Study objectives

Depression is prevalent among patients with sleep disorders, and studies show associations between suicidal ideation and insufficient sleep. Using retrospective clinic records, we examined positive depression screening rates among adolescent sleep clinic patients relative to other subspecialty clinic patients. We also examined relationships between sleep diagnoses and positive depression screening rate in adolescent sleep clinic patients.

Methods

Data were analyzed from patients ages 12-18 (n = 12,520) who were screened for depression using the Patient Health Questionnaire-2 (PHQ-2). Those who screened positive were administered the PHQ-9. Logistic regression was used to examine effects of age, sex, race, ethnicity, and clinic on likelihood of a positive depression screen. Within sleep clinic patients (n = 308), demographic factors, sleep disorder diagnosis, and body mass index percentile were examined using logistic and linear regression.

Results

Among all patients screened, older age and female sex predicted positive depression screens. Sleep clinic patients were more likely to screen positive than patients in 9 other clinics [odds ratios 2.03-6.83]. Results were similar even when the PHQ-9 sleep item was excluded [odds ratios 2.18-6.41]. Within sleep clinic patients, sleep disorder diagnosis (eg, insomnia, obstructive sleep apnea) was predictive of a positive depression screen (χ²(1) = 10.88, P = .004): insomnia patients were most likely to be experiencing depression.

Conclusions

Adolescent sleep clinic patients are at increased risk for depressive symptoms. Among insomnia patients, risk was independent of age, sex, and obesity, suggesting a unique relationship between insomnia and affective distress, as has been found in adults. Assessing adolescents for sleep disorders should be prioritized, given the strong association with depression.

Study objectives

The efficacy of portable-monitor (PM) sleep testing in children is not well understood. While most studies have evaluated PM in a lab setting, the utility of PM in the home environment is relatively unknown. We sought to determine whether home PM accurately diagnoses obstructive sleep apnea in adolescents and to assess patient satisfaction with home PM sleep testing.

Methods

We evaluated adolescents (age 12-18 years) with suspected obstructive sleep apnea using a PM device. In addition to in-laboratory polysomnography (PSG), all participants had PM testing performed twice, once in their home and once concurrent to in-laboratory PSG. PM was compared to PSG using 2 primary outcomes: the apnea-hypopnea index and oxygen desaturation index. All participants were approached for interview to evaluate their experience with PM sleep testing.

Results

Twenty adolescents participated. Bland-Altman analysis comparing the apnea-hypopnea index and oxygen desaturation index determined by home or in-laboratory PM to in-laboratory PSG revealed mostly agreement; however, some deviations were observed when either parameter was markedly increased. While PM testing tended to underestimate the apnea-hypopnea index, the diagnostic agreement between home PM and PSG was 80% (by the White-Westbrook method). Most preferred PM to PSG and found PM easy to very easy to set up.

Conclusions

In a small cohort of adolescents, our study supports the application of home PM in the diagnosis of suspected obstructive sleep apnea. Until studies implementing PM using larger cohorts become readily available, the findings from this preliminary study could contribute to adolescents receiving sleep apnea therapy more promptly.

Clinical trial registration

Registry: ClinicalTrials.gov; Identifier: NCT03748771. At the time of issue publication, this registration is not publicly available because the trial includes a device that is not approved or cleared for use in pediatric populations. Once the device is FDA cleared, the registration will become public.

Background

Childhood asthma and obstructive sleep apnea (OSA), both disorders of airway inflammation, were associated in recent observational studies. Although childhood OSA is effectively treated by adenotonsillectomy (AT), it remains unclear whether AT also improves childhood asthma. We hypothesized that AT, the first line of therapy for childhood OSA, would be associated with improved asthma outcomes and would reduce the usage of asthma therapies in children.

Methods and findings

Using the 2003-2010 MarketScan database, we identified 13,506 children with asthma in the United States who underwent AT. Asthma outcomes during 1 y preceding AT were compared to those during 1 y following AT. In addition, 27,012 age-, sex-, and geographically matched children with asthma without AT were included to examine asthma outcomes among children without known adenotonsillar tissue morbidity. Primary outcomes included the occurrence of a diagnostic code for acute asthma exacerbation (AAE) or acute status asthmaticus (ASA). Secondary outcomes included temporal changes in asthma medication prescriptions, the frequency of asthma-related emergency room visits (ARERs), and asthma-related hospitalizations (ARHs). Comparing the year following AT to the year prior, AT was associated with significant reductions in AAE (30.2%; 95% CI: 25.6%-34.3%; p<0.0001), ASA (37.9%; 95% CI: 29.2%-45.6%; p<0.0001), ARERs (25.6%; 95% CI: 16.9%-33.3%; p<0.0001), and ARHs (35.8%; 95% CI: 19.6%-48.7%; p = 0.02). Moreover, AT was associated with significant reductions in most asthma prescription refills, including bronchodilators (16.7%; 95% CI: 16.1%-17.3%; p<0.001), inhaled corticosteroids (21.5%; 95% CI: 20.7%-22.3%; p<0.001), leukotriene receptor antagonists (13.4%; 95% CI: 12.9%-14.0%; p<0.001), and systemic corticosteroids (23.7%; 95% CI: 20.9%-26.5%; p<0.001). In contrast, there were no significant reductions in these outcomes in children with asthma who did not undergo AT over an overlapping follow-up period. Limitations of the MarketScan database include lack of information on race and obesity status. Also, the MarketScan database does not include information on children with public health insurance (i.e., Medicaid) or uninsured children.

Conclusions

In a very large sample of privately insured children, AT was associated with significant improvements in several asthma outcomes. Contingent on validation through prospectively designed clinical trials, this study supports the premise that detection and treatment of adenotonsillar tissue morbidity may serve as an important strategy for improving asthma control. Please see later in the article for the Editors' Summary.

BACKGROUND AND OBJECTIVE: Patients with neuromuscular disease are often treated with home noninvasive ventilation (NIV) with devices capable of remote patient monitoring. We sought to determine whether long-term NIV data could provide insight into the effectiveness of ventilation over time. METHODS: We abstracted available longitudinal data for adults with neuromuscular disease in monthly increments from first available to most recent. Generalised linear mixed-effects modelling with subject-level random effects was used to evaluate trajectories over time. RESULTS: 1799 months of data across 85 individuals (median age 61, interquartile range (IQR) 46-71 years; 44% female; 49% amyotrophic lateral sclerosis (ALS)) were analysed, with a median (IQR) of 17 (8-35) months per individual. Over time, tidal volume increased and respiratory rate decreased. Dynamic respiratory system compliance decreased, accompanied by increased pressure support. Compared to volume-assured mode, fixed-pressure modes were associated with lower initial tidal volume, higher respiratory rate and lower pressures, which did not fully equalise with volume-assured mode over time. Compared with non-ALS patients, those with ALS had lower initial pressure support, but faster increases in pressure support over time, and ALS was associated wtih a more robust increase in respiratory rate in response to low tidal volume. Nonsurvivors did not differ from survivors in ventilatory trajectories over time, but did exhibit decreasing NIV use prior to death, in contrast with stable use in survivors. CONCLUSION: NIV keeps breathing patterns stable over time, but support needs are dynamic and influenced by diagnosis and ventilation mode. Mortality is preceded by decreased NIV use rather than inadequate support during use.

Study objectives

Few studies have examined the validity of actigraphy in school-aged children. The objective of this study was to examine the validity of a commonly used actigraph compared to polysomnography (PSG) in a sample of children age 5 to 12 y born prematurely, sleeping in their natural home environment.

Methods

148 children born preterm (85 boys and 63 girls), ages 5-12 y (mean = 9.3 y, standard deviation = 2.0) wore the Philips Respironics Actiwatch-2 for 1 night concurrently with comprehensive, ambulatory PSG in the child's home. Sleep outcome variables were sleep onset latency, total sleep time (TST), and sleep efficiency. Epoch-by-epoch comparisons were used to determine sensitivity, specificity, and accuracy. Secondary analyses examined differences between children with no sleep issues, obstructive sleep apnea syndrome, and periodic limb movements in sleep (PLMS).

Results

Actigraphy significantly underestimated TST (30 min) and sleep efficiency (5%). Actigraphy underestimated or overestimated sleep onset latency by at least 10 min for a third of the children. Sensitivity and accuracy were good at 0.88 and 0.84, respectively, whereas specificity was lower at 0.46. Differences between actigraphy and PSG for TST and sleep efficiency were greatest for children with PLMS.

Conclusions

This study adds to the small existing literature demonstrating the validity of actigraphy in middle childhood. Although actigraphy shows good sensitivity (ability to detect sleep), specificity (ability to detect wake) is poor in this age group. Further, the results highlight the importance of considering whether a child has PLMS when interpreting actigraphic data, as well as the difficulties in accurately capturing sleep onset latency with actigraphy.

Background

Obstructive sleep apnea (OSA) is associated with adverse and interdependent cognitive and cardiovascular consequences. Increasing evidence suggests that nitric oxide synthase (NOS) and endothelin family (EDN) genes underlie mechanistic aspects of OSA-associated morbidities. We aimed to identify single nucleotide polymorphisms (SNPs) in the NOS family (3 isoforms), and EDN family (3 isoforms) to identify potential associations of these SNPs in children with OSA.

Methods

A pediatric community cohort (ages 5-10 years) enriched for snoring underwent overnight polysomnographic (NPSG) and a fasting morning blood draw. The diagnostic criteria for OSA were an obstructive apnea-hypopnea Index (AHI) >2/h total sleep time (TST), snoring during the night, and a nadir oxyhemoglobin saturation <92%. Control children were defined as non-snoring children with AHI <2/h TST (NOSA). Endothelial function was assessed using a modified post-occlusive hyperemic test. The time to peak reperfusion (Tmax) was considered as the indicator for normal endothelial function (NEF; Tmax<45 sec), or ED (Tmax ≥ 45 sec). Genomic DNA from peripheral blood was extracted and allelic frequencies were assessed for, NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), endothelin receptor A, EDNRA, (27 SNPs), and endothelin receptor B, EDNRB (23 SNPs) using a custom SNPs array. The relative frequencies of NOS-1,-2, and -3, and EDN-1,-2,-3,-EDNRA, and-EDNRB genotypes were evaluated in 608 subjects [128 with OSA, and 480 without OSA (NOSA)]. Furthermore, subjects with OSA were divided into 2 subgroups: OSA with normal endothelial function (OSA-NEF), and OSA with endothelial dysfunction (OSA-ED). Linkage disequilibrium was analyzed using Haploview version 4.2 software.

Results

For NOSA vs. OSA groups, 15 differentially distributed SNPs for NOS1 gene, and 1 SNP for NOS3 emerged, while 4 SNPs for EDN1 and 1 SNP for both EDN2 and EDN3 were identified. However, in the smaller sub-group for whom endothelial function was available, none of the significant SNPs was retained due to lack of statistical power.

Conclusions

Differences in the distribution of polymorphisms among NOS and EDN gene families suggest that these SNPs could play a contributory role in the pathophysiology and risk of OSA-induced cardiovascular morbidity. Thus, analysis of genotype-phenotype interactions in children with OSA may assist in the formulation of categorical risk estimates.

Objectives

Obesity is a risk factor for obstructive sleep apnea (OSA) in children. Childhood obesity rates vary amongst different ethnic groups. Here the interaction of Hispanic ethnicity and obesity on OSA risk was evaluated.

Methods

Retrospective cross-sectional analysis of consecutive children undergoing polysomnography and anthropometry using bioelectrical impedance from 2017 to 2020. Demographics obtained from the medical chart. Children who had also undergone cardiometabolic testing were identified and the relationship of cardiometabolic markers with OSA and anthropometry was assessed.

Results

Data from 1217 children revealed Hispanic children were more likely to have moderate-severe OSA (36.0%) compared to Non-Hispanic children (26.5%), p < 0.001. Hispanic children had greater Body mass index (BMI), BMI percentile and percent body fat, p < 0.0001. In children that underwent cardiometabolic testing, Hispanic children had significantly greater serum alanine aminotransferase levels (ALT) levels. Following adjustment of age and sex, Hispanic ethnicity was not found to moderate the association of anthropometry with OSA, anthropometry with cardiometabolic markers, and OSA with cardiometabolic markers.

Conclusions

OSA was more likely in Hispanic children; this relationship was likely driven by obesity status rather than ethnicity. Among children undergoing cardiometabolic testing, Hispanic children were observed to have greater ALT concentrations however ethnicity did not impact the association of anthropometry and ALT or other cardiometabolic markers.

Study objectives

Longitudinal studies support the usage of positive airway pressure (PAP) therapy in treating obstructive sleep apnea (OSA) to improve cardiovascular disease. However, the anticipated benefit is not ubiquitous. In this study, we elucidate whether PAP therapy leads to immediate improvements on endothelial function, a subclinical marker of cardiovascular status, by examining the effect of circulating exosomes, isolated from patients before and after PAP therapy, on naive endothelial cells.

Methods

We isolated plasma-derived circulating exosomes from 12 patients with severe OSA and obesity hypoventilation syndrome (OHS) before and after 6 weeks of PAP therapy, and examined their effect on cultured endothelial cells using several in vitro reporter assays.

Results

We found that circulating exosomes contributed to the induction and propagation of OSA/OHS-related endothelial dysfunction (ie, increased permeability and disruption of tight junctions along with increased adhesion molecule expression, and reduced endothelial nitric oxide synthase expression), and promoted increased monocyte adherence. Further, when comparing exosomes isolated before and after PAP therapy, the disturbances in endothelial cell function were attenuated with treatment, including an overall cumulative decrease in endothelial permeability in all 12 subjects by 10.8% (P = .035), as well as detection of a subset of 4 differentially expressed exosomal miRNAs, even in the absence of parallel changes in systemic blood pressure or metabolic function.

Conclusions

Circulating exosomes facilitate important intercellular signals that modify endothelial phenotype, and thus emerge as potential fundamental contributors in the context of OSA/OHS-related endothelial dysfunction. Exosomes may not only provide candidate biomarkers, but are also a likely and plausible mechanism toward OSA/OHS-induced cardiovascular disease.

Clinical trial registration

Registry: ClinicalTrials.gov, Title: AVAPS-AE Efficacy Study, URL: https://clinicaltrials.gov/ct2/show/NCT01368614, Identifier: NCT01368614.

Background

The presence of endothelial dysfunction (ED) constitutes an early risk factor for cardiovascular disease (CVD) in children. Nitric oxide (NO) and endothelin (EDN) are generated in endothelial cells and are critical regulators of vascular function, with ED resulting from an imbalance between these two molecules. We hypothesized that genetic variants in NO synthase and EDN isoforms and its receptors (EDNRA and EDNRB) may account for a proportion of the risk for ED in developing children.

Methods

Consecutive children (ages 5-10 years) were prospectively recruited from the community. Time to peak post-occlusive reperfusion (Tmax) was considered as the indicator of either normal endothelial function (NEF; Tmax < 45 sec) or ED (Tmax ≥ 45 sec). Lipid profiles, high sensitivity C-reactive protein (hsCRP), fasting glucose and insulin were assayed using ELISA. Genomic DNA from peripheral blood was extracted and genotyped for NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), EDNRA (27 SNPs), and EDNRB (23 SNPs) using a custom SNPs array. Linkage disequilibrium was analyzed using Haploview version 4.2 software.

Results

The relative frequencies of SNPs were evaluated in 122 children, 84 with NEF and 38 with ED. The frequencies of NOS1 (11 SNPs), and EDN1 (2 SNPs) were differentially distributed between NEF vs. ED, and no significant differences emerged for all other genes. Significant SNPs for NOS1 and EDN1 SNPs were further validated with RT-PCR.

Conclusions

Genetic variants in the NOS1 and EDN1 genes appear to account for important components of the variance in endothelial function, particularly when concurrent risk factors such as obesity exist. Thus, analysis of genotype-phenotype interactions in children at risk for ED will be critical for more accurate formulation of categorical CVD risk estimates.

There is a need for alternatives to positive airway pressure for the treatment of obstructive sleep apnea and snoring. Improving upper airway dilator function might alleviate upper airway obstruction. We hypothesized that transoral neuromuscular stimulation would reduce upper airway collapse in concert with improvement in genioglossal muscle function. Subjects with simple snoring and mild OSA (AHI < 15/h on screening) underwent in-laboratory polysomnography with concurrent genioglossal electromyography (EMGgg) before and after 4-6 weeks of twice-daily transoral neuromuscular stimulation. Twenty patients completed the study: Sixteen males, mean ± SD age 40 ± 13 years, and BMI 26.3 ± 3.8 kg/m² . Although there was no change in non-rapid eye movement EMGgg phasic (p = 0.66) or tonic activity (p = 0.83), and no decrease in snoring or flow limitation, treatment was associated with improvements in tongue endurance, sleep quality, and sleep efficiency. In this protocol, transoral neurostimulation did not result in changes in genioglossal activity or upper airway collapse, but other beneficial effects were noted suggesting a need for additional mechanistic investigation.