Nocturnal oximetry in children with obstructive lung disease or sleep-disordered breathing.

OBJECTIVES: Although progress has been made in the standardized interpretation of nocturnal oximetry in children with obstructive sleep-disordered breathing (SDB), no evidence exists on oximetry abnormalities in other respiratory disorders. We aimed to compare obstructive lung disease (OLD) and SDB regarding nocturnal oximetry parameters. METHODS: We analyzed oximetry recordings from children with (i) OLD (obliterative bronchiolitis; cystic fibrosis); (ii) snoring and adenotonsillar hypertrophy (SDB); and (iii) no respiratory disorder (controls). The three groups were compared regarding: (i) oxygen desaturation of hemoglobin index (SpO2 drops ≥3%/h-ODI3) and (ii) basal SpO2 (average SpO2 between SpO2 drops). The associations of oximetry parameters (natural logarithm) with study group were tested using linear regression including age as covariate. RESULTS: Data of 16 subjects with OLD (median age: 7.3 years; Q25, Q75: 5.4, 12), 22 children with SDB (6.3 years; 4, 9) and 22 controls (6.8 years; 5.6, 10.3) were analyzed. Children with OLD or SDB had significantly lower basal SpO2 than controls (91.9% [90.8, 93.4] vs 96.3% [96, 97.4] vs 97.6% [97.1, 97.9]; P < 0.01). No subjects in the SDB or control groups had basal SpO2 < 95%. Children with SDB had significantly higher ODI3 than children with OLD or controls [8.4 episodes/h (6.2, 16.6) vs 4.4 episodes/h (3.6, 6.6) vs 2 episodes/h (1.3, 2.7); P < 0.01]. OLD had the greatest negative effect on basal SpO2 (R2 = 0.62; P < 0.001) and SDB the greatest positive effect on ODI3 (R2 = 0.34; P < 0.001). CONCLUSION: OLD is associated mostly with reduced basal SpO2 , whereas SDB is characterized by elevated ODI3.

Obstructive events in children with Prader-Willi syndrome occur predominantly during rapid eye movement sleep.

OBJECTIVE: Children with Prader-Willi syndrome (PWS) have a high prevalence of obstructive sleep apnea syndrome (OSAS). In most typically developing children with OSAS, more obstructive apneas and hypopneas occur during rapid eye movement (REM) than during non-REM (NREM) sleep. It was hypothesized that patients with PWS are even more prone to obstructive events in REM sleep than otherwise healthy subjects with OSAS. METHODS: Polysomnographic data of patients with PWS and of typically developing children (controls) with OSAS (apnea-hypopnea index [AHI] > 1 episode/h) were analyzed. The two groups were compared regarding obstructive AHI (OAHI), OAHI during NREM sleep (OAHInrem), OAHI during REM sleep (OAHIrem), and the OAHIrem/OAHI ratio (outcome measures). The association between PWS diagnosis and OAHIrem/OAHI was adjusted for confounders using a general linear model. RESULTS: Twelve children with PWS (median age 7.1 years [interquartile range 3.5, 12.4 years]) and 53 controls (6.5 years [3.9, 8.7 years]) were studied. Children with PWS and controls were similar regarding OAHI (p = 0.21) and OAHInrem (p = 0.76). However, subjects with PWS had higher OAHIrem (17.6 episodes/h [5.8, 25.8 episodes/h]) and OAHIrem/OAHI (2.3 [1.5, 3.2]) than controls (5 episodes/h [1.5, 8.1 episodes/h]; p = 0.002 and 1 [0.5, 2]; p = 0.003, respectively). The association between PWS diagnosis and higher OAHIrem/OAHI persisted after adjustment for age, gender, and obesity (p = 0.009). CONCLUSION: In children with PWS, OAHI calculated for total sleep time does not reflect OSAS severity during REM sleep, which on average can be twice as high. Mild OSAS in patients with PWS demonstrated by polygraphy without sleep staging may correspond to a moderately-to-severely increased OAHIrem.

ERS statement on obstructive sleep disordered breathing in 1- to 23-month-old children.

The present statement was produced by a European Respiratory Society Task Force to summarise the evidence and current practice on the diagnosis and management of obstructive sleep disordered breathing (SDB) in children aged 1-23 months. A systematic literature search was completed and 159 articles were summarised to answer clinically relevant questions. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are identified. Morbidity (pulmonary hypertension, growth delay, behavioural problems) and coexisting conditions (feeding difficulties, recurrent otitis media) may be present. SDB severity is measured objectively, preferably by polysomnography, or alternatively polygraphy or nocturnal oximetry. Children with apparent upper airway obstruction during wakefulness, those with abnormal sleep study in combination with SDB symptoms (e.g. snoring) and/or conditions predisposing to SDB (e.g. mandibular hypoplasia) as well as children with SDB and complex conditions (e.g. Down syndrome, Prader-Willi syndrome) will benefit from treatment. Adenotonsillectomy and continuous positive airway pressure are the most frequently used treatment measures along with interventions targeting specific conditions (e.g. supraglottoplasty for laryngomalacia or nasopharyngeal airway for mandibular hypoplasia). Hence, obstructive SDB in children aged 1-23 months is a multifactorial disorder that requires objective assessment and treatment of all underlying abnormalities that contribute to upper airway obstruction during sleep.

When and why to treat the child who snores?

Obstructive sleep-disordered breathing (SDB) can result in cardiovascular and neurocognitive morbidity as well as adversely affect behavior, growth, quality of life, and nocturnal continence. This article summarizes the latest evidence regarding the morbidity related to obstructive SDB, commenting on the impact of severity of obstruction, that is, the difference in effects seen of moderate to severe obstructive sleep apnea syndrome (OSAS) compared to those of mild OSAS or primary snoring. The impact of therapy is discussed, focusing on which children are likely to benefit from treatment interventions; namely those with moderate or severe OSAS irrespective of the presence of morbidity, children with mild OSAS with associated morbidity or predictors of SDB persistence such as obesity, and children with complex conditions accompanied by upper airway obstruction like craniosynostosis and Prader-Willi syndrome. The co-existing conditions which may improve when treatment for obstructive SDB is offered are reviewed, while the clinical parameters associated with spontaneous improvement or resolution of obstructive SDB are discussed. The intention being to enable clinicians to make informed decisions on who should be treated, when and why. Pediatr Pulmonol. 2017;52:399-412. © 2016 Wiley Periodicals, Inc.

Obstructive sleep disordered breathing in 2- to 18-year-old children: diagnosis and management.

This document summarises the conclusions of a European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood and refers to children aged 2-18 years. Prospective cohort studies describing the natural history of SDB or randomised, double-blind, placebo-controlled trials regarding its management are scarce. Selected evidence (362 articles) can be consolidated into seven management steps. SDB is suspected when symptoms or abnormalities related to upper airway obstruction are present (step 1). Central nervous or cardiovascular system morbidity, growth failure or enuresis and predictors of SDB persistence in the long-term are recognised (steps 2 and 3), and SDB severity is determined objectively preferably using polysomnography (step 4). Children with an apnoea-hypopnoea index (AHI) >5 episodes·h(-1), those with an AHI of 1-5 episodes·h(-1) and the presence of morbidity or factors predicting SDB persistence, and children with complex conditions (e.g. Down syndrome and Prader-Willi syndrome) all appear to benefit from treatment (step 5). Treatment interventions are usually implemented in a stepwise fashion addressing all abnormalities that predispose to SDB (step 6) with re-evaluation after each intervention to detect residual disease and to determine the need for additional treatment (step 7).

Expression of leukotriene biosynthetic enzymes in tonsillar tissue of children with obstructive sleep apnea: a prospective nonrandomized study.

IMPORTANCE: Cysteinyl leukotrienes (CysLTs) potentially promote adenotonsillar hypertrophy in children with obstructive sleep apnea (OSA). Previous studies have identified CysLTs and their receptors in tonsillar tissue from children with OSA. OBJECTIVE: To demonstrate expression of the leukotriene biosynthetic enzymes 5-lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP), leukotriene A(4) hydrolase (LTA(4)H), and leukotriene C(4) synthase (LTC(4)S) in T and B tonsillar lymphocytes from pediatric patients with OSA. It was hypothesized that children with OSA have greater expression of biosynthetic enzymes for CysLTs (5-LO, FLAP, and LTC(4)S) in their tonsillar tissue than do children with recurrent tonsillitis (RT), who were enrolled as controls. DESIGN, SETTING, AND PARTICIPANTS: This prospective, nonrandomized study was performed at a tertiary care university hospital on 13 children with OSA and adenotonsillar hypertrophy undergoing adenotonsillectomy and 12 children without OSA also undergoing tonsillectomy for RT. Tonsillar tissue from children with OSA or RT was examined for 5-LO, FLAP, LTA(4)H, and LTC(4)S expression under real time-quantitative polymerase chain reaction (RT-qPCR), flow cytometry (FC), and confocal laser scanning microscopy (CM). MAIN OUTCOMES AND MEASURES: Expression of biosynthetic enzymes for CysLTs (5-LO, FLAP, and LTC(4)S) was the main outcome measure. Patients with OSA and control patients with RT were compared for numbers of copies of 5-LO, FLAP, and LTC(4)S messenger RNA (by RT-qPCR) in T or B tonsillar lymphocytes and proportions of CD3(+) or CD19(+) tonsillar lymphocytes that expressed 5-LO, FLAP, and LTC(4)S (by FC). RESULTS: Messenger RNA for all 4 enzymes was detected in T and B lymphocytes from both study groups, and expression of all biosynthetic enzymes was demonstrated in participants with OSA and RT by FC. Patients with OSA differed from controls in the proportions (median [10th-90th percentile]) of LTC(4)S(+) CD3(+) T lymphocytes (23.31% [8.64%-50.07%] vs 10.81% [3.48%-23.32%], respectively) (P = .01) and LTC(4)S(+) CD19(+) B lymphocytes (20.66% [14.62%-65.77%] vs 12.53% [2.87%-36.64%], respectively) (P = .01) detected by FC. Immunoreactivity for the 4 enzymes was detected by CM in B lymphocytes of mantle zones and T lymphocytes of extrafollicular areas. CONCLUSIONS AND RELEVANCE: Leukotriene biosynthetic enzymes are expressed in tonsillar lymphocytes, and the previously reported detection of CysLTs in tonsillar tissue from children with OSA may be attributed to endogenous synthesis. Enhanced expression of LTC(4)S is a potential target for pharmacologic interventions in OSA.

Poincaré plot width, morning urine norepinephrine levels, and autonomic imbalance in children with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) in childhood is accompanied by sympathetic overflow unopposed by the parasympathetic tone. Complex methods like power spectral analysis of heart rate variability have been applied to study this imbalance. In this report, width of Poincaré scattergram of the R-R interval (parasympathetic tone) and morning urine norepinephrine concentration (sympathetic activity) were used to assess autonomic imbalance. METHODS: Poincaré plot was obtained from the electrocardiographic channel of nocturnal polysomnography and its width was measured, and norepinephrine-to-creatinine concentration ratio was calculated in morning urine specimen. RESULTS: Twenty children with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia (oxygen saturation of hemoglobin [SpO(2)] nadir <90%), 24 subjects with mild hypoxemia (SpO(2) nadir ≥90%), and 11 control subjects were recruited. Children with obstructive sleep apnea and moderate-to-severe hypoxemia had significantly narrower Poincaré plot width (318.7 ± 139.3 ms) and higher ln-transformed urine norepinephrine-to-creatinine ratio (4.5 ± 0.6) than control subjects (484.2 ± 104.4 ms and 3.8 ± 0.4, respectively; P < 0.05). Ln-transformed urine norepinephrine levels were inversely related to Poincaré plot width (P = 0.02). CONCLUSIONS: Subjects with obstructive sleep apnea and moderate-to-severe nocturnal hypoxemia have enhanced sympathetic activity and reduced parasympathetic drive. Poincaré plot width and urine norepinephrine levels are simple measures of autonomic imbalance in pediatric obstructive sleep apnea.

Insomnia symptoms, objective sleep duration and hypothalamic-pituitary-adrenal activity in children.

BACKGROUND: Insomnia symptoms are the most common parent-reported sleep complaints in children; however, little is known about the pathophysiology of childhood insomnia symptoms, including their association with hypothalamic-pituitary-adrenal (HPA) axis activation. The objective of this study is to examine the association between parent-reported insomnia symptoms, objective short sleep duration and cortisol levels in a population-based sample of school-aged children. DESIGN: A sample of 327 children from the Penn State Child Cohort (5-12 years old) underwent 9-h overnight polysomnography and provided evening and morning saliva samples to assay for cortisol. Objective short sleep duration was defined based on the median total sleep time (i.e., <7·7 h). Parent-reported insomnia symptoms of difficulty initiating and/or maintaining sleep were ascertained with the Pediatric Behavior Scale. RESULTS: Children with parent-reported insomnia symptoms and objective short sleep duration showed significantly increased evening (0·33±0·03 µg/dL) and morning (1·38±0·08 µg/dL) cortisol levels. In contrast, children with parent-reported insomnia symptoms and 'normal' sleep duration showed similar evening and morning cortisol levels (0·23±0·03 µg/dL and 1·13±0·08 µg/dL) compared with controls with 'normal' (0·28±0·02 µg/dL and 1·10±0·04 µg/dL) or short (0·28±0·02 µg/dL and 1·13±0·04 µg/dL) sleep duration. CONCLUSIONS: Our findings suggest that insomnia symptoms with short sleep duration in children may be related to 24-h basal or responsive physiological hyperarousal. Future studies should explore the association of insomnia symptoms with short sleep duration with physical and mental health morbidity.

Sleep apnoea, sleepiness, inflammation and insulin resistance in middle-aged males and females.

In obese males obstructive sleep apnoea (OSA) is associated with inflammation and insulin resistance; however, findings are confounded by adipose tissue, a hormone- and cytokine-secreting organ. Our goal was to examine whether in a relatively nonobese population, OSA is associated with sleepiness and inflammation/insulin resistance, and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (CPAP) use. 77 subjects, 38 middle-aged males and post-menopausal females with OSA and 39 male and female controls, were studied in the sleep laboratory for 4 nights. Measures of sleepiness (objective and subjective), performance, serial 24-h blood samples for interleukin (IL)-6, tumour necrosis factor receptor (TNFR)-1, leptin and adiponectin, and single samples for high-sensitivity C-reactive protein (hsCRP), fasting glucose and insulin levels were obtained. Apnoeic males were significantly sleepier and had significantly higher hsCRP, IL-6, leptin and insulin resistance than controls. Apnoeic females had significantly higher hsCRP; however, objective sleepiness, IL-6, TNFR-1, insulin resistance (Homeostatic Model Assessment index), leptin and adiponectin were similar to controls. CPAP improved subjective sleepiness, but no changes were observed in any of the biomarkers. In conclusion, OSA is associated with sleepiness, inflammation and insulin resistance, even in nonobese males, and this association is stronger in males than in females. Short-term CPAP does not improve the inflammatory/metabolic aberrations in OSA.

Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance.

One workweek of mild sleep restriction adversely impacts sleepiness, performance, and proinflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation, and stress hormones, 30 healthy young men and women (mean age ± SD, 24.7 ± 3.5 yr; mean body mass index ± SD, 23.6 ± 2.4 kg/m(2)) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8 h/night), followed by 6 sleep restriction nights (6 h/night) and 3 recovery nights (10 h/night)]. Twenty-four-hour profiles of circulating IL-6 and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after 1 wk of sleep restriction), and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared with baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one work week of mild sleep restriction on daytime sleepiness, fatigue, and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.