabetes (2.3; 1.8-2.9), and hypertension. The association with hypertension varied across background groups with the strongest associations among individuals of Puerto Rican and Central American background. CONCLUSIONS SDB is prevalent in U.S. Latinos but rarely associated with a clinical diagnosis. Associations with diabetes and hypertension suggest a large burden of disease may be attributed to untreated SDB, supporting the development and evaluation of culturally relevant detection and treatment approaches.

Upper airway structure and body fat composition in obese children with obstructive sleep apnea syndrome.

RATIONALE Mechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood. OBJECTIVES The aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS. METHODS Magnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS. MEASUREMENTS AND MAIN RESULTS We studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues. CONCLUSIONS Upper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.

Periodic limb movement in sleep in children with Williams syndrome

OBJECTIVE Williams syndrome (WS) is associated with neurobehavioral abnormalities that include irritability and attention-deficit/hyperactivity disorder. Parents often report children having difficulties initiating and maintaining sleep because of restlessness and arousals. Therefore we evaluated a group of children with WS for the presence of a movement arousal sleep disorder. METHODS Twenty-eight families of children with WS participated in a telephone survey aimed to screen for a movement arousal disorder. Of the 16 children identified as having such a disorder, 7 (mean age, 3.9 +/- 2.2 years) underwent polysomnography. Their studies were compared with those of 10 matched control subjects (mean age, 5.3 +/- 2.0 years). RESULTS The 7 subjects with WS who were screened by the survey had sleep latency, total sleep time, arousals, and awakenings that were similar to those of control subjects. However, they presented with a disorder of periodic limb movement in sleep (PLMS). The PLMS index in the subjects with WS was 14.9 +/- 6.2 versus 2.8 +/- 1.9 in control subjects (P < .0001). In addition, arousal and awakening in subjects with WS were strongly associated with PLMS. Moreover, children with WS spend more time awake during sleep periods than control subjects (10.0% +/- 7.0% vs 4.4% +/- 4.7%; P < .05). Five children were treated with clonazepam, and in 4 a significant clinical response was noted. CONCLUSION We report an association between WS and PLMS. Clonazepam may reduce the clinical symptoms of PLMS in some of these children.

Obesity-Associated Asthma in Children: A Distinct Entity

BACKGROUND Obesity-associated asthma has been proposed to be a distinct entity, differing in immune pathogenesis from atopic asthma. Both obesity-mediated inflammation and increase in adiposity are potential mechanistic factors that are poorly defined among children. We hypothesized that pediatric obesity-associated asthma would be characterized by T helper (Th) 1, rather than the Th2 polarization associated with atopic asthma. Moreover, we speculated that Th1 biomarkers and anthropometric measures would correlate with pulmonary function tests (PFTs) in obese asthmatic children. METHODS We recruited 120 children, with 30 in each of the four study groups: obese asthmatic children, nonobese asthmatic children, obese nonasthmatic children, and nonobese nonasthmatic children. All children underwent pulmonary function testing. Blood was collected for measurement of serum cytokines. T-cell responses to mitogen, phorbol 12-myristate 13-acetate (PMA), or antigens tetanus toxoid or Dermatophagoides farinae were obtained by flow cytometric analysis of intracellular cytokine staining for interferon-γ (IFN-γ) (Th1) or IL-4 (Th2) within the CD4 population. RESULTS Obese asthmatic children had significantly higher Th1 responses to PMA (P < .01) and tetanus toxoid (P < .05) and lower Th2 responses to PMA (P < .05) and D farinae (P < .01) compared with nonobese asthmatic children. Th-cell patterns did not differ between obese asthmatic children and obese nonasthmatic children. Obese asthmatic children had lower FEV(1)/FVC (P < .01) and residual volume/total lung capacity ratios (P < .005) compared with the other study groups, which negatively correlated with serum interferon-inducible protein 10 and IFN-γ levels, respectively. PFTs, however, did not correlate with BMI z score or waist to hip ratio. CONCLUSIONS We found that pediatric obesity-associated asthma differed from atopic asthma and was characterized by Th1 polarization. The altered immune environment inversely correlated with PFTs in obese asthmatic children.

Sleep and Periodic Limb Movement in Sleep in Juvenile Fibromyalgia

Objectives. Fibromyalgia has been recently recognized in children and adolescents as juvenile fibromyalgia (JF). In adult fibromyalgia, subjective complaints of nonrestorative sleep and fatigue are supported by altered polysomnographic findings including a primary sleep disorder known as periodic limb movements in sleep (PLMS) in some subjects. Although poor sleep is a diagnostic criterion for JF, few reports in the literature have evaluated specific sleep disturbances. Our objectives were to evaluate in a controlled study the polysomnographic findings of children and adolescents with JF for alterations in sleep architecture as well as possible PLMS not previously noted in this age group. Methods. Sixteen consecutive children and adolescents (15.0 ± 2.6 years of age) diagnosed with JF underwent overnight polysomnography. Polysomnography was also performed on 14 controls (14.0 ± 2.2 years of age) with no history of an underlying medical condition that could impact on sleep architecture. Respiratory variables, sleep stages, and limb movements were measured during sleep in all subjects. Results. JF subjects differed significantly from controls in sleep architecture. JF subjects presented with prolonged sleep latency, shortened total sleep time, decreased sleep efficiency, and increased wakefulness during sleep. In addition, JF subjects exhibited excessive movement activity during sleep. Six of the JF subjects (38%) were noted to have an abnormally elevated PLMS index (>5/hour), indicating PLMS in these subjects. Conclusion. Our study demonstrated abnormalities in sleep architecture in children with JF. We also noted PLMS in a significant number of subjects. This has not been reported previously in children with this disorder. We recommend that children who are evaluated for JF undergo polysomnography including PLMS assessment. juvenile fibromyalgia; periodic limb movement in sleep; restless legs syndrome.

Effect of Lateral Positioning on Upper Airway Size and Morphology in Sedated Children

Background:Lateral positioning decreases upper airway obstruction in paralyzed, anesthetized adults and in individuals with sleep apnea during sleep. The authors hypothesized that lateral positioning increases upper airway cross-sectional area and total upper airway volume when compared with the supine position in sedated, spontaneously breathing children. Methods:Children aged 2–12 yr requiring magnetic resonance imaging examination of the head or neck region using deep sedation with propofol were studied. Exclusion criteria included any type of anatomical or neurologic entity that could influence upper airway shape or size. T1 axial scans of the upper airway were obtained in the supine and lateral positions, with the head and neck axes maintained neutral. Using software based on fuzzy connectedness segmentation (3D-VIEWNIX; Medical Imaging Processing Group, University of Pennsylvania, Philadelphia, PA), the magnetic resonance images were processed and segmented to render a three-dimensional reconstruction of the upper airway. Total airway volumes and cross-sectional areas were computed between the nasal vomer and the vocal cords. Two-way paired t tests were used to compare airway sizes between supine and lateral positions. Results:Sixteen of 17 children analyzed had increases in upper airway total volume. The total airway volume (mean ± SD) was 6.0 ± 2.9 ml3 in the supine position and 8.7 ± 2.5 ml3 in the lateral position (P < 0.001). All noncartilaginous areas of the upper airway increased in area in the lateral compared with the supine position. The region between the tip of the epiglottis and vocal cords demonstrated the greatest relative percent change. Conclusions:The upper airway of a sedated, spontaneously breathing child widens in the lateral position. The region between the tip of the epiglottis and the vocal cords demonstrates the greatest relative percent increase in size.