Blood pressure variability in children with obesity and sleep-disordered breathing following positive airway pressure treatment.

Obese youth with sleep-disordered breathing are treated with positive airway pressure to improve sleep and cardiovascular status. While improvements in sleep parameters have been confirmed, a study by Katz et al. showed no major improvement in ambulatory blood pressure. The aim of this ancillary study was to analyze short-term blood pressure variability, following positive airway pressure treatment, as a more sensitive marker of cardiovascular health. We analyzed 24-h blood pressure variability data in 17 children, taken at baseline and after 12 months of treatment. These data were derived from an already published prospective, multicenter cohort study conducted in 27 youth (8-16 years) with obesity who were prescribed 1-year of positive airway pressure for moderate-severe sleep-disordered breathing. Significant decreases were found in 24 h systolic blood pressure (p = 0.040) and nighttime diastolic blood pressure (p = 0.041) average real variability, and diastolic blood pressure (p = 0.035) weighted standard deviation. Significant decreases were noted in nighttime diastolic blood pressure time rate variability (p = 0.007). Positive airway pressure treatment resulted in a significant decrease in blood pressure variability, suggesting a clinically significant improvement of sympathetic nerve activity in youth with obesity and sleep-disordered breathing. IMPACT: Cardiovascular variability, as measured by blood pressure variability, is improved in children following positive airway pressure treatment. Our novel findings of improved blood pressure time rate variability are the first described in the pediatric literature. Future studies aimed at analyzing target organ damage in this patient population will allow for a better understanding as to whether alterations in blood pressure variability translate to decreasing target organ damage in children, as seen in adults.

Pulmonary function in children and adolescents with sickle cell disease after nonmyeloablative hematopoietic cell transplantation.

BACKGROUND: Pulmonary complications are common in sickle cell disease (SCD). The use of standard myeloablative conditioning regimens may increase the risk of lung injury. We report serial pulmonary function testing (PFT) outcomes in children with SCD who underwent a matched-sibling donor hematopoietic cell transplantation (HCT) using nonmyeloablative (NMA) protocol. METHODS: This is a retrospective chart review describing pulmonary outcomes in pediatric patients post HCT. The conditioning regimen consisted of alemtuzumab and a single fraction of 300 cGy of total body irradiation (TBI), and sirolimus for graft-versus-host disease (GVHD) prophylaxis. Serial PFT testing was performed pre and post HCT. The evaluated pulmonary measures included: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1 ), FEV1 /FVC, and forced expiratory flow (FEF25-75 ). RESULTS: Twelve subjects were included in the analysis. All had HbSS genotype, and five of the 12 patients had one or more episodes of acute chest syndrome prior to HCT. Serial PFT measures were completed per patient. No patient was diagnosed with chronic GVHD of any organ post HCT. The baseline median FVC, FEV1 , FEV1 /FVC, and FEF25-75 were within the normal range and remained relatively unchanged post HCT. A linear mixed effects model, adjusting for gender and time from HCT, suggested no significant relationship between HCT and PFT parameters, including FVC, FEV1 , and FEV1 /FVC. Interestingly, the FEF25-75 results exhibited a shift in the means post HCT (pre-HCT 86.2% predicted and post-HCT 93.05% predicted, p-value = .018). CONCLUSION: Our study suggests that HCT in children with SCD may prevent the anticipated decline in pulmonary function over time.

Behavioral and emotional characteristics of Canadian children with obesity and moderate-severe sleep-disordered breathing treated with positive airway pressure: longitudinal changes and associations with adherence.

STUDY OBJECTIVES: Behavioral characteristics and outcomes of positive airway pressure (PAP) therapy in children with obesity and moderate-severe sleep-disordered breathing (SDB) have not been reported. Our aims were to 1) determine baseline behavioral/emotional symptoms of this population and characterize changes over time with PAP, and 2) examine associations between baseline behavioral/emotional symptoms and PAP adherence. METHODS: This multicenter prospective cohort study of children with obesity prescribed PAP for moderate-severe SDB assessed PAP adherence (≥ 4 h/night, >50% of nights, usage diaries, downloads) and compared behavioral/emotional characteristics with parent- and child-reported Conners Rating Scale (Conners) and the Child Behavior Checklist (CBCL) at baseline and 1 year after PAP prescription between adherent and nonadherent participants; scores at baseline were compared retrospectively between adherence groups. RESULTS: Twenty-four children were included (median 14.1 years [IQR:12.4,16.0]; 87.5% males). Baseline Conners and CBCL scores were elevated (parent- and child-reported Conners inattention and hyperactivity subscales and CBCL subscales [total, internalizing, externalizing]). Baseline parent-reported Conners scores were significantly more elevated in the nonadherent than adherent group (inattention: 73.3 ± 8.5 vs 60.5 ± 14.6, P = .01; hyperactivity: 70.9 ± 11.1 vs 59.1 ± 16.0, P = .05). This difference was present 1 year later for inattention (P = .01) but not for hyperactivity (P = .09). Parent-reported CBCL scores improved over 1 year in adherent but not nonadherent participants. CONCLUSIONS: We found that children with obesity and moderate-severe SDB have elevated symptoms of behavioral/emotional concerns on standardized testing. Parent-reported emotional characteristics improved in the adherent but not in the nonadherent group. Children with greater inattention/hyperactivity at baseline were less adherent to PAP, suggesting this may contribute to PAP nonadherence. CITATION: Constantin E, MacLean JE, Barrowman N, et al. Behavioral and emotional characteristics of Canadian children with obesity and moderate-severe sleep-disordered breathing treated with positive airway pressure: longitudinal changes and associations with adherence. J Clin Sleep Med. 2023;19(3):555-562.

Lower airway nitric oxide is increased in children with sickle cell disease.

OBJECTIVES: To determine alveolar and airways nitric oxide (NO) levels in children with sickle cell disease (SCD). STUDY DESIGN: Multiple flows fractional exhaled NO (FE(NO)), bronchial NO flux (J'aw(NO)), and alveolar NO concentration (Ca(NO)) were determined prospectively in 16 non-atopic children with SCD in a tertiary ambulatory clinic and compared with those in 10 children with primary ciliary dyskinesia and 22 healthy control subjects. Differences in FE(NO), J'aw(NO), and Ca(NO) were compared with mixed model analysis and Mann-Whitney tests. RESULTS: Children with SCD had reference range FE(NO) at 50 mL/sec, but FE(NO) was elevated across all flows compared with healthy control subjects (mean difference=2.10±0.91 parts per billion, P=.03). Subjects with SCD had increased J'aw(NO) (1177±533 picoliters per second versus 833±343 picolitres per second, P=.03), and Ca(NO) was no different from control subjects. In contrast, children with primary ciliary dyskinesia had decreased FE(NO) (mean difference=3.36±1.24 parts per billion, P<.01) and J'aw(NO) (507±259 picoliters per second versus 833±343 picoliters per second, P<.01). CONCLUSIONS: Lower airways NO is increased in children with SCD. Elevation of J'aw(NO) may represent dysregulation of NO metabolism or subclinical airways inflammation.

Feasibility of split night polysomnography in children to diagnose and treat sleep related breathing disorders.

STUDY OBJECTIVES: The gold standard test for diagnosis of sleep related breathing disorders (SRBD) in children is diagnostic polysomnography (PSG). This is often followed by a titration PSG to identify optimal non-invasive ventilation (NIV) pressures. Access to pediatric PSG is limited, resulting in delays to diagnosis and initiation of treatment. Split-night PSGs (snPSG) combine a diagnostic and titration PSG into a single night study. Although described in adults, the pediatric literature on this topic is sparse. The objective of this study was to describe a large cohort of children who utilized snPSG to diagnose SRBD and initiate NIV. METHODS: This multi-center study analyzed clinical and PSG data from children with SRBD who had initiated NIV following a snPSG. Data from diagnostic and titration portions of the snPSG were analyzed separately. RESULTS: The study included 165 children who initiated NIV following a snPSG. The majority of children (61.8%) were initiated on NIV for upper airway obstruction. The population included children with medical complexity, including those with central nervous system disorders (17.0%), musculoskeletal/neuromuscular disorders (12.1%), and cardiac disorders (1.2%). Moderate to severe SRBD was present in 87.2% of children with a median apnea-hypopnea index (AHI) of 16.6 events/hour (IQR: 8.2, 38.2). The median AHI was reduced on treatment to 7.6 events/hour (IQR: 3.3, 17.1), with fewer subjects meeting criteria for severe SRBD. CONCLUSIONS: snPSG is technically feasible in children, facilitating the diagnosis of SRBD and initiation of NIV, even in those with high medical complexity.

Factors related to positive airway pressure therapy adherence in children with obesity and sleep-disordered breathing.

STUDY OBJECTIVES: Positive airway pressure (PAP) is used to treat children with concurrent obesity and sleep-disordered breathing (SDB), but achieving adherence remains challenging. We aimed to identify factors associated with PAP adherence in a prospective cohort of children with obesity prescribed PAP for newly diagnosed SDB. METHODS: A questionnaire to assess factors related to PAP adherence was administered to participants and their parent ≥12 months after enrollment. Adherence (PAP use ≥4 hours/night on >50% of nights) was measured with PAP machine downloads, diaries, and physician assessments. Questionnaire responses were compared between adherent/nonadherent participants and between children/parents. Age, total and obstructive apnea-hypopnea index (OAHI), lowest oxygen saturation, and highest carbon dioxide were compared between adherent/nonadherent children with univariate differences of medians, with 95% confidence intervals. RESULTS: Fourteen children (median age: 14.3 years; 93% male; all with obstructive sleep apnea) were included. Eleven (79%) were adherent to PAP. SDB symptom improvement was reported in 9 of 14 children (64%); 8 of 14 children (57%) had positive experiences with PAP. Most children assumed an active role in PAP initiation and felt supported by the clinical team. Responses between adherent/nonadherent groups and between children/parents were similar. Oxygen saturation nadir (median difference between nonadherent and adherent groups: 8.9%; 95% confidence interval: 1.7, 16.1), but not age, apnea-hypopnea index, OAHI, or maximum carbon dioxide, was associated with PAP adherence. CONCLUSIONS: Children with obesity-related SDB with lower nocturnal oxygen saturation nadir were more likely to adhere to PAP therapy. Ensuring adequate understanding of PAP therapy and medical team support are key factors in PAP success.

The approach to Pseudomonas aeruginosa in cystic fibrosis.

Pseudomonas aeruginosa continues to be the most common pathogen in cystic fibrosis (CF) lung disease, and chronic infection with mucoid strains is associated with an accelerated decline in lung function. Although multiple factors can potentially explain the susceptibility of CF airways to this organism, their individual relevance is still largely unclear. Prevention of infection remains an important task, and hygiene measures have been successful in reducing cross-infection, but the universal presence of the organism creates an ongoing challenge, and vaccination strategies have not been highly successful to date. Over the last decade treatment strategies have shifted from controlling chronic infection to attempting to eradicate P. aeruginosa in the early stages of infection. Multiple strategies have been shown to be efficacious, but the optimal form and duration of therapy have yet to be defined. Inhaled antibiotics are a key component of maintenance therapy for chronic infection, and the spectrum of available compounds is rapidly expanding. Pulmonary exacerbations can be reduced with this strategy but usually require intravenous antibiotic therapy once they occur. Nonantibiotic approaches to address P. aeruginosa infection are currently being developed and may expand the therapeutic repertoire in the future.

Long-Term Impact of Sleep-Disordered Breathing on Quality of Life in Children With Obesity.

STUDY OBJECTIVES: (1) To determine baseline quality of life (QOL) among children with obesity and newly diagnosed moderate-severe sleep-disordered breathing (SDB) and to compare it to the reported QOL of children with obesity or SDB alone and healthy children. (2) To evaluate QOL change after 1 year. METHODS: A prospective multicenter cohort study was conducted in children (8-16 years) with obesity, prescribed positive airway pressure (PAP) therapy for moderate-severe SDB. Outcomes included parent-proxy and self-report total and subscale scores on the PedsQL questionnaire (baseline and 1-year). RESULTS: Total PedsQL scores were indicative of impaired QOL in 69% of cases based on parent-report and in 62% on self-report. Parents reported significantly lower QOL in our cohort than that reported in other studies for children with obesity or SDB alone or healthy children, on total PedsQL score and on social and psychosocial subscales. PedsQL total scores for participants were significantly higher (mean difference 7.3 ± 15.3, P = .03) than those reported by parents. Parents reported significant improvements in total PedsQL (mean change 7.29 ± 13.73, P = .04) and social functioning (mean change 17.65 ± 24.69, P = .04) scores after 1 year. No significant differences were found by children's self-report or by PAP adherence. CONCLUSIONS: QOL of children with obesity and SDB is lower than in children with obesity or SDB alone or healthy children. One year later, children reported no significant changes in QOL; parents reported significant improvements in total PedsQL and social functioning scores. PAP adherence did not significantly affect QOL change in this population. COMMENTARY: A commentary on this article appears in this issue on page 307.

Longitudinal changes in clinical characteristics and outcomes for children using long-term non-invasive ventilation.

OBJECTIVES: To describe longitudinal trends in long-term non-invasive ventilation (NIV) use in children including changes in clinical characteristics, NIV technology, and outcomes. METHODS: This was a multicenter retrospective cohort of all children started on long-term NIV from 2005 to 2014. All children 0 to 18 years who used NIV continuously for at least 3 months were included. Measures and main outcomes were: 1) Number of children starting NIV; 2) primary medical condition; 3) medical complexity defined by number of comorbidities, surgeries and additional technologies; 4) severity of sleep disordered breathing measured by diagnostic polysomnography; 5) NIV technology and use; 6) reasons for NIV discontinuation including mortality. Data were divided into equal time periods for analysis. RESULTS: A total of 622 children were included in the study. Median age at NIV initiation was 7.8 years (range 0-18 years). NIV incidence and prevalence increased five and three-fold over the 10-year period. More children with neurological and cardio-respiratory conditions started NIV over time, from 13% (95%CI, 8%-20%) and 6% (95%CI, 3%-10%) respectively in 2005-2008 to 23% (95%CI, 18%-28%) and 9% (95%CI, 6%-14%, p = 0.008) in 2011-2014. Medical complexity and severity of the sleep-disordered breathing did not change over time. Overall, survival was 95%; mortality rates, however, rose from 3.4 cases (95% CI, 0.5-24.3) to 142.1 (95% CI 80.7-250.3, p<0.001) per 1000 children-years between 2005-2008 and 2011-2014. Mortality rates differed by diagnostic category, with higher rates in children with neurological and cardio-respiratory conditions. CONCLUSIONS: As demonstrated in other centers, there was a significant increase in NIV prevalence and incidence rate. There was no increase in medical complexity or severity of the breathing abnormalities of children receiving long-term NIV over time. The mortality rate increased over time, maybe attributable to increased use of NIV for children with neurological and cardio-respiratory conditions.

The scope of sleep problems in Canadian children and adolescents with obesity.

OBJECTIVE: To determine the scope of sleep concerns, clinical features, and polysomnography (PSG) results and to identify factors that predict obstructive sleep apnea (OSA) in a cohort of children with obesity. METHODS: The study was a multicenter retrospective chart review. Data were collected from three pediatric sleep laboratories over a two year period for all children of age 8-16 years with a body mass index [BMI] ≥95th centile who were undergoing PSG. Data sources included clinical charts and PSG results. Clinical and PSG factors were examined as predictors of OSA. RESULTS: A total of 210 children met inclusion criteria, and 205 had sufficient data for analysis. The mean age was 12.5 ± 2.7 years; and 65% were male. Multiple sleep concerns and comorbidities were reported in most children (90% and 91%, respectively). OSA was identified by PSG in 44% of children; and 28% of children demonstrated moderate/severe OSA. Mouth breathing/nasal congestion (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.18-0.61), syndrome/multiple anomalies (OR = 2.4, 95% CI = 1.22-4.93), and family history of OSA (OR = 2.7, 95% CI = 1.2-5.8) or sleep problems (OR = 12.4, 95% CI = 1.5, 99.6) were the only factors predictive of OSA. Oxygen desaturation index <6 events/h measured by PSG showed an OR of 4.96 (95% CI = 2.27-10.86) for the absence of OSA. CONCLUSIONS: Children with obesity who undergo PSG are medically complex with multiple sleep concerns including a high burden of daytime symptoms; slightly less than half of children demonstrate polysomnographic features of OSA. Earlier identification of OSA, recognition of non-OSA sleep concerns, and treatment strategies to improve sleep may contribute to overall health outcomes for children with obesity.

Long-term non-invasive ventilation therapies in children: A scoping review.

Long-term non-invasive ventilation (NIV) is a common modality of breathing support used for a range of sleep and respiratory disorders. The aim of this scoping review was to provide a summary of the literature relevant to long-term NIV use in children. We used systematic methodology to identify 11,581 studies with final inclusion of 289. We identified 76 terms referring to NIV; the most common term was NIV (22%). Study design characteristics were most often single center (84%), observational (63%), and retrospective (54%). NIV use was reported for 73 medical conditions with obstructive sleep apnea and spinal muscular atrophy as the most common conditions. Descriptive data, including NIV incidence (61%) and patient characteristics (51%), were most commonly reported. Outcomes from sleep studies were reported in 27% of studies followed by outcomes on reduction in respiratory morbidity in 19%. Adverse events and adherence were reported in 20% and 26% of articles respectively. Authors reported positive conclusions for 73% of articles. Long-term use of NIV has been documented in a large variety of pediatric patient groups with studies of lower methodological quality. While there are considerable data for the most common conditions, there are fewer data to support NIV use for many additional conditions.

Insulin Resistance and Hypertension in Obese Youth With Sleep-Disordered Breathing Treated With Positive Airway Pressure: A Prospective Multicenter Study.

STUDY OBJECTIVES: There is evidence that cardiometabolic disease associated with obesity and sleep-disordered breathing (SDB) in adults is present in youth. SDB is often treated with positive airway pressure (PAP) in youth with obesity. Our aims were to determine: (1) the prevalence of cardiometabolic disease and (2) whether PAP improves markers of cardiometabolic disease, in youth with obesity and newly diagnosed moderate-severe SDB. METHODS: A prospective multicenter cohort study was conducted in youth (8 to 16 years old) with obesity, prescribed PAP therapy for newly diagnosed moderate-severe SDB. Assessments occurred at baseline and at 6 and 12 months. Outcomes included markers of insulin resistance (change in homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months = primary outcome), hypertension (24-hour ambulatory/blood pressure) and inflammation (high-sensitivity C-reactive protein: hs-CRP). RESULTS: Twenty-seven participants were enrolled. Of those with baseline testing available, 10/25 (40%) had HOMA-IR above the 97th percentile, 10/23 (44%) were hypertensive, 16/23 (70%) had loss of nocturnal blood pressure dip and hs-CRP was elevated in 16/27 (64%). There were no significant changes over time in markers of metabolic dysfunction or blood pressure, nor between PAP-adherent and non-adherent subgroups. CONCLUSIONS: In youth with obesity and SDB, metabolic dysfunction and hypertension were highly prevalent. There were no statistically significant improvements in cardiometabolic markers 1 year after the prescription of PAP therapy, although clinically relevant improvements were seen in insulin resistance and systolic blood pressure load, important predictors of future risk of cardiovascular disease. Larger, longer-term studies are needed to determine whether PAP improves cardiometabolic outcomes in obese youth. COMMENTARY: A commentary on this article appears in this issue on page 1025.

Long-term non-invasive ventilation therapies in children: a scoping review protocol.

INTRODUCTION: Non-invasive ventilation (NIV) in children has become an increasingly common modality of breathing support where pressure support is delivered through a mask interface or less commonly through other non-invasive interfaces. At this time, NIV is considered a first-line option for ventilatory support of chronic respiratory insufficiency associated with a range of respiratory and sleep disorders. Previous reviews on the effectiveness, complications and adherence to NIV treatment have lacked systematic methods. The purpose of this scoping review is to provide an overview of the evidence for the use of long-term NIV in children. METHODS AND ANALYSIS: We will use previously established scoping methodology. Ten electronic databases will be searched to identify studies in children using NIV for longer than 3 months outside an intensive care setting. Grey literature search will include conference proceedings, thesis and dissertations, unpublished trials, reports from regulatory agencies and manufacturers. Two reviewers will independently screen titles and abstracts for inclusion, followed by full-text screening of potentially relevant articles to determine final inclusion. Data synthesis will be performed at three levels: (1) an analysis of the number, publication type, publication year, and country of publication of the studies; (2) a summary of the study designs, outcomes measures used; (3) a thematic analysis of included studies by subgroups. ETHICS AND DISSEMINATION: This study will provide a wide and rigorous overview of the evidence on the use of long-term NIV in children and provide critical information for healthcare professionals and policymakers to better care for this group of children. We will disseminate our findings through conference proceedings and publications, and evaluate the results for further systematic reviews and meta-analyses.