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.

Understanding the anatomic basis for obstructive sleep apnea syndrome in adolescents.

RATIONALE: Structural risk factors for obstructive sleep apnea syndrome (OSAS) in adolescents have not been well characterized. Because many adolescents with OSAS are obese, we hypothesized that the anatomic OSAS risk factors would be more similar to those in adults than those in children. OBJECTIVES: To investigate the anatomic risk factors in adolescents with OSAS compared with obese and lean control subjects using magnetic resonance imaging (MRI). METHODS: Three groups of adolescents (age range: 12-16 yr) underwent MRI: obese individuals with OSAS (n = 49), obese control subjects (n = 38), and lean control subjects (n = 50). MEASUREMENTS AND MAIN RESULTS: We studied 137 subjects and found that (1) obese adolescents with OSAS had increased adenotonsillar tissue compared with obese and lean control subjects; (2) obese OSAS adolescents had a smaller nasopharyngeal airway than control subjects; (3) the size of other upper airway soft tissue structures (volume of the tongue, parapharyngeal fat pads, lateral walls, and soft palate) was similar between subjects with OSAS and obese control subjects; (4) although there were no major craniofacial abnormalities in most of the adolescents with OSAS, the ratio of soft tissue to craniofacial space surrounding the airway was increased; and (5) there were sex differences in the pattern of lymphoid proliferation. CONCLUSIONS: Increased size of the pharyngeal lymphoid tissue, rather than enlargement of the upper airway soft tissue structures, is the primary anatomic risk factor for OSAS in obese adolescents. These results are important for clinical decision making and suggest that adenotonsillectomy should be considered as the initial treatment for OSAS in obese adolescents, a group that has poor continuous positive airway pressure adherence and difficulty in achieving weight loss.

Anthropometric predictors of visceral adiposity in normal-weight and obese adolescents.

BACKGROUND: 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. AIM: To test the hypothesis that SAD correlates more strongly with volumetric VAT than other anthropometric measurements, independent of age, sex, race, and Tanner stage. SUBJECTS AND METHODS: Twenty-eight normal-weight and 44 obese adolescents underwent Tanner staging, anthropometric examinations, and abdominal MRI for volumetric partitioned fat calculation. RESULTS: VAT increased exponentially in the body mass index (BMI) > 97th percentile range. SAD, waist circumference (WC), BMI, and BMI Z-score correlated strongly with VAT (correlation coefficients of 0.85-0.86, all p-values < 0.0005); waist-hip ratio was less predictive of VAT (r = 0.68, p < 0.0005). On hierarchical regression, the strongest predictors of VAT in obese subjects were BMI Z-score and SAD (R(2) = 0.34 vs. 0.31, respectively, p < 0.0005); in normal-weight subjects, most anthropometric measures predicted VAT equally (R(2) = 0.16-0.18, p-values = 0.018-0.026). CONCLUSIONS: Unlike adults, in obese adolescents, SAD is not the strongest predictor of visceral adiposity. BMI Z-score is equivalently predictive and, together with BMI, provides sufficient information to assess visceral adiposity; more specialized anthropometric measurements (e.g., SAD and WC) do not add additional predictive value.

A Trial of Intranasal Corticosteroids to Treat Childhood OSA Syndrome.

BACKGROUND: Intranasal corticosteroids (INCS) are frequently used to treat OSA syndrome (OSAS) in children. However, their efficacy has not been rigorously tested. RESEARCH QUESTION: Do INCS result in improved OSAS symptoms, polysomnography findings, behavior, and quality of life compared with placebo? STUDY DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled trial, children with OSAS aged 5 to 12 years (N = 134) were randomized 2:1 to receive 3 months of INCS or placebo. Children in the INCS arm were then re-randomized to receive 9 months of INCS or placebo. Polysomnography, symptoms, and neurobehavioral findings were measured at baseline, 3 months, and 12 months. The primary outcome was change in obstructive apnea hypopnea index (OAHI) at 3 months, available for 122 children. The secondary outcome was OAHI change at 12 months, available for 70 children. RESULTS: Median (interquartile range) age and OAHI at baseline for the entire group were 7.9 (6.3 to 9.9) years and 5.8 (3.6 to 9.7) events per hour. OAHI changes at 3 months (-1.72 [-3.91 to 1.92] events per hour) and 12 months (-1.2 [-4.22 to 1.71] events per hour) were not different between the two groups (P = not significant). OSAS symptoms and neurobehavioral results did not differ between the INCS and placebo groups at 3 and 12 months. The 38 children who received INCS for 12 months reported a significant OAHI decrease from 7.2 (3.62 to 9.88) events per hour to 3.7 (1.56 to 6.4) events per hour (P = .039). INTERPRETATION: In children with OSAS, treatment with INCS did not result in significant polysomnography, neurobehavioral, or symptom changes at 3 and 12 months of treatment. Twelve months of INCS treatment resulted in a statistically significant but not clinically relevant OAHI reduction. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02180672; URL: www. CLINICALTRIALS: gov.

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 Children's 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.

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.

Upper airway collapsibility and genioglossus activity in adolescents during sleep.

STUDY OBJECTIVES: Obese patients develop obstructive sleep apnea syndrome (OSAS), at least in part because of a narrowed upper airway. However, many obese adolescents do not develop OSAS, despite having a presumably narrower airway. The reasons for this phenomenon are unclear. The authors hypothesized that obese controls have a compensatory neuromuscular response to subatmospheric pressure loads during sleep, making them less likely to develop upper airway collapse. DESIGN: Patients underwent pressure-flow measurements during sleep while wearing intraoral electrodes to measure genioglossal electromyography (EMGgg). Two techniques were applied to decrease nasal pressure (P(N)) to subatmospheric levels, resulting in an activated and relatively hypotonic upper airway. SETTING: Sleep laboratory. PARTICIPANTS: There were 35 obese patients with OSAS, 28 obese controls, and 43 lean controls. RESULTS: In the activated state, the two control groups had a flatter slope of the pressure-flow relationship and a more negative critical closing pressure (less collapsible) than the OSAS group. In the hypotonic state, the lean controls had a flatter slope of the pressure-flow relationship than the OSAS and obese control groups. In the activated state, the slope of EMGgg versus P(N) was greater in the obese control group than in the OSAS or lean control groups (P = 0.002 and P = 0.028, respectively); there were no differences in the hypotonic state. CONCLUSIONS: Obese controls have vigorous upper airway neuromuscular responses during sleep. Upper airway reflexes normally decline during adolescent development. It is speculated that obese adolescents without OSAS maintain protective upper airway reflexes during adolescent development, whereas those who go on to develop OSAS do not.