Respiratory indices during sleep in healthy infants: A prospective longitudinal study and meta-analysis.

STUDY OBJECTIVES: Healthy infants may have a greater apnea hypopnea index (AHI) than older children during the newborn period, but the trajectory of these sleep-related events beyond the first month of life is poorly understood. In this study, we evaluated the longitudinal changes in respiratory indices during sleep in healthy infants during the first six months of life. METHODS: Single-center prospective cohort study. Thirty healthy infants underwent overnight in-lab polysomnography at one and five months of age and findings were compared between assessments. Systematic review of studies evaluating infant polysomnography and meta-analysis was conducted. RESULTS: At one month of age, total AHI, obstructive AHI, and central AHI model-adjusted means (95% confidence interval) were 16.9 events/hour (12.2, 21.5), 10.2 events/hour (7.4, 13.1), and 6.6 events/hour (4.2, 9.0), respectively. 16.8% of events were obstructive apneas and 36.1% central apneas. By five months of age, there were significant reductions in each index to 4.1 events/hour (3.2, 5.0), 1.9 events/hour (1.4, 2.4), and 2.2 events/hour (1.6, 2.9), respectively (p < 0.001 for each), and a lower proportion of events were obstructive apneas (8.6%, p = 0.007) and a greater proportion central apneas (52.3%, p = 0.002). Meta-analysis found high AHI in infants with significant heterogeneity. CONCLUSIONS: Central AHI and obstructive AHI are greater in healthy newborns than older children. There is a significant spontaneous reduction in events and change in type of events in the first six months of life in this low-risk population. These findings may serve as a reference for clinicians evaluating for obstructive sleep apnea in infants.

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.

Upper Airway Vibration Perception in School-Aged Children with Obstructive Sleep Apnea.

STUDY OBJECTIVES: Children with the obstructive sleep apnea (OSA) have impaired upper airway two-point discrimination compared to controls. In addition, blunted vibration threshold detection (VT) in the palate has been recognized in adults with OSA, but has not been studied in children. Both findings are indicative of a defect in the afferent limb of the upper airway dilator reflex that could prevent upper airway dilation secondary to airway loading, resulting in airway collapse. We hypothesized that children with OSA have impaired palate VT compared to controls, and that this improves after OSA treatment. METHODS: Case-control study. Children with OSA and healthy non-snoring controls underwent polysomnography and palate VT measurements. Children with OSA were retested after adenotonsillectomy. RESULTS: 29 children with OSA (median [interquartile range] age = 9.5 [7.5-12.6] years, obstructive apnea-hypopnea index [OAHI] = 11.3 [5.7-19.5] events/h, BMI z = 1.8 [1.3-2.1]) and 32 controls (age = 11.2 [9.3-13.5] years, P = 0.1; OAHI = 0.5 [0.1-0.7] events/h, P < 0.001; BMI z = 1 [0.3-1.7], P = 0.004) were tested. OSA palate VT (1.0 [0.8-1.5] vibration units) was similar to that of controls (1 [0.8-1.3], P = 0.37). 20 children with OSA were retested 4.4 (3.2-7.1) months after treatment. OAHI decreased from 13.1 (5.8-19) to 0.6 (0.2-2.5) events per hour (P < 0.001) postoperatively, but palate VT did not change (before = 1 [0.7-1.5], after = 1.2 [0.8-1.4], P = 0.37). CONCLUSIONS: Children with OSA and controls have similar palate VT. Unlike in adults, palate VT does not seem to be affected by childhood OSA.

Airway Resistance in Children with Obstructive Sleep Apnea Syndrome.

STUDY OBJECTIVES: Enlarged tonsils and adenoids, the main cause of obstructive sleep apnea syndrome (OSAS) in children, results in upper airway (UA) loading. This contributes to the imbalance between structural and neuromotor factors ultimately leading to UA collapse during sleep. However, it is unknown whether this UA loading can cause elevated airway resistance (AR) during wakefulness. We hypothesized that children with OSAS have elevated AR compared to controls and that this improves after OSAS treatment. METHODS: Case control study performed at an academic hospital. Children with OSAS and nonsnoring healthy controls underwent baseline polysomnography and spirometry, and AR measurement by body plethysmography while breathing via an orofacial mask. Children with OSAS repeated the previously mentioned tests after adenotonsillectomy. RESULTS: 31 OSAS participants (mean age ± SD = 9.7 ± 3.0 y, obstructive apnea-hypopnea index (OAHI) median [range] = 14.9 [2-58.7] events/h, body mass index [BMI] z = 1.5 ± 1) and 31 controls (age = 10.5 ± 2.5 y, P = 0.24; OAHI = 0.4 [0-1.4], P < 0.001; BMI z = 0.9 ± 1, P = 0.01) were tested. OSAS AR at baseline was 3.9 [1.5-10.3] cmH2O/L/sec and controls 2.8 [1.4 - 6.2] (P = 0.027). Both groups had similar spirometry results. 20 patients with OSAS were tested 6.4 ± 6.6 mo after adenotonsillectomy. OAHI decreased from 15.2 [2.1-58.7] to 0.5 [0 - 5.1] events/h postoperatively (P < 0.001), and AR decreased from 4.3 [1.5 - 10.3] to 2.8 [1.7 - 4.7] cmH2O/L/sec (P = 0.009). CONCLUSIONS: Children with OSAS have elevated AR that decreases after treatment. This is likely because of upper airway loading secondary to adenotonsillar hypertrophy and may contribute to the increased frequency of respiratory diseases in untreated children with OSAS.

Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome.

STUDY OBJECTIVES: Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. METHODS: CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. RESULTS: Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). CONCLUSIONS: Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS.

Predictors of perioperative complications in higher risk children after adenotonsillectomy for obstructive sleep apnea: a prospective study.

OBJECTIVE: Retrospective studies have limitations in predicting perioperative risk following adenotonsillectomy in children with obstructive sleep apnea syndrome (OSAS). Few prospective studies exist. We hypothesized that demographic and polysomnographic (PSG) variables would predict respiratory and general perioperative complications. STUDY DESIGN: Prospective, observational cohort study. SETTING: Pediatric tertiary center. SUBJECTS AND METHODS: Consecutive children undergoing adenotonsillectomy for OSAS within 12 months of PSG were evaluated for complications occurring within 2 weeks of surgery. RESULTS: There were 329 subjects, with 27% <3 years old, 24% obese, 16% preterm, and 29% with comorbidities. In this higher risk population, 28% had respiratory complications (major and/or minor), and 33% had nonrespiratory complications. Significant associations were found between PSG parameters and respiratory complications as follows: apnea hypopnea index (rank-biserial correlation coefficient [r] = 0.174, P = .017), SpO2 nadir (r = -0.332, P < .0005), sleep time with SpO2 <90% (r = 0.298, P < .0005), peak end-tidal CO2 (r = 0.354, P < .0005), and sleep time with end-tidal CO2 >50 mm Hg (r = 0.199, P = .006). Associations were also found between respiratory complications and age <3 years (r = -0.174, P = .003) or black race (r = 0.123, P = .039). No significant associations existed between PSG parameters and nonrespiratory complications. A model using age <3 years, SpO2 nadir, and peak CO2 predicted respiratory complications better than the American Academy of Pediatrics or American Academy of Otolaryngology-Head and Neck Surgery Foundation guidelines but was imperfect (area under the curve = 0.72). CONCLUSION: Thus, PSG predicted perioperative respiratory, but not nonrespiratory, complications in children with OSAS. Age <3 years or black race are high-risk factors. Present guidelines have limitations in determining the need for postoperative admission.

Pilot study of nasal expiratory positive airway pressure devices for the treatment of childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Alternative therapies for childhood obstructive sleep apnea syndrome (OSAS) are needed as OSAS may persist despite adenotonsillectomy, and continuous positive airway pressure (CPAP) adherence is low. Nasal expiratory positive airway pressure (NEPAP) devices have not been studied in children. We hypothesized that NEPAP would result in polysomnographic improvement. Further, we aimed to determine NEPAP adherence, effects on sleepiness, behavior, and quality of life. METHODS: A randomized, double-blind, placebo-controlled, crossover pilot study was performed. CPAP candidates, 8-16 years old, underwent NEPAP and placebo polysomnograms. Subjects with ≥ 50% reduction in the apnea hypopnea index (AHI) from placebo to NEPAP night or AHI < 5/h on NEPAP night wore NEPAP at home for 30 days. Adherence was assessed by daily phone calls/emails and collecting used devices. RESULTS: Fourteen subjects (age 13.4 ± 1.9 years, BMI z-scores 2.2 ± 1 [mean ± SD]) were studied. There was significant improvement in the obstructive apnea index with NEPAP vs. placebo: 0.6 (0-21.1)/h vs. 4.2 (0-41.9)/h (median [range], p = 0.010) and trends for improvement in other polysomnographic parameters. However, responses were variable, with 3 subjects not improving and 2 worsening. Older children and those with less hypercapnia had a better response. Eight subjects were sent home with devices; one was lost to follow-up, and adherence in the remainder was 83% of nights; these subjects had a significant improvement in sleepiness and quality of life. CONCLUSIONS: NEPAP devices are a potential alternative therapy for OSAS in a small subset of children. Due to variability in individual responses, efficacy of NEPAP should be evaluated with polysomnography. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT01768065.

Predictors of positive airway pressure therapy adherence in children: a prospective study.

STUDY OBJECTIVES: Children with obstructive sleep apnea are increasingly being treated with positive airway pressure (PAP), particularly if they have underlying medical conditions. Although PAP is an effective treatment, its use is challenging due to poor adherence. We hypothesized that demographic, psychosocial, and polysomnographic parameters would be related to PAP adherence. We therefore prospectively collected data potentially pertaining to PAP adherence, and correlated it with PAP use. METHODS: Fifty-six patients and their parents completed a series of psychosocial questionnaires prior to PAP initiation. Objective adherence data were obtained after 1 and 3 months of PAP use. RESULTS: The population was primarily obese; 23% had neurodevelopmental disabilities. PAP adherence varied widely, with PAP being worn 22 ± 8 nights in month-1, but mean use was only 3 ± 3 h/night. The greatest predictor of use was maternal education (p = 0.002 for nights used; p = 0.033 for mean h used/night). Adherence was lower in African American children vs other races (p = 0.021). In the typically developing subgroup, adherence correlated inversely with age. Adherence did not correlate with severity of apnea, pressure levels, or psychosocial parameters other than a correlation between family social support and nights of PAP use in month-3. CONCLUSIONS: PAP adherence in children and adolescents is related primarily to family and demographic factors rather than severity of apnea or measures of psychosocial functioning. Further research is needed to determine the relative contributions of maternal education, socioeconomic status and cultural beliefs to PAP adherence in children, in order to develop better adherence programs.

Randomized, double-blind clinical trial of two different modes of positive airway pressure therapy on adherence and efficacy in children.

STUDY OBJECTIVES: To determine the effects of bilevel positive airway pressure with pressure release technology (Bi-Flex) on adherence and efficacy in children and adolescents compared to standard continuous positive airway pressure (CPAP) therapy. We hypothesized that Bi-Flex would result in improved adherence but similar efficacy to CPAP. METHODS: This was a randomized, double-blinded clinical trial. Patients with obstructive sleep apnea were randomized to CPAP or Bi-Flex. Repeat polysomnography was performed on pressure at 3 months. Objective adherence data were obtained at 1 and 3 months. RESULTS: 56 children and adolescents were evaluated. There were no significant differences in the number of nights the device was turned on, or the mean number of minutes used at pressure per night for CPAP vs Bi-Flex (24 ± 6 vs 22 ± 9 nights, and 201 ± 135 vs 185 ± 165 min, respectively, for Month 1). The apnea hypopnea index decreased significantly from 22 ± 21/h to 2 ± 3/h on CPAP (p = 0.005), and 18 ± 15/h to 2 ± 2/h on Bi-Flex (p < 0.0005), but there was no significant difference between groups (p = 0.82 for CPAP vs Bi-Flex). The Epworth Sleepiness Scale decreased from 8 ± 5 to 6 ± 3 on CPAP (p = 0.14), and 10 ± 6 to 5 ± 5 on Bi-Flex (p < 0.0005; p = 0.12 for CPAP vs Bi-Flex). CONCLUSIONS: Both CPAP and Bi-Flex are efficacious in treating children and adolescents with OSAS. However, adherence is suboptimal with both methods. Further research is required to determine ways to improve adherence in the pediatric population.

Effects of positive airway pressure therapy on neurobehavioral outcomes in children with obstructive sleep apnea.

RATIONALE: Positive airway pressure therapy is frequently used to treat obstructive sleep apnea in children. However, it is not known whether positive airway pressure therapy results in improvements in the neurobehavioral abnormalities associated with childhood sleep apnea. OBJECTIVES: We hypothesized that positive airway pressure therapy would be associated with improvements in attention, sleepiness, behavior, and quality of life, and that changes would be associated with therapy adherence. METHODS: Neurobehavioral assessments were performed at baseline and after 3 months of positive airway pressure therapy in a heterogeneous group of 52 children and adolescents. MEASUREMENTS AND MAIN RESULTS: Adherence varied widely (mean use, 170 ± 145 [SD] minutes per night). Positive airway pressure therapy was associated with significant improvements in attention deficits (P < 0.001); sleepiness on the Epworth Sleepiness Scale (P < 0.001); behavior (P < 0.001); and caregiver- (P = 0.005) and child- (P < 0.001) reported quality of life. There was a significant correlation between the decrease in Epworth Sleepiness Scale at 3 months and adherence (r = 0.411; P = 0.006), but not between other behavioral outcomes and adherence. Behavioral factors also improved in the subset of children with developmental delays. CONCLUSIONS: These results indicate that, despite suboptimal adherence use, there was significant improvement in neurobehavioral function in children after 3 months of positive airway pressure therapy, even in developmentally delayed children. The implications for improved family, social, and school function are substantial. Clinical trial registered with www.clinicaltrials.gov (NCT 00458406).