Adenotonsillectomy for Snoring and Mild Sleep Apnea in Children: A Randomized Clinical Trial.

Importance: The utility of adenotonsillectomy in children who have habitual snoring without frequent obstructive breathing events (mild sleep-disordered breathing [SDB]) is unknown. Objectives: To evaluate early adenotonsillectomy compared with watchful waiting and supportive care (watchful waiting) on neurodevelopmental, behavioral, health, and polysomnographic outcomes in children with mild SDB. Design, Setting, and Participants: Randomized clinical trial enrolling 459 children aged 3 to 12.9 years with snoring and an obstructive apnea-hypopnea index (AHI) less than 3 enrolled at 7 US academic sleep centers from June 29, 2016, to February 1, 2021, and followed up for 12 months. Intervention: Participants were randomized 1:1 to either early adenotonsillectomy (n = 231) or watchful waiting (n = 228). Main Outcomes and Measures: The 2 primary outcomes were changes from baseline to 12 months for caregiver-reported Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite (GEC) T score, a measure of executive function; and a computerized test of attention, the Go/No-go (GNG) test d-prime signal detection score, reflecting the probability of response to target vs nontarget stimuli. Twenty-two secondary outcomes included 12-month changes in neurodevelopmental, behavioral, quality of life, sleep, and health outcomes. Results: Of the 458 participants in the analyzed sample (231 adenotonsillectomy and 237 watchful waiting; mean age, 6.1 years; 230 female [50%]; 123 Black/African American [26.9%]; 75 Hispanic [16.3%]; median AHI, 0.5 [IQR, 0.2-1.1]), 394 children (86%) completed 12-month follow-up visits. There were no statistically significant differences in change from baseline between the 2 groups in executive function (BRIEF GEC T-scores: -3.1 for adenotonsillectomy vs -1.9 for watchful waiting; difference, -0.96 [95% CI, -2.66 to 0.74]) or attention (GNG d-prime scores: 0.2 for adenotonsillectomy vs 0.1 for watchful waiting; difference, 0.05 [95% CI, -0.18 to 0.27]) at 12 months. Behavioral problems, sleepiness, symptoms, and quality of life each improved more with adenotonsillectomy than with watchful waiting. Adenotonsillectomy was associated with a greater 12-month decline in systolic and diastolic blood pressure percentile levels (difference in changes, -9.02 [97% CI, -15.49 to -2.54] and -6.52 [97% CI, -11.59 to -1.45], respectively) and less progression of the AHI to greater than 3 events/h (1.3% of children in the adenotonsillectomy group compared with 13.2% in the watchful waiting group; difference, -11.2% [97% CI, -17.5% to -4.9%]). Six children (2.7%) experienced a serious adverse event associated with adenotonsillectomy. Conclusions: In children with mild SDB, adenotonsillectomy, compared with watchful waiting, did not significantly improve executive function or attention at 12 months. However, children with adenotonsillectomy had improved secondary outcomes, including behavior, symptoms, and quality of life and decreased blood pressure, at 12-month follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT02562040.

Nocturnal peripheral vasoconstriction predicts the frequency of severe acute pain episodes in children with sickle cell disease.

The basic model of SCD physiology states that vaso-occlusion occurs when hemoglobin S-containing red blood cells (RBC) undergo sickling before they escape the capillary into a larger vessel. We have shown that mental stress, pain and cold, and events reported by patients to trigger SCD vaso-occlusive crisis (VOC), cause rapid and significant decrease in blood flow, reducing the likelihood that RBC could transit the microvasculature before sickling occurs. However, the critical link between decrease in microvascular blood flow and the incidence of future sickle VOC has never been established experimentally in humans. Using data from centrally adjudicated, overnight polysomnograms (PSG), previously collected in a prospective multi-center cohort sleep study, we analyzed the beat-to-beat amplitudes of vasoconstriction reported by the fingertip photoplethysmogram in 212 children and adolescents with SCD and developed an algorithm that detects vasoconstriction events and quantifies the magnitude (Mvasoc ), duration, and frequency of vasoconstriction that reflect the individual's inherent peripheral vasoreactivity. The propensity to vasoconstrict, quantified by median Mvasoc , predicted the incidence rate of post-PSG severe acute vaso-occlusive pain events (P = .006) after accounting for age and hemoglobin. Indices of sleep-disordered breathing contributed to median Mvasoc but did not predict future pain rate. Median Mvasoc was not associated with vaso-occlusive pain events that occurred prior to each PSG. These results show that SCD individuals with high inherent propensity to vasoconstrict have more frequent severe acute pain events. Our empirical findings are consistent with the fundamental SCD hypothesis that decreased microvascular flow promotes microvascular occlusion.

Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia.

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18 years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P < 0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P = 0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA.

Sleep disordered breathing does not predict acute severe pain episodes in children with sickle cell anemia.

Conflicting evidence has suggested that low mean nocturnal hemoglobin oxygen saturation (SpO2 ) predicts future hospital days for acute severe pain in children with sickle cell anemia (SCA). In an unselected multicenter prospective cohort study, we tested the hypothesis that either low mean nocturnal SpO2 or high obstructive apnea-hypopnea index (OAHI; the number of obstructive apneas and hypopneas with ≥ 3% desaturation or arousal per hour of sleep) or high oxygen desaturation index (ODI; number of ≥ 3% desaturation from baseline saturation per hour of sleep) is associated with increased incidence rates of pain. A total of 140 children with SCA with a median age of 10.8 years (interquartile range 7.2) were followed for a median of 4.9 years (interquartile range 1.8). Overnight polysomnography evaluations at baseline health exam were measured and adjudicated centrally. Multivariable models created in two steps were included. First, all plausible covariates were included in a screening model. Subsequently, covariates meeting level of statistical significance of P < .20 were included in the final model. Contrary to our hypothesis, higher (but not lower) mean nocturnal SpO2 was associated with higher rates of pain episodes (Incidence rate ratio (IRR) 1.10, 95% CI [1.03-1.18], P = .004). Higher log OAHI did not pass screening criteria. Higher log ODI was not significantly associated with higher rates of pain episodes (IRR 0.93, 95% CI [0.82-1.06], P = .28). Neither low nocturnal SpO2, higher OAHI, nor higher ODI were associated with clinically relevant increased incidence rates of acute severe pain episodes.

Exhaled nitric oxide: Not associated with asthma, symptoms, or spirometry in children with sickle cell anemia.

BACKGROUND: The significance of fractional exhaled nitric oxide (Feno) levels in children with sickle cell anemia (SCA) is unclear, but increased levels can be associated with features of asthma and thus increased morbidity. OBJECTIVES: We sought to determine factors associated with Feno and whether Feno levels are associated with increased rates of acute chest syndrome (ACS) and pain. METHODS: All participants had SCA, were part of the prospective observational Sleep and Asthma Cohort study, and had the following assessments: Feno levels, spirometry, blood samples analyzed for hemoglobin, white blood cell counts, eosinophil counts and total serum IgE levels, questionnaires about child medical and family history, and review of medical records. RESULTS: The analytic sample included 131 children with SCA (median age, 11.2 years; age range, 6-18 years) followed for a mean of 16.2 years, including a mean of 5.1 years after baseline Feno data measurements. In multivariable analyses higher Feno levels were associated with ln(IgE) levels (P < .001) and the highest quartile of peripheral eosinophil counts (P = .03) but not wheezing symptoms, baseline spirometric indices, or response to bronchodilator. Multivariable analyses identified that the incident rate of ACS was associated with ln(Feno) levels (P = .03), as well as male sex (P = .025), wheezing causing shortness of breath (P = .002), and ACS at less than 4 years of age (P < .001). Feno levels were not associated with future pain episodes. CONCLUSIONS: Steady-state Feno levels were not associated with an asthma diagnosis, wheezing symptoms, lung function measures, or prior sickle cell morbidity but were associated with markers of atopy and increased risk of future ACS events.

A randomized trial of adenotonsillectomy for childhood sleep apnea.

BACKGROUND: Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome, yet its usefulness in reducing symptoms and improving cognition, behavior, quality of life, and polysomnographic findings has not been rigorously evaluated. We hypothesized that, in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation, early adenotonsillectomy, as compared with watchful waiting with supportive care, would result in improved outcomes. METHODS: We randomly assigned 464 children, 5 to 9 years of age, with the obstructive sleep apnea syndrome to early adenotonsillectomy or a strategy of watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were assessed at baseline and at 7 months. RESULTS: The average baseline value for the primary outcome, the attention and executive-function score on the Developmental Neuropsychological Assessment (with scores ranging from 50 to 150 and higher scores indicating better functioning), was close to the population mean of 100, and the change from baseline to follow-up did not differ significantly according to study group (mean [±SD] improvement, 7.1±13.9 in the early-adenotonsillectomy group and 5.1±13.4 in the watchful-waiting group; P=0.16). In contrast, there were significantly greater improvements in behavioral, quality-of-life, and polysomnographic findings and significantly greater reduction in symptoms in the early-adenotonsillectomy group than in the watchful-waiting group. Normalization of polysomnographic findings was observed in a larger proportion of children in the early-adenotonsillectomy group than in the watchful-waiting group (79% vs. 46%). CONCLUSIONS: As compared with a strategy of watchful waiting, surgical treatment for the obstructive sleep apnea syndrome in school-age children did not significantly improve attention or executive function as measured by neuropsychological testing but did reduce symptoms and improve secondary outcomes of behavior, quality of life, and polysomnographic findings, thus providing evidence of beneficial effects of early adenotonsillectomy. (Funded by the National Institutes of Health; CHAT ClinicalTrials.gov number, NCT00560859.).

Increased risk of severe vaso-occlusive episodes after initial acute chest syndrome in children with sickle cell anemia less than 4 years old: Sleep and asthma cohort.

Previous studies have shown that the highest incidence of acute chest syndrome (ACS) in sickle cell disease occurs in children <4 years old, and a history of ACS at this age is a risk factor for future ACS episodes. However, the interval associated with the highest risk of subsequent ACS or severe pain is not known. Through this mixed retrospective-prospective observational study, the Sleep and Asthma Cohort, we sought to determine the interval after an initial ACS episode during which the majority of children <4 years old are rehospitalized for ACS or severe pain. The cumulative prevalence of rehospitalization for ACS or severe pain within 6 months, 1 years, and 2 years was calculated for children with an initial ACS episode <4 years old and compared to children with an initial ACS episode ≥4 years old. A total of 44.8% and 55.2% of participants had an initial ACS episode <4 years and ≥4 years old (Range: 4-17.7 years), respectively. At 1 year following the initial ACS episode, children <4 years old had a significantly higher cumulative prevalence of rehospitalizations for ACS or pain as compared to children ≥4 years of age, 62.5 and 39.1%, respectively (P = 0.009). After initial ACS episodes, the majority of children <4 years old will be rehospitalized for ACS or severe pain within one year, suggesting the need for a therapeutic intervention for this high-risk group.

Wheezing symptoms and parental asthma are associated with a physician diagnosis of asthma in children with sickle cell anemia.

OBJECTIVE: To identify factors associated with asthma associated with increased sickle cell anemia (SCA). STUDY DESIGN: Children with SCA (N = 187; mean age 9.6 years, 48% male) were classified as having "asthma" based on parent report of physician diagnosis plus prescription of asthma medication (n = 53) or "no asthma" based on the absence of these features (n = 134). Pain and acute chest syndrome (ACS) events were collected prospectively. RESULTS: Multiple variable logistic regression model identified 3 factors associated with asthma: parent with asthma (P = .006), wheezing causing shortness of breath (P = .001), and wheezing after exercise (P < .001). When ≥2 features were present, model sensitivity was 100%. When none of the features were present, model sensitivity was 0%. When only 1 feature was present, model sensitivity was also 0%, and presence of ≥2 of positive allergy skin tests, airway obstruction on spirometry, and bronchodilator responsiveness did not improve clinical utility. ACS incident rates were significantly higher in individuals with asthma than in those without asthma (incident rate ratio 2.21, CI 1.31-3.76), but pain rates were not (incident rate ratio 1.28, CI 0.78-2.10). CONCLUSIONS: For children with SCA, having a parent with asthma and specific wheezing symptoms are the best features to distinguish those with and without parent report of a physician diagnosis of asthma and to identify those at higher risk for ACS events. The value of treatment for asthma in the prevention of SCA morbidity needs to be studied.

Factors predicting future ACS episodes in children with sickle cell anemia.

While a doctor-diagnosis of asthma is associated with an increased risk of pain and acute chest syndrome (ACS) in children with sickle cell anemia (SCA), little is known about the relationship between specific asthma characteristics and clinical factors and future morbidity in children with SCA. We evaluated the relationship between (i) asthma risk factors at the time of a clinical visit (respiratory symptoms, maternal history of asthma, allergy skin tests, spirometry results) and (ii) the known risk factor of ACS early in life, on prospective pain and ACS episodes in a cohort of 159 children with SCA followed from birth to a median of 14.7 years. An ACS episode prior to 4 years of age, (incidence rate ratio [IRR] = 2.84; P < 0.001], female gender (IRR = 1.80; P = 0.009), and wheezing causing shortness of breath (IRR = 1.68; P = 0.042) were associated with future ACS rates. We subsequently added spirometry results (obstruction defined as FEV1 /FVC less than the lower limits of normal; and bronchodilator response, FEV1 ≥ 12%) and prick skin test responses to the model. Only ≥ 2 positive skin tests had a significant effect (IRR 1.87; P = 0.01). Thus, early in life ACS events, wheezing causing shortness of breath, and ≥ 2 positive skin tests predict future ACS events.

Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in children: guidance from the American Academy of Sleep Medicine.

The American Academy of Sleep Medicine commissioned a task force of clinical experts in pediatric sleep medicine to review published literature on performing the Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test for diagnosis and management of central disorders of hypersomnolence among children and adolescents. This paper follows a format similar to that of the paper "Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine" that was published in 2021. Since there is insufficient evidence to specify a recommended protocol for the Maintenance of Wakefulness Test in children and adolescents, this paper focuses only on the MSLT protocol. This protocol paper provides guidance to health care providers who order, sleep specialists who interpret, and technical staff who administer the MSLT to pediatric patients. Similar to the adult protocol paper, this document provides guidance based on pediatric expert consensus and evidence-based data when available. Topics include patient preparation, evaluation of medication and substance use, sleep needs before testing, scheduling considerations, optimal test conditions for youth, and documentation. Specific changes recommended for pediatric MSLT protocols include (1) provision of a minimum of 7 hours of sleep (with a minimum 8-hour recording time) on polysomnography the night before the MSLT, ideally meeting age-based needs; (2) use of clinical judgment to guide the need for sleep-disordered breathing treatments before polysomnography-MSLT testing; and (3) shared patient-health care provider decision-making regarding modifications in the protocol for children and adolescents with neurodevelopmental/neurological disorders, young age, and/or delayed sleep phase. CITATION: Maski KP, Amos LB, Carter JC, Koch EE, Kazmi U, Rosen CL. Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in children: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med. 2024;20(4):631-641.

Neighborhood Disadvantage, Quality of Life, and Symptom Burden in Children with Mild Sleep-disordered Breathing.

Rationale: Neighborhood disadvantage (ND) has been associated with sleep-disordered breathing (SDB) in children. However, the association between ND and SDB symptom burden and quality of life (QOL) has not yet been studied.Objectives: To evaluate associations between ND with SDB symptom burden and QOL.Methods: Cross-sectional analyses were performed on 453 children, ages 3-12.9 years, with mild SDB (habitual snoring and apnea-hypopnea index < 3/h) enrolled in the PATS (Pediatric Adenotonsillectomy Trial for Snoring) multicenter study. The primary exposure, neighborhood disadvantage, was characterized by the Child Opportunity Index (COI) (range, 0-100), in which lower values (specifically COI ⩽ 40) signify less advantageous neighborhoods. The primary outcomes were QOL assessed by the obstructive sleep apnea (OSA)-18 questionnaire (range, 18-126) and SDB symptom burden assessed by the Pediatric Sleep Questionnaire-Sleep-related Breathing Disorder (PSQ-SRBD) scale (range, 0-1). The primary model was adjusted for age, sex, race, ethnicity, maternal education, recruitment site, and season. In addition, we explored the role of body mass index (BMI) percentile, environmental tobacco smoke (ETS), and asthma in these associations.Results: The sample included 453 children (16% Hispanic, 26% Black or African American, 52% White, and 6% other). COI mean (standard deviation [SD]) was 50.3 (29.4), and 37% (n = 169) of participants lived in disadvantaged neighborhoods. Poor SDB-related QOL (OSA-18 ⩾ 60) and high symptom burden (PSQ-SRBD ⩾ 0.33) were found in 30% (n = 134) and 75% (n = 341) of participants, respectively. In adjusted models, a COI increase by 1 SD (i.e., more advantageous neighborhood) was associated with an improvement in OSA-18 score by 2.5 points (95% confidence interval [CI], -4.34 to -0.62) and in PSQ-SRBD score by 0.03 points (95% CI, -0.05 to -0.01). These associations remained significant after adjusting for BMI percentile, ETS, or asthma; however, associations between COI and SDB-related QOL attenuated by 23% and 10% after adjusting for ETS or asthma, respectively.Conclusions: Neighborhood disadvantage was associated with poorer SDB-related QOL and greater SDB symptoms. Associations were partially attenuated after considering the effects of ETS or asthma. The findings support efforts to reduce ETS and neighborhood-level asthma-related risk factors and identify other neighborhood-level factors that contribute to SDB symptom burden as strategies to address sleep-health disparities.Clinical trial registered with www.clinicaltrials.gov (NCT02562040).

Markers for severity of illness associated with decreased snoring in toddlers born ELGA.

AIM: To describe the prevalence of paediatric sleep disordered breathing (SDB) symptoms in extremely low gestational age infants and identify neonatal risk factors, including early exposure to hypoxia and hyperoxia. METHODS: Patients <28 weeks gestation were monitored with high-resolution pulse oximetry. Hypoxia/hyperoxia variables were defined as percentage time of first 4 weeks of life that SaO(2) < 80% or SaO(2) > 98%, respectively. Parents completed part of the OSA-18 questionnaire for symptoms of SDB at 18-22 months. Logistic regression was used to test the association between risk factors and sleep symptoms. RESULTS: Of 182 patients recruited, 138 (76%) completed the questionnaire. The mean gestation was 26 weeks, and mean birth weight 887 grams. Loud snoring (21%) and restless sleep (24%) were the most prevalent symptoms. Female sex was associated with an increased risk of loud snoring (OR, 2.7; CI, 1.13-6.5). Prolonged mechanical ventilation, necrotizing enterocolitis and prolonged caffeine use, however, were inversely correlated with loud snoring. Neither neonatal hypoxia nor hyperoxia were associated with sleep symptoms. CONCLUSIONS: While the prevalence of sleep disordered breathing symptoms is similar to reported rates, we found a sex difference not previously reported. Interestingly, markers for severity of illness show a pattern of being protective against loud snoring.

Associations of actigraphy measures of sleep duration and continuity with executive function, vigilance, and fine motor control in children with snoring and mild sleep-disordered breathing.

STUDY OBJECTIVES: Children with snoring and mild sleep-disordered breathing may be at increased risk for neurocognitive deficits despite few obstructive events. We hypothesized that actigraphy-based sleep duration and continuity associate with neurobehavioral functioning and explored whether these associations vary by demographic and socioeconomic factors. METHODS: 298 children enrolled in the Pediatric Adenotonsillectomy Trial, ages 3 to 12.9 years, 47.3% from racial or ethnic minority groups, with habitual snoring and an apnea-hypopnea index < 3 were studied with actigraphy (mean 7.5 ± 1.4 days) and completed a computerized vigilance task (Go-No-Go) and a test of fine motor control (9-Hole Pegboard). Caregivers completed the Behavior Rating Inventory of Executive Function. Regression analyses evaluated associations between sleep exposures (24-hour and nocturnal sleep duration, sleep fragmentation index, sleep efficiency) with the Behavior Rating Inventory of Executive Function Global Executive Composite index, pegboard completion time (fine motor control), and vigilance (d prime on the Go-No-Go), adjusting for demographic factors and study design measures. RESULTS: Longer sleep duration, higher sleep efficiency, and lower sleep fragmentation were associated with better executive function; each additional hour of sleep over 24 hours associated with more than a 3-point improvement in executive function (P = .002). Longer nocturnal sleep (P = .02) and less sleep fragmentation (P = .001) were associated with better fine motor control. Stronger associations were observed for boys and children less than 6 years old. CONCLUSIONS: Sleep quantity and continuity are associated with neurocognitive functioning in children with mild sleep-disordered breathing, supporting efforts to target these sleep health parameters as part of interventions for reducing neurobehavioral morbidity. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Pediatric Adenotonsillectomy for Snoring (PATS); URL: https://clinicaltrials.gov/ct2/show/NCT02562040; Identifier: NCT02562040. CITATION: Robinson KA, Wei Z, Radcliffe J, et al. Associations of actigraphy measures of sleep duration and continuity with executive function, vigilance, and fine motor control in children with snoring and mild sleep-disordered breathing. J Clin Sleep Med. 2023;19(9):1595-1603.

Enuresis associated with sleep disordered breathing in children with sickle cell anemia.

PURPOSE: Enuresis and sleep disordered breathing are common among children with sickle cell anemia. We evaluated whether enuresis is associated with sleep disordered breathing in children with sickle cell anemia. MATERIALS AND METHODS: Baseline data were used from a multicenter prospective cohort study of 221 unselected children with sickle cell anemia. A questionnaire was used to evaluate, by parental report during the previous month, the presence of enuresis and its severity. Overnight polysomnography was used to determine the presence of sleep disordered breathing by the number of obstructive apneas and/or hypopneas per hour of sleep. Logistic and ordinal regression models were used to evaluate the association of sleep disordered breathing and enuresis. RESULTS: The mean age of participants was 10.1 years (median 10.0, range 4 to 19). Enuresis occurred in 38.9% of participants and was significantly associated with an obstructive apnea-hypopnea index of 2 or more per hour after adjusting for age and gender (OR 2.19; 95% CI 1.09, 4.40; p = 0.03). Enuresis severity was associated with obstructive apneas and hypopneas with 3% or more desaturation 2 or more times per hour with and without habitual snoring (OR 3.23; 95% CI 1.53, 6.81; p = 0.001 and OR 2.07; 95% CI 1.09, 3.92; p = 0.03, respectively). CONCLUSIONS: In this unselected group of children with sickle cell anemia, sleep disordered breathing was associated with enuresis. Results of this study support that children with sickle cell anemia who present with enuresis should be evaluated by a pulmonologist for sleep disordered breathing.

Sleep-disordered breathing is associated with asthma severity in children.

OBJECTIVE: To examine the relationships among obesity, sleep-disordered breathing (SDB, defined as intermittent nocturnal hypoxia and habitual snoring), and asthma severity in children. We hypothesized that obesity and SDB are associated with severe asthma at a 1- year follow-up. STUDY DESIGN: Children aged 4-18 years were recruited sequentially from a specialty asthma clinic and underwent physiological, anthropometric, and biochemical assessment at enrollment. Asthma severity was determined after 1 year of follow-up and guideline-based treatment, using a composite measure of level of controller medication, symptom burden, and health care utilization. Multivariate logistic regression was used to examine adjusted associations of SDB and obesity with asthma severity at 12-month follow-up. RESULTS: Among 108 subjects (mean age, 9.1±3.4 years; 45.4% African-American; 67.6% male), obesity and SDB were common, affecting 42.6% and 29.6% of subjects, respectively. After adjusting for obesity, race, and sex, children with SDB had a 3.62-fold increased odds of having severe asthma at follow-up (95% CI, 1.26-10.40). Obesity was not associated with asthma severity. CONCLUSION: SDB is a modifiable risk factor for severe asthma after 1 year of specialty asthma care. Further studies are needed to determine whether treating SDB improves asthma morbidity.

Left ventricular hypertrophy and diastolic dysfunction in children with sickle cell disease are related to asleep and waking oxygen desaturation.

Premature death and cardiac abnormalities are described in individuals with sickle cell disease (SCD), but the mechanisms are not well characterized. We tested the hypothesis that cardiac abnormalities in children with SCD are related to sleep-disordered breathing. We enrolled 44 children with SCD (mean age, 10.1 years; range, 4-18 years) in an observational study. Standard and tissue Doppler echocardiography, waking oxygen saturation averaged over 5 minutes, and overnight polysomnography were obtained in participants, each within 7 days. Eccentric left ventricular (LV) hypertrophy was present in 46% of our cohort. After multivariable adjustment, LV mass index was inversely related to average asleep and waking oxygen saturation. For every 1% drop in the average asleep oxygen saturation, there was a 2.1 g/m(2.7) increase in LV mass index. LV diastolic dysfunction, as measured by the E/E' ratio, was present in our subjects and was also associated with low oxygen saturation (sleep or waking). Elevated tricuspid regurgitant velocity (> or = 2.5 m/sec), a measure of pulmonary hypertension, was not predicted by either oxygen saturation or sleep variables with multivariable logistic regression analysis. These data provide evidence that low asleep and waking oxygen saturations are associated with LV abnormalities in children with SCD.

Prevalence of sleep disturbances in children and adolescents with chronic kidney disease.

Although sleep disorders are common in adults with chronic kidney disease, little is known about the prevalence of sleep problems in children and adolescents with chronic kidney disease and their relationship to health-related quality of life measurements. We performed a clinic-based survey of sleep habits and common symptoms of sleep disturbances in 159 school-aged patients with chronic kidney disease. Three patient groups of chronic kidney disease were assessed: group 1, those not on dialysis and not transplanted; group 2, those on dialysis; and group 3, those with a functioning renal allograft. Four symptom domains for sleep disorders were assessed: excessive daytime sleepiness; sleep disordered breathing; restless legs syndrome symptoms; and insufficient sleep. Patients and the parent-proxy also completed the Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales questionnaire. Ninety-three (93) patients (58.5%) had symptoms of a sleep disturbance. The presence of a sleep disturbance correlated with a decrease in health-related quality of life scores that was independent of the chronic kidney disease study group or estimated glomerular filtration rate. We conclude that sleep disturbances are common throughout the spectrum of chronic kidney disease in children and adolescents and are associated with diminished health-related quality of life scores.

Long-term safety and maintenance of efficacy of sodium oxybate in the treatment of narcolepsy with cataplexy in pediatric patients.

STUDY OBJECTIVES: Evaluate long-term efficacy and safety of sodium oxybate (SXB) in children and adolescents (aged 7-16 years) with narcolepsy with cataplexy. METHODS: A double-blind randomized withdrawal study was conducted. Prior to randomization, SXB-naive participants were titrated to an efficacious and tolerable dose of SXB; participants taking SXB entered on their established dose. Following a 2-week stable-dose period and 2-week, double-blind, randomized withdrawal period, participants entered an open-label period (OLP; ≤ 47 weeks). Efficacy measures during the OLP included number of weekly cataplexy attacks, cataplexy-free days, and Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD). Safety outcomes included treatment-emergent adverse events; assessments of depression, anxiety, and suicidality; and polysomnography. RESULTS: Of 106 enrolled participants, 95 entered and 85 completed the OLP. In SXB-naive participants and participants previously taking SXB, efficacy of SXB established prior to the double-blind, randomized withdrawal period was maintained throughout the OLP for number of weekly cataplexy attacks (median [quartile 1, quartile 3] change from the stable-dose period to end of the OLP: 0.0 [-2.5, 4.9] and 0.0 [-3.4, 2.6], respectively) and ESS-CHAD scores (0.0 [-3.0, 2.5] and 1.0 [-3.0, 3.0], respectively). The median (quartile 1, quartile 3) number of cataplexy-free days per week was 2.3 (0.0, 6.0) in OLP week 1 and 3.8 (0.5, 5.5) in week 48. Treatment-emergent adverse events (≥ 5%) were enuresis, nausea, vomiting, headache, decreased weight, decreased appetite, nasopharyngitis, upper respiratory tract infection, and dizziness. CONCLUSIONS: SXB demonstrated long-term maintenance of efficacy in pediatric narcolepsy with cataplexy, with a safety profile consistent with that observed in adults. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: A Multicenter Study of the Efficacy and Safety of Xyrem with an Open-Label Pharmacokinetic Evaluation and Safety Extension in Pediatric Subjects with Narcolepsy with Cataplexy; URL: https://clinicaltrials.gov/ct2/show/NCT02221869; Identifier: NCT02221869. CITATION: Lecendreux M, Plazzi G, Dauvilliers Y, et al. Long-term safety and maintenance of efficacy of sodium oxybate in the treatment of narcolepsy with cataplexy in pediatric patients. J Clin Sleep Med. 2022;18(9):2217-2227.

Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study.

STUDY OBJECTIVES: The clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial. METHODS: Participants aged ≥ 18 years with an apnea-hypopnea index ≥ 15 events/h and baseline sleepiness (Epworth Sleepiness Scale [ESS] ≥ 12) received PAP therapy. Data were collected at baseline, 1-month follow-up, and 3-months follow-up. Regression models and receiver operating characteristic curves evaluated PAP measures as predictors of ESS change and normalization (ESS < 10). RESULTS: In 119 participants (aged 49.4 ± 12.6 years, 66.4% male, 72.3% White), > 50% were PAP nonadherent per Centers for Medicare & Medicaid Services criteria at 3 months. The percentage of nights with PAP use ≥ 4 hours predicted ESS change (P = .023), but not when controlling for the apnea-hypopnea index. The percentage of nights with ≥ 4 hours and average PAP use provided the best discrimination for predicting ESS normalization; each 10% increase in PAP use ≥ 4 hours increased the odds of ESS normalization by 22% (P = .007); those using PAP ≥ 4 hours had a nearly 3-fold greater odds of ESS normalization (P = .025). PAP use for at least 4 hours and on 70% of nights provided the best balance between specificity (0.50) and sensitivity (0.73). CONCLUSIONS: Although subadherent PAP usage may still confer some benefit for patients with obstructive sleep apnea, adherence to current criteria confers the highest likelihood for ESS change and normalization. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Portable Monitoring for Diagnosis and Management of Sleep Apnea (HomePAP); URL: https://clinicaltrials.gov/ct2/show/NCT00642486; Identifier: NCT00642486. CITATION: Pascoe M, Bena J, Andrews ND, et al. Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study. J Clin Sleep Med. 2022;18(4):1027-1034.