Ruth Bradford

Effect of sleep stage on breathing in children with central hypoventilation.

The early literature suggests that hypoventilation in infants with congenital central hypoventilation syndrome (CHS) is less severe during rapid eye movement (REM) than during non-REM (NREM) sleep. However, this supposition has not been rigorously tested, and subjects older than infancy have not been studied. Given the differences in anatomy, physiology, and REM sleep distribution between infants and older children, and the reduced number of limb movements during REM sleep, we hypothesized that older subjects with CHS would have more severe hypoventilation during REM than NREM sleep. Nine subjects with CHS, aged (mean +/- SD) 13 +/- 7 yr, were studied. Spontaneous ventilation was evaluated by briefly disconnecting the ventilator under controlled circumstances. Arousal was common, occurring in 46% of REM vs. 38% of NREM trials [not significant (NS)]. Central apnea occurred during 31% of REM and 54% of NREM trials (NS). Although minute ventilation declined precipitously during both REM and NREM trials, hypoventilation was less severe during REM (drop in minute ventilation of 65 +/- 23%) than NREM (drop of 87 +/- 16%, P = 0.036). Despite large changes in gas exchange during trials, there was no significant change in heart rate during either REM or NREM sleep. We conclude that older patients with CHS frequently have arousal and central apnea, in addition to hypoventilation, when breathing spontaneously during sleep. The hypoventilation in CHS is more severe during NREM than REM sleep. We speculate that this may be due to increased excitatory inputs to the respiratory system during REM sleep.

Ventilatory responses to hypercapnia during wakefulness and sleep in obese adolescents with and without obstructive sleep apnea syndrome.

STUDY OBJECTIVES Abnormal ventilatory drive may contribute to the pathophysiology of the childhood obstructive sleep apnea syndrome (OSAS). Concomitant with the obesity epidemic, more adolescents are developing OSAS. However, few studies have specifically evaluated the obese adolescent group. The authors hypothesized that obese adolescents with OSAS would have a blunted hypercapnic ventilatory response (HCVR) while awake and blunted ventilatory responses to carbon dioxide (CO(2)) during sleep compared with obese and lean adolescents without OSAS. DESIGN CVR was measured during wakefulness. During nonrapid eye movement (NREM) and rapid eye movement (REM) sleep, respiratory parameters and genioglossal electromyogram were measured during CO(2) administration in comparison with room air in obese adolescents with OSAS, obese control study participants, and lean control study participants. SETTING Sleep laboratory. PARTICIPANTS Twenty-eight obese patients with OSAS, 21 obese control study participants, and 37 lean control study participants. RESULTS The obese OSAS and obese control groups had a higher HCVR compared with the lean control group during wakefulness. During both sleep states, all 3 groups had a response to CO(2); however, the obese OSAS group had lower percentage changes in minute ventilation, inspiratory flow, inspiratory time, and tidal volume compared with the 2 control groups. There were no significance differences in genioglossal activity between groups. CONCLUSIONS HCVR during wakefulness is increased in obese adolescents. Obese adolescents with OSAS have blunted ventilatory responses to CO(2) during sleep and do not have a compensatory prolongation of inspiratory time, despite having normal CO(2) responsivity during wakefulness. Central drive may play a greater role than upper airway neuromotor tone in adapting to hypercapnia.

Neurobehavioral functioning in adolescents with and without obesity and obstructive sleep apnea.

STUDY OBJECTIVES Children and adults with obstructive sleep apnea syndrome (OSAS) exhibit neurobehavioral abnormalities, but few studies have evaluated the transitional stage of adolescence. Obesity is also associated with neurobehavioral abnormalities, and many patients with OSAS are obese. However, the confounding effect of obesity on neurobehavioral abnormalities in adolescents with OSAS has not been evaluated. We hypothesized that obese adolescents with OSAS would exhibit more neurobehavioral abnormalities than obese and lean adolescents without OSAS. DESIGN Cross-sectional, case control. SETTING Sleep Center and community. PARTICIPANTS Obese adolescents with OSAS compared to (1) nonsnoring, obese controls without OSAS, and (2) nonobese, nonsnoring controls. INTERVENTIONS Neurobehavioral evaluation. MEASUREMENTS AND RESULTS Obese adolescents with OSAS had significantly worse executive function and attention compared to both obese (P < 0.001) and lean (P < 0.001) controls, and more depression (P = 0.004) and externalizing symptoms than lean controls (P = 0.008). A higher percentage of participants in the OSAS group scored in the clinically abnormal range on executive functioning, attention, sleepiness, and behavioral functioning than lean controls. Mediation analyses indicated that level of sleep apnea significantly mediated the effect of body mass on executive functioning, attention, and behavior. CONCLUSIONS Obese adolescents with OSAS show impaired executive and behavioral function compared to obese and lean controls, and are more likely to score in the clinically abnormal range on measures of neurobehavioral functioning. These results are especially concerning given that the frontal lobe is still developing during this critical age period. We speculate that untreated OSAS during adolescence may lead to significant neurobehavioral deficits in adulthood.

Relationship between Body Fat Distribution and Upper Airway Dynamic Function during Sleep in Adolescents

INTRODUCTION The obstructive sleep apnea syndrome (OSAS) is associated with increased visceral adipose tissue (VAT) in adults; however, few studies have evaluated VAT in relation to upper airway function in adolescents. We hypothesized that increased neck circumference (NC) and VAT would be associated with increased upper airway collapsibility. METHODS Adolescents (24 obese patients with OSAS, 22 obese control patients, and 29 lean control patients) underwent abdominal magnetic resonance imaging, and measurement of upper airway pressure-flow relationships in the activated and hypotonic upper airway states. RESULTS Patients with OSAS had a greater activated slope of the pressure-flow relationship (SPF) than control groups (P < 0.001), whereas hypotonic SPF was greater in both obese groups compared with lean control patients (P = 0.01). NC and VAT were greater in obese control patients and those with OSAS than in lean control patients (P < 0.001), but did not differ between obese patients with OSAS and obese control patients. In lean control patients and those with OSAS, increased NC was associated with increased activated SPF, whereas in obese control patients it was associated with decreased activated SPF (P = 0.03). In contrast, increased NC was associated with increased hypotonic SPF in all groups (P < 0.001). There was no significant effect of VAT on either activated or hypotonic SPF for any of the three groups. CONCLUSIONS Increased neck circumference was associated with increased upper airway collapsibility in adolescents in the hypotonic but not activated state. These data suggest that obese adolescents without OSAS, despite a narrowed upper airway from adipose tissue, are protected from developing OSAS by upper airway neuromotor activation. Neither neck circumference nor visceral adipose tissue is useful in predicting upper airway collapsibility in obese adolescents.

Anthropometric predictors of visceral adiposity in normal‐weight and obese adolescents

Obesity and fat distribution patterns [subcutaneous vs. visceral adipose tissue (VAT)] are important predictors of future cardiometabolic risk. As accurate VAT measurement entails imaging, surrogate anthropometric measurements that would be cheaper and quicker to obtain would be highly desirable. Sagittal abdominal diameter (SAD) may be better than other VAT surrogate measures in adults, but the value of SAD to predict magnetic resonance imaging (MRI)‐determined VAT in adolescents of different races, sexes, and pubertal stages has not been determined.

Cortical Processing of Respiratory Occlusion Stimuli in Children with Central Hypoventilation Syndrome

RATIONALE The ability of patients with central hypoventilation syndrome (CHS) to produce and process mechanoreceptor signals is unknown. OBJECTIVES Children with CHS hypoventilate during sleep, although they generally breathe adequately during wakefulness. Previous studies suggest that they have compromised central integration of afferent stimuli, rather than abnormal sensors or receptors. Cortical integration of afferent mechanical stimuli caused by respiratory loading or upper airway occlusion can be tested by measuring respiratory-related evoked potentials (RREPs). We hypothesized that patients with CHS would have blunted RREP during both wakefulness and sleep. METHODS RREPs were produced with multiple upper airway occlusions and were obtained during wakefulness, stage 2, slow-wave, and REM sleep. Ten patients with CHS and 20 control subjects participated in the study, which took place at the Childrens Hospital of Philadelphia. Each patient was age- and sex-matched to two control subjects. Wakefulness data were collected from 9 patients and 18 control subjects. MEASUREMENTS AND MAIN RESULTS During wakefulness, patients demonstrated reduced Nf and P300 responses compared with control subjects. During non-REM sleep, patients demonstrated a reduced N350 response. In REM sleep, patients had a later P2 response. CONCLUSIONS CHS patients are able to produce cortical responses to mechanical load stimulation during both wakefulness and sleep; however, central integration of the afferent signal is disrupted during wakefulness, and responses during non-REM are damped relative to control subjects. The finding of differences between patients and control subjects during REM may be due to increased intrinsic excitatory inputs to the respiratory system in this state.

The obstructive sleep apnoea syndrome in adolescents

Background The obstructive sleep apnoea syndrome (OSAS) results from a combination of structural and neuromotor factors; however, the relative contributions of these factors have not been studied during the important developmental phase of adolescence. We hypothesised that adenotonsillar volume (ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway electromyographic response to subatmospheric pressure and the ventilatory response to CO2 during sleep would be major predictors of OSAS risk. Methods 42 obese adolescents with OSAS and 37 weight-matched controls underwent upper airway MRI, measurements of Pcrit, genioglossal electromyography and ventilatory response to CO2 during wakefulness and sleep. Results ATV, NPAV, activated and hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO2 during sleep were all associated with OSAS risk. Multivariate models adjusted for age, gender, body mass index and race indicated that ATV, NPAV and activated Pcrit each independently affected apnoea risk in adolescents; genioglossal electromyography was independently associated in a reduced sample. There was significant interaction between NPAV and activated Pcrit (p=0.021), with activated Pcrit more strongly associated with OSAS in adolescents with larger NPAVs and NPAV more strongly associated with OSAS in adolescents with more negative activated closing pressure. Conclusions OSAS in adolescents is mediated by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated Pcrit). This may have important implications for the management of OSAS in adolescents.

Evolution of Obstructive Sleep Apnea in Infants with Cleft Palate and Micrognathia

STUDY OBJECTIVES Children with craniofacial anomalies are a heterogeneous group at high risk for obstructive sleep apnea (OSA). However, the prevalence and structural predictors of OSA in this population are unknown. We hypothesized that infants with micrognathia would have more significant OSA than those with isolated cleft palate ± cleft lip (ICP), and those with ICP would have more significant OSA than controls. We postulated that OSA severity would correlate with reduced mandibular size, neurodevelopmental scores, and growth. METHODS Prospective cohort study. 15 infants with ICP, 19 with micrognathia, and 9 controls were recruited for polysomnograms, neurodevelopmental testing, cephalometrics (ICP and micrognathia groups) at baseline and a follow-up at 6 mo. RESULTS Baseline apnea-hypopnea index (AHI) [median (range)] of the micrognathia group [20.1 events/h (0.8, 54.7)] was greater than ICP [3.2 (0.3, 30.7)] or controls [3.1 (0.5, 23.3)] (p = 0.001). Polysomnographic findings were similar between ICP and controls. Controls had a greater AHI than previously reported in the literature. Cephalometric measures of both midface hypoplasia and micrognathia correlated with OSA severity. Neurodevelopment was similar among groups. OSA improved with growth in participants with ICP and postoperatively in infants with micrognathia. CONCLUSIONS Micrognathia, but not ICP, was associated with more significant OSA compared to controls. Both midface and mandibular hypoplasia contribute to OSA in these populations. OSA improved after surgical correction in most infants with micrognathia, and improved without intervention before palate repair in infants with ICP.