Child Interstitial Lung Disease in an Infant with Surfactant Protein C Dysfunction due to c.202G>T Variant (p.V68F).

For newborns suspected having childhood interstitial lung disease (ChILD), the sequencing of genes encoding surfactant proteins is recommended. However, it is still difficult to interpret the clinical significance of those variants found. We report a full-term born female infant who presented with respiratory distress and failure to thrive at 2 months of age and both imaging and lung biopsy were consistent with ChILD. Her genetic test was initially reported as a variant of unknown significance in surfactant protein C (c.202G > T, p.V68F), which was modified later as likely pathogenic after reviewing a report of the same variant as causing ChILD. The infant was placed on noninvasive ventilation and treated with IV Methylprednisolone, Hydroxychloroquine, and Azithromycin but did not show significant clinical and radiological improvement underwent tracheostomy and is awaiting lung transplantation at 8 months of age. The challenges interpreting the genetic results are discussed.

Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.

Respiratory Distress: Three Patient Cases.

As mentioned in the January 2022 Pediatrics in Review Commentary, we now present three patients who have a common chief complaint followed by 5 questions for CME credit. All three cases have discussions on presentation, the differential diagnosis, and management that collectively serve as a Review article. The common theme here is that all three patients have difficulty breathing. We hope you will enjoy this review format.

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans.

Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO2) and percentage time SaO2 < 90%] and a secondary trait (respiratory event duration) in a Hispanic/Latino American population study of 11 575 individuals with significant variation in ancestral background. Linear mixed models were performed using previously inferred African, European and Amerindian local genetic ancestry markers. Global African ancestry was associated with a lower AHI, higher SaO2 and shorter event duration. Admixture mapping analysis of the primary OSA traits identified local African ancestry at the chromosomal region 2q37 as genome-wide significantly associated with AHI (P < 5.7 × 10-5), and European and Amerindian ancestries at 18q21 suggestively associated with both AHI and percentage time SaO2 < 90% (P < 10-3). Follow-up joint ancestry-SNP association analyses identified novel variants in ferrochelatase (FECH), significantly associated with AHI and percentage time SaO2 < 90% after adjusting for multiple tests (P < 8 × 10-6). These signals contributed to the admixture mapping associations and were replicated in independent cohorts. In this first admixture mapping study of OSA, novel associations with variants in the iron/heme metabolism pathway suggest a role for iron in influencing respiratory traits underlying OSA.

Vaping Associated Pulmonary Nontuberculous Mycobacteria.

INTRODUCTION: E-cigarette or vaping product use associated lung injury (EVALI) has been an important health risk in both children and adults. The pathophysiology of EVALI is not well understood. However, it is speculated that certain substances such as Vitamin E Acetate (VEA), particularly in marijuana containing vape cartridges may result in lung injury and lead to respiratory dysfunction. EVALI is often seen in the absence of infections, but it has been found to be associated with both fungal and bacterial infections. Like EVALI, nontuberculous mycobacteria (NTM) pulmonary disease is also on the rise, but is primarily reported in immunocompromised individuals. Here, we present three immunocompetent individuals wherein pulmonary NTM infection co-occurred with vaping. METHODS: Medical information including patient history, laboratory, and radiograph reports were abstracted from electronic medical records from participating institutions located in the Bronx, NY, Philadelphia, PA, and Lexington, KY. RESULTS: All three cases were otherwise immunocompetent individuals with a significant history of vaping either nicotine and/or marijuana containing products. The pathogens isolated include Mycobacterium avium complex, M. xenopi, and M. gordonae. All three patients were treated for NTM. CONCLUSION: There is little reported on the association between vaping and NTM. It is possible that vaping may have rendered these individuals to be more susceptible to NTM colonization and infection. The possible mechanisms of vaping lung injury and pulmonary NTM are discussed.

Evaluation and Management of Children with Obstructive Sleep Apnea Syndrome.

Obstructive sleep apnea syndrome (OSAS) is a common pediatric disorder characterized by recurrent events of partial or complete upper airway obstruction during sleep which result in abnormal ventilation and sleep pattern. OSAS in children is associated with neurobehavioral deficits and cardiovascular morbidity which highlights the need for prompt recognition, diagnosis, and treatment. The purpose of this state-of-the-art review is to provide an update on the evaluation and management of children with OSAS with emphasis on children with complex medical comorbidities and those with residual OSAS following first-line treatment. Proposed treatment strategies reflecting recommendations from a variety of professional societies are presented. All children should be screened for OSAS and those with typical symptoms (e.g., snoring, restless sleep, and daytime hyperactivity) or risk factors (e.g., neurologic, genetic, and craniofacial disorders) should undergo further evaluation including referral to a sleep specialist or pediatric otolaryngologist and overnight polysomnography, which provides a definitive diagnosis. A cardiology and/or endocrinology evaluation should be considered in high-risk children. For the majority of children, first-line treatment is tonsillectomy with or without adenoidectomy; however, some children exhibit multiple levels of airway obstruction and may require additional evaluation and management. Anti-inflammatory medications, weight loss, and oral appliances may be appropriate in select cases, particularly for mild OSAS. Following initial treatment, all children should be monitored for residual symptoms and polysomnography may be repeated to identify persistent disease, which can be managed with positive airway pressure ventilation and additional surgical approaches if required.

The Effects of Obstructive Sleep Apnea Syndrome on the Dentate Gyrus and Learning and Memory in Children.

Obstructive sleep apnea syndrome (OSAS) is associated with intermittent hypoxia and sleep loss. In children, impairments of cognitive function are important manifestations, but the underlying pathology is unknown. We hypothesized that OSAS would affect the dentate gyrus, a hippocampal subdivision essential to neurogenesis and cognition, and that this impact would further affect cognitive function in children. In children with OSAS (n = 11) and control subjects (n = 12; age and sex matched), we performed diffusion tensor imaging and structural MRI, polysomnography, and neuropsychological assessments. We found that OSAS was associated with decreased mean diffusivity of the left dentate gyrus (p = 0.002; false discovery rate corrected; adjusting for sex, age, and body mass index), showing a large effect size (partial η2 = 0.491), but not with any other structural measures across the brain. Decreased dentate gyrus mean diffusivity correlated with a higher apnea hypopnea index (Spearman's r = -0.50, p = 0.008) and a greater arousal index (r = -0.44, p = 0.017). OSAS did not significantly affect neuropsychological measures (p values >0.5); however, a lower verbal learning score correlated with lower dentate gyrus mean diffusivity (r = 0.54, p = 0.004). Path analysis demonstrated that dentate gyrus mean diffusivity mediates the impact of OSAS on verbal learning capacity. Finally, the diagnostic accuracy of a regression model based on dentate gyrus mean diffusivity reached 85.8% (cross validated). This study demonstrates a likely pathway of effects of OSAS on neurocognitive function in children, as well as potential utility of the dentate gyrus mean diffusivity as an early marker of brain pathology in children with OSAS.SIGNIFICANCE STATEMENT In this study we investigate the relationships between dentate gyrus structure, hippocampus-dependent cognition, and obstructive sleep apnea syndrome (OSAS). We demonstrate lower mean diffusivity of the dentate gyrus in children with OSAS, which correlates with a lower verbal learning and memory score. This study provides new evidence of disrupted microstructure of the dentate gyrus in children with OSAS that may help explain some of the neurocognitive deficits described in these children.

Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.

An Official American Thoracic Society Clinical Practice Guideline: Pediatric Chronic Home Invasive Ventilation.

BACKGROUND: Children with chronic invasive ventilator dependence living at home are a diverse group of children with special health care needs. Medical oversight, equipment management, and community resources vary widely. There are no clinical practice guidelines available to health care professionals for the safe hospital discharge and home management of these complex children. PURPOSE: To develop evidence-based clinical practice guidelines for the hospital discharge and home/community management of children requiring chronic invasive ventilation. METHODS: The Pediatric Assembly of the American Thoracic Society assembled an interdisciplinary workgroup with expertise in the care of children requiring chronic invasive ventilation. The experts developed four questions of clinical importance and used an evidence-based strategy to identify relevant medical evidence. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to formulate and grade recommendations. RESULTS: Clinical practice recommendations for the management of children with chronic ventilator dependence at home are provided, and the evidence supporting each recommendation is discussed. CONCLUSIONS: Collaborative generalist and subspecialist comanagement is the Medical Home model most likely to be successful for the care of children requiring chronic invasive ventilation. Standardized hospital discharge criteria are suggested. An awake, trained caregiver should be present at all times, and at least two family caregivers should be trained specifically for the child's care. Standardized equipment for monitoring, emergency preparedness, and airway clearance are outlined. The recommendations presented are based on the current evidence and expert opinion and will require an update as new evidence and/or technologies become available.

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans.

RATIONALE: Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability. OBJECTIVES: To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts. METHODS: Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration. MEASUREMENTS AND MAIN RESULTS: Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 × 10-8 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10-8 for respiratory event duration) and seven additional loci were identified with suggestive significance (P < 5 × 10-7). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility. CONCLUSIONS: These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.

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.).

Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. METHODS: The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008-2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18-74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). RESULTS: Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity. CONCLUSIONS: Impairment in glucose homeostasis was associated with lower HRV in Hispanic/Latino adults without diabetes, most prominently in men and individuals with abdominal adiposity. These results suggest that reduced cardiac autonomic function is associated with metabolic impairments before onset of overt diabetes in certain subgroups, offering clues for the pathophysiologic processes involved as well as opportunity for identification of those at high risk before autonomic control is manifestly impaired.

Sleep-disordered breathing in Hispanic/Latino individuals of diverse backgrounds. The Hispanic Community Health Study/Study of Latinos.

RATIONALE: Hispanic/Latino populations have a high prevalence of cardiovascular risk factors and may be at risk for sleep-disordered breathing (SDB). An understanding of SDB among these populations is needed given evidence that SDB increases cardiovascular risk. OBJECTIVES: To quantify SDB prevalence in the U.S. Hispanic/Latino population and its association with symptoms, risk factors, diabetes, and hypertension; and to explore variation by sex and Hispanic/Latino background. METHODS: Cross-sectional analysis from the baseline examination of the Hispanic Community Health Study/Study of Latinos. MEASUREMENTS AND MAIN RESULTS: The apnea-hypopnea index (AHI) was derived from standardized sleep tests; diabetes and hypertension were based on measurement and history. The sample of 14,440 individuals had an age-adjusted prevalence of minimal SDB (AHI ≥ 5), moderate SDB (AHI ≥ 15), and severe SDB (AHI ≥ 30) of 25.8, 9.8, and 3.9%, respectively. Only 1.3% of participants reported a sleep apnea diagnosis. Moderate SDB was associated with being male (adjusted odds ratio, 2.7; 95% confidence interval, 2.3-3.1), obese (16.8; 11.6-24.4), and older. SDB was associated with an increased adjusted odds of impaired glucose tolerance (1.7; 1.3-2.1), diabetes (2.3; 1.8-2.9), and hypertension. The association with hypertension varied across background groups with the strongest associations among individuals of Puerto Rican and Central American background. CONCLUSIONS: SDB is prevalent in U.S. Latinos but rarely associated with a clinical diagnosis. Associations with diabetes and hypertension suggest a large burden of disease may be attributed to untreated SDB, supporting the development and evaluation of culturally relevant detection and treatment approaches.

Eating behavior by sleep duration in the Hispanic Community Health Study/Study of Latinos.

Sleep is an important pillar of health and a modifiable risk factor for diabetes, stroke and obesity. Little is known of diet and sleep patterns of Hispanics/Latinos in the US. Here we examine eating behavior as a function of sleep duration in a sub-sample of 11,888 participants from the Hispanic Community Health Study/Study of Latinos, a community-based cohort study of Hispanics aged 18-74 years in four US cities. Using a cross-sectional probability sample with self-report data on habitual sleep duration and up to two 24-h dietary recalls, we quantified the Alternative Healthy Eating Index (AHEI-2010) score, a measure of diet quality, and intake of selected nutrients related to cardiovascular health. Linear regression models were fit to estimate least-square means of usual nutrient intake of saturated fats, potassium density, fiber, calcium, caffeine and the AHEI-2010 score by sleep duration adjusting for age, sex, Hispanic/Latino background, income, employment status, education, depressive symptomology, and years lived in the US. Distribution of calories over the day and association with sleep duration and BMI were also examined. Short sleepers (≤6 h) had significantly lower intake of potassium, fiber and calcium and long sleepers (≥9 h) had significantly lower intake of caffeine compared to others sleepers after adjusting for covariates. However no difference in the AHEI-2010 score was seen by sleep duration. Significantly more long sleepers, compared to intermediate and short sleepers, reported having ≥30% total daily calories before bedtime. Not consuming a snack or meal within 3 h before bedtime was associated with higher AHEI-2010 scores. These findings identify novel differences in dietary patterns by sleep duration in a Hispanic/Latino cohort in the U.S. CLINICALTRIALS. GOV IDENTIFIER: NCT02060344.

Respiratory muscle force and lung volume changes in a population of children with sickle cell disease.

Sickle cell disease (SCD) is a disorder known to impact the respiratory system. We sought to identify respiratory muscle force and lung volume relationships in a paediatric SCD population. Thirty-four SCD-SS subjects underwent pulmonary function testing. Height, weight, age, and gender-adjusted percent predicted maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values were compared to spirometry and lung volumes. Statistical analyses were performed using Pearson's correlation coefficient and paired two-tailed t-test. The mean ± standard deviation (SD) MIP and MEP was 69·6 ± 31·6 cm H2 O and 66·9 ± 22·9 cm H2 O, respectively, and mean ± SD percent predicted MIP (101·3 ± 45·9) exceeded MEP (72·1 ± 26·0) (P = 0·002). MIP correlated with forced vital capacity (FVC; r = 0·51, P = 0·001) and TLC (r = 0·54, P < 0·0001). MEP also correlated with FVC (r = 0·43, P = 0·011) and total lung capacity (TLC; r = 0·42, P = 0·013). Pearson's correlation coefficient testing yielded relationships between MIP and MEP (r = 0·64, P < 0·0001). SCD-SS patients showed correlations between respiratory muscle force and lung volume, and reduced percent predicted expiratory muscle force compared to inspiratory muscle force. Respiratory muscle strength may affect lung volumes in these patients, and expiratory muscles may be more susceptible than the diaphragm to SCD-induced vaso-occlusive damage.

Novel retrospective, respiratory-gating method enables 3D, high resolution, dynamic imaging of the upper airway during tidal breathing.

PURPOSE: A retrospective, respiratory-gated technique for measuring dynamic changes in the upper airway over the respiratory cycle was developed, with the ultimate goal of constructing anatomically and functionally accurate upper airway models in obstructive sleep apnea patients. METHODS: Three-dimensional cine, retrospective respiratory-gated, gradient echo imaging was performed in six adolescents being evaluated for polycystic ovary syndrome, a disorder with a high obstructive sleep apnea prevalence. A novel retrospective gating scheme, synchronized to flow from a nasal cannula, limited image acquisition to predefined physiological ranges. Images were evaluated with respect to contrast, airway signal leakage, and demonstration of dynamic airway area changes. RESULTS: Two patients were diagnosed with obstructive sleep apnea. Motion artifacts were absent in all image sets. Scan efficiency ranged from 48 to 88%. Soft tissue-to-airway contrast-to-noise ratio varied from 6.1 to 9.6. Airway signal leakage varied between 10 and 17% of soft tissue signal. Automated segmentation allowed calculation of airway area changes over the respiratory cycle. In one severe apnea patient, the technique allowed demonstration of asynchronous airway expansion and contraction above and below a severe constriction. CONCLUSIONS: Retrospective, respiratory gated imaging of the upper airway has been demonstrated, utilizing a gating algorithm to ensure acquisition over specified ranges of respiratory rate and tidal volume.

The association of overweight and obesity with spirometric values in minority children referred for asthma evaluation.

BACKGROUND: Overweight, obesity, and asthma are more prevalent in minority children; yet, the association of overweight and obesity with spirometric values in asthmatic minorities is not well characterized. OBJECTIVE: To study the relationship between weight, ethnicity, and spirometric values in children referred for asthma evaluation to a large inner-city hospital in Bronx, NY. METHODS: Retrospective review of spirometry done at the first pulmonary clinic visit of 980 asthmatic children, aged 7-20 years, was conducted. Linear regression analysis was performed to elucidate the association of overweight and obesity with pulmonary function among Whites, African Americans, and Hispanics compared with their normal weight counterparts. RESULTS: More African Americans (58%) and Hispanics (65.4%) were overweight and obese than Whites (51.2%) (p < .05). Compared with their normal weight counterparts, percent forced expiratory volume in the 1st second (FEV(1))/forced vital capacity (FVC) ratio was lower in both overweight and obese African Americans (2.99%, p < .05 and 3.56%, p < .01, respectively) and Hispanics (2.64%, p < .05 and 2.36%, p < .05, respectively); these differences were found in obese (3.73%, p < .05) but not in overweight (0.68%, p = .7) Whites. CONCLUSIONS: FEV(1)/FVC ratio was lower in both overweight and obese African American and Hispanic children, while this association was present only among obese Whites compared with their normal weight counterparts. These results suggest that spirometric measures of lower airway obstruction decrease with smaller weight increments in minority children when compared with White children. In the context of the higher prevalence of overweight and obesity among African Americans and Hispanics, our findings offer one potential explanation for increased asthma among minority children.

Cortical thickness and hippocampal volume in adolescent children with obstructive sleep apnea.

STUDY OBJECTIVES: Intermittent hypoxia and sleep fragmentation due to obstructive sleep apnea (OSA) may contribute to oxidative tissue damage and apoptotic neuronal cell death, inflammation, and intracellular edema in the brain. We examined whether OSA in overweight and obese adolescent children is associated with cortical thickness and hippocampal structure compared to overweight and obese controls and whether OSA severity is associated with measures of brain integrity. METHODS: We calculated cortical thickness and hippocampal subfield volumes from T1-weighted images of 45 controls (age 15.43 ±â€…1.73 years, 21 male) and 53 adolescent children with OSA (age 15.26 ±â€…1.63 years, 32 male) to investigate the association of childhood OSA with the alteration of cortical structure and hippocampal subfield structural changes. In addition, we investigated the correlation between OSA severity and cortical thickness or hippocampal subfield volume using Pearson's correlation analysis. RESULTS: We found cortical thinning in the right superior parietal area of adolescent children with OSA (cluster size 32.29 mm2, cluster-wise corrected p-value = .030) that was negatively correlated with apnea-hypopnea index (AHI) (R=-0.27, p-value = .009) and arousal index (R=-0.25, p-value = .014). In addition, the volume of the right subiculum-head area of the hippocampus of adolescent children with OSA was larger than controls (0.19 ±â€…0.02 ml vs. 0.18 ±â€…0.02 ml, ß = 13.79, false discovery rate corrected p-value = .044), and it was positively correlated with AHI (R = 0.23, p-value = .026) and arousal index (R = 0.31, p-value = .002). CONCLUSIONS: Our findings provide evidence for OSA-associated brain structure alterations in adolescent children prior to the onset of treatment that likely have important implications for timely intervention and continued monitoring of health outcomes.

Upper airway structure and body fat composition in obese children with obstructive sleep apnea syndrome.

RATIONALE: Mechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood. OBJECTIVES: The aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS. METHODS: Magnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS. MEASUREMENTS AND MAIN RESULTS: We studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues. CONCLUSIONS: Upper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.

Severe central sleep apnea in a child with biallelic variants in NALCN.

The sodium leak channel, nonselective (NALCN), is necessary for the proper function of the neurons that play an important role in the sleep-wake cycle and regulation of breathing patterns during wakefulness and sleep. We report a 38-month-old male with developmental delay, hypotonia, and severe central sleep apnea with periodic breathing requiring noninvasive ventilation during sleep, who was found to have novel biallelic pathogenic variants in NALCN. A review of the literature illustrates 17 additional children with biallelic variants in the NALCN gene. The clinical and sleep manifestations of these children are discussed. CITATION: Maselli K, Park H, Breilyn MS, Arens R. Severe central sleep apnea in a child with biallelic variants in NALCN. J Clin Sleep Med. 2022;18(10):2507-2513.