Volume assured pressure support mode use for non-invasive ventilation in pediatrics.

There has been increasing interest in utilizing volume assured pressure support (VAPS) modes of ventilation for children, which historically had only been favored in adult populations. In addition to patients with obesity hypoventilation syndrome, newer pediatric populations for which it has recently been prescribed include congenital central hypoventilation syndrome and children with neuromuscular disease such as Duchenne muscular dystrophy and spinal muscular atrophy. Given its expanding use in pediatrics, greater familiarity with VAPS is essential for pediatric pulmonologists and sleep physicians. This review article will highlight methods of initiation for this mode, specific ventilator settings, discussion of suitable pediatric patient populations, ventilator titrations via formal polysomnograms and detailed ventilator data downloads specific interpretation. Finally, common challenges to be aware of and how to troubleshoot relevant machine alarms will be reviewed.

Sleep disordered breathing in infants identified through newborn screening with spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is a genetic disorder that may result in neuromuscular weakness and respiratory insufficiency. Gene replacement therapy has changed the trajectory of this condition, but long-term outcomes related to sleep disordered breathing are not known. METHODS: This was a retrospective review of infants with SMA identified via newborn screening who subsequently received onasemnogene abeparvovec at the Hospital for Sick Children (Ontario, Canada). Polysomnograms were conducted at the time of confirmed diagnosis as well as regularly thereafter. RESULTS: Eleven children (4 female) were identified via newborn screen (7 with 2 copies of the SMN2 gene and 4 with 3 copies of the SMN2 gene) and received onasemnogene abeparvovec at a median age of 3.6 weeks. All eleven infants met criteria for sleep disordered breathing based on their first completed polysomnograms but improved over time. Three infants required respiratory technology, including a premature infant who was prescribed nocturnal supplemental oxygen therapy for central sleep apnea and two symptomatic infants with neuromuscular weakness who required nocturnal noninvasive ventilation. We did not find a correlation between motor scores and polysomnogram parameters. CONCLUSION: Children treated with onasemnogene abeparvovec have reduced sleep disordered breathing over time. Polysomnograms revealed abnormal parameters in all children, but the clinical significance of these findings was unclear for children who were asymptomatic for sleep disordered breathing or neuromuscular weakness. These results highlight the need to evaluate both motor scores and respiratory symptoms to ensure a holistic evaluation of clinical status.

The association between sleep quality and obstructive sleep apnea with health-related quality of life in children with obesity.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and poor sleep quality are highly prevalent in children with obesity, but their individual associations with health-related quality of life (HRQOL) are unknown in this population. The primary objective was to describe the independent association of OSA and sleep quality with HRQOL in children with obesity. METHODS: This was a cross-sectional study of children with obesity at 2 tertiary care centers. Sleep quality and HRQOL were measured with the Pittsburgh Sleep Quality Index and Pediatric Quality of Life Inventory questionnaires, respectively. Multivariable regression models were created to evaluate associations between OSA and sleep quality with HRQOL. RESULTS: There were 98 children (median age 15.0 years, median body mass index z-score 3.8, 44% females). Among the study population, 49/98 (50%) children reported poor sleep quality, 41/98 (42%) children had OSA, and 52/98 (53%) children reported impaired HRQOL. Self-reported poor sleep quality was independently associated with reduced HRQOL, whereas the presence of OSA was not. Children with poor sleep quality had a reduced Pediatric Quality of Life Inventory score by 8.8 compared to children with good sleep quality (95% confidence interval, 2.6-14.9; P = .006), when adjusting for age, sex, body mass index z-score, attention-deficit/hyperactivity disorder, mood/anxiety disorder, and study site. CONCLUSIONS: In the current study of children with obesity, we found that HRQOL was more strongly associated with the self-reported experience of sleep than the presence of OSA. Clinicians should assess and optimize sleep quality as part of the evaluation for OSA in children with obesity. CITATION: Xiao L, Voutsas G, Ryan CM, Katz SL, Narang I. The association between sleep quality and obstructive sleep apnea with health-related quality of life in children with obesity. J Clin Sleep Med. 2023;19(11):1877-1883.

Understanding caregiver experiences with disease-modifying therapies for spinal muscular atrophy: a qualitative study.

OBJECTIVE: Spinal muscular atrophy (SMA) is a neuromuscular disorder that manifests with motor deterioration and respiratory complications. The paradigm of care is shifting as disease-modifying therapies including nusinersen, onasemnogene abeparvovec and risdiplam alter the disease trajectory of SMA. The objective of this study was to explore caregivers' experiences with disease-modifying therapies for SMA. DESIGN: Qualitative study including semistructured interviews with caregivers of children with SMA who received disease-modifying therapies. Interviews were audio recorded, transcribed verbatim, coded and analysed using content analysis. SETTING: The Hospital for Sick Children (Toronto, Canada). RESULTS: Fifteen family caregivers of children with SMA type 1 (n=5), type 2 (n=5) and type 3 (n=5) participated. There were two emerging themes and several subthemes (in parentheses): (1) inequities in access to disease-modifying therapies (variable regulatory approvals, prohibitively expensive therapies and insufficient infrastructure) and (2) patient and family experience with disease-modifying therapies (decision making, hope, fear and uncertainty). CONCLUSION: The caregiver experience with SMA has been transformed by the advent of disease-modifying therapies. Consistent and predictable access to disease-modifying therapies is a major concern for caregivers of children with SMA but is influenced by regulatory approvals, funding and eligibility criteria that are heterogenous across jurisdictions. Many caregivers described going to great lengths to access therapies, highlighting issues related to justice, such as equity and access. This diverse population reflects contemporary patients and families with SMA; their broad experiences may inform the healthcare delivery of other emerging orphan drugs.

Polysomnography in hospitalized children: Characteristics and clinical practice at a single tertiary care center.

BACKGROUND: Polysomnography (PSG) is the gold standard for the diagnosis of pediatric sleep-disordered breathing (SDB). However, the literature characterizing the indications for inpatient PSGs and the impact on clinical decision-making is limited. OBJECTIVE: To determine the indications, results, and outcomes for children undergoing inpatient PSGs at our institution. METHODS: We performed a retrospective review of children aged 0-18 years who underwent inpatient diagnostic PSGs between July 2018 and July 2021 at SickKids, Toronto, Canada. Baseline characteristics, indications, and management were reviewed and characterized by descriptive statistics. RESULTS: Eighty-eight inpatient PSGs were performed in 75 children (male 62.7%). Median (interquartile range) age and body mass index z-score were 1.5 (0.2, 10.8) years and 0.27 (-1.58, 2.66), respectively. The most common indication for inpatient PSG was initiation and titration of ventilation (n = 34/75, 45.3%). Of the 75 children, 48 (64%) had multiple complex chronic conditions (CCCs). Sixty children (80%) underwent a baseline PSG for either the entire night or a portion of the night. Of these studies, 54 (90%) had clinically significant SDB of which isolated obstructive sleep apnea (OSA; 17/60, 28.3%) was the most common. The following management was undertaken for the 54 patients with SDB; respiratory technology (88.9%), surgical intervention (31.5%), positional therapy (1.9%), intranasal steroids (3.7%), and no further intervention (5.6%), respectively. CONCLUSIONS: Our study highlights that inpatient PSG was an important diagnostic tool resulting in directed medical and surgical management. Future multicenter studies are needed to compare indications for inpatient PSGs across institutions to develop evidence-based clinical practice guidelines.

Long-term mechanical ventilation and transitions in care: A narrative review.

OBJECTIVES: Individuals dependent on long-term mechanical ventilation (LTMV) for their day-to-day living are a heterogenous population who go through several transitions over their lifetime. This paper describes three transitions: 1) institution/hospital to community/home, 2) pediatric to adult care, and 3) active treatment to end-of-life for ventilator-assisted individuals (VAIs). METHODS: A narrative review based on literature and the author's collective practical and research experience. Four online databases were searched for relevant articles. A manual search for additional articles was completed and the results are summarized. RESULTS: Transitions from hospital to home, pediatric to adult care, and to end-of-life for VAIs are complex and challenging processes. Although there are several LTMV clinical practice guidelines highlighting key components for successful transition, there still exists gaps and inconsistencies in care. Most of the literature and experiences reported to date have been in developed countries or geographic areas with funded healthcare systems. CONCLUSIONS: For successful transitions, the VAIs and their support network must be front-and-center. There should be a coordinated, systematic, and holistic plan (including a multi-disciplinary team), life-time follow-up, with bespoke consideration of jurisdiction and individual circumstances.

Respiratory characteristics in children with spinal muscular atrophy type 1 receiving nusinersen.

BACKGROUND: Spinal muscular atrophy type 1 (SMA1) is a neuromuscular disorder with a natural history of chronic respiratory failure and death during infancy without ventilation. Recently, disease-modifying therapies such as nusinersen have improved disease trajectory. However, objective data on the trajectory of polysomnography outcomes, the relationship between motor scores and respiratory parameters, respiratory technology dependence and healthcare utilization in children with SMA1 remain to be elucidated. METHODS: This was a retrospective observational study of children with SMA1 receiving nusinersen between October 2016 and February 2021 at two tertiary care hospitals in Canada. Baseline polysomnography data, motor scores, respiratory technology, and unanticipated healthcare utilization were examined. RESULTS: Eleven children (five females, two SMN2 copies each) were included. Median (interquartile range [IQR]) age at diagnosis was 3.6 (2.8-5.0) months and age at diagnostic polysomnogram following nusinersen initiation was 9.4 (5.3-14.0) months. Nusinersen was initiated at a median (IQR) age of 5.4 (3.4-7.6) months and 8/11 children had respiratory symptoms at that time. Diagnostic polysomnography data showed a median (IQR) central apnea-hypopnea index (AHI) of 4.1 (1.8-10.0) and obstructive AHI of 2.2 (0-8.0) events/h. We observed an inverse relationship between motor scores and central apnea-hypopnea indices. All children required ventilatory support at the end of the study period. CONCLUSION: This study showed abnormal polysomnography parameters and need for ventilation despite nusinersen suggesting ongoing need for regular monitoring with polysomnography. Understanding the respiratory disease trajectory of children undergoing treatment with nusinersen will inform decision-making regarding optimal timing of ventilatory support initiation.

Unexplained Significant Central Sleep Apnea in Infants: Clinical Presentation and Outcomes.

OBJECTIVE: Unexplained significant central sleep apnea in term infants presents as central apneas with associated oxygen desaturations requiring respiratory support and monitoring for prolonged periods. However, there is a paucity of literature describing idiopathic central sleep apnea (ICSA) in term or near-term infants. Our aim was to describe the clinical manifestations, polysomnography data, interventions, and trajectory of ICSA in infants. DESIGN: This is a retrospective study of infants (gestational age ≥ 35 weeks) who presented with significant central apneas and were subsequently diagnosed with ICSA following polysomnography and clinical investigations between January 2011 and April 2021 at a tertiary care hospital in Canada. Polysomnography data, clinical investigations, and treatments were documented. RESULTS: Eighteen infants (male, 78%; median gestational age 38 weeks) with ICSA were included. Initial polysomnograms were completed at a median (interquartile range [IQR]) age of 1.2 (0.6-1.6) months (n = 18) and follow-up polysomnograms at 12.4 (10.6-14.0) months (n = 13). Compared to baseline diagnostic polysomnograms, at follow-up there was a significant reduction in the median (IQR) central apnea-hypopnea index (26.1 [18.2-52.9] versus 4.2 [2.6-7.2] events/hour; p = 0.001), desaturation index (30.9 [12.2-57.4] versus 3.9 [3.0-7.9] events/hour; p = 0.002), average transcutaneous carbon dioxide (41.9 [40.1-47.3 versus 39.4 [37.5-42.7] mmHg; p = 0.025), and improved nadir oxygen saturation (79.8 [69.1-83.0] versus 85.5 [83.2-87.8]%; p = 0.033), respectively. Prescribed treatments included supplemental oxygen (14/18, 78%), caffeine (5/18, 28%), and noninvasive ventilation (1/18, 6%). CONCLUSIONS: Infants with significant unexplained ICSA have a favorable clinical trajectory over time. Further research is needed to understand the etiology of this rare disorder.

Scoliosis in Spinal Muscular Atrophy Type 1 in the Nusinersen Era.

Background and Objectives: The introduction of spinal muscular dystrophy (SMA)-modifying therapies, such as antisense oligonucleotide therapy, has changed the natural history of SMA. Most reports on treatment outcomes have focused on motor scores and respiratory function. The objective of this study is to document the development and progression of scoliosis in patients with SMA1 treated with nusinersen. Methods: A descriptive single-center study was conducted in patients with SMA1 who were treated with nusinersen before 6 months of age. Data were collected on patients who met criteria, including age at the first nusinersen dose, number of nusinersen doses, degree of scoliosis, respiratory parameters, feeding route, and motor scores at baseline and follow-up. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was subanalyzed using axial (AxS) and appendicular motor (ApS) scores to evaluate a possible correlation between scoliosis and axial muscle strength. Results: From our cohort, 31 percent (11/35) of patients had a diagnosis of SMA1. Sixty-three percent (7/11) met the inclusion criteria. All patients (7/7) showed initial improvement in their CHOP-INTEND scores in correlation with improvement on the ApS. Despite this, most patients did not show improvement in the AxS. Subsequently, all patients developed scoliosis in the first year of life with Cobb angles that ranged between 18° and 60°. Furthermore, total CHOP-INTEND scores had dropped in 2 patients alongside the development of a Cobb angle of >40°. Discussion: Despite the significant improvement in functional motor assessment in patients with SMA1, there is a progression of significant scoliosis despite treatment. Subsequently, lack or minimal improvement on the axial CHOP-INTEND scores may predict worsening on the total motor scores.

Risk factors for respiratory adverse events after adenoidectomy and tonsillectomy in children with down syndrome: a retrospective cohort study.

Obstructive sleep apnea syndrome is a major cause of morbidity in the Down syndrome population and is commonly treated with adenoidectomy and/or tonsillectomy (AT). However, these children are at increased risk for perioperative respiratory adverse events (PRAEs). The objective of this study was to examine risk factors for major PRAEs requiring intervention in children with Down syndrome undergoing AT and to describe their postoperative monitoring environment. This retrospective study included all children with Down syndrome aged 0-18 years who underwent a preoperative polysomnogram followed by AT at a tertiary pediatric institution. Descriptive statistics were used to summarize baseline demographic and clinical characteristics. A multivariable model for prediction of PRAEs was constructed. A priori, it was decided that minimum oxygen saturation, apnea-hypopnea index, and average oxygen saturation asleep would be included, along with medical comorbidities associated with PRAEs at p < 0.2 in univariable analyses. Fifty-eight children were included in this study; twelve had a PRAE. Cardiac disease was associated with PRAEs on univariable analysis (p = 0.03). In multivariable analysis, average oxygen saturation asleep was associated with PRAEs (OR 1.50; 95% confidence interval 1.00, 2.41; p = 0.05). For all of the remaining variables, p > 0.15. Fifty-six children were admitted for monitoring overnight; four were admitted to the intensive care unit and fifty-two were admitted to the ward. CONCLUSIONS: A multivariable model found evidence that lower average oxygen saturation while asleep was associated with PRAEs requiring intervention in children with Down syndrome. This study highlights the difficulty in predicting complications in this population. WHAT IS KNOWN: • Obstructive sleep apnea syndrome is a major cause of morbidity in the Down syndrome population and is commonly treated with adenoidectomy and/or tonsillectomy. • However, children with Down syndrome are at increased risk for perioperative respiratory adverse events (PRAEs) following adenoidectomy and/or tonsillectomy. WHAT IS NEW: • We found that a lower average oxygen saturation asleep is associated with increased odds of PRAEs, adjusting for age, total apnea-hypopnea index, cardiac comorbidity, and minimum oxygen saturation. • This study highlights the difficulty in predicting complications in this population.

Narcolepsy Treatment: Voices of Adolescents.

INTRODUCTION: Narcolepsy, characterized by excessive daytime sleepiness, is a debilitating lifelong sleep disorder for which there is no cure. Current pharmacological and nonpharmacological treatments directed toward symptom management may be suboptimal. This qualitative study explores the perspective of adolescents on therapeutic interventions for narcolepsy. METHODS: Semi-structured interviews with adolescents with narcolepsy were conducted from May to August 2019 at The Hospital for Sick Children in Toronto, Canada. Qualitative thematic analysis was utilized to generate themes emerging from the data. RESULTS: Eighteen adolescents with narcolepsy (age range = 10-17, mean age = 14.4 ± 2.0 years, 72% male) participated and 56% had cataplexy. Four prominent themes arose regarding therapeutic interventions for narcolepsy. Firstly, participants described that pharmacotherapy was moderately effective but did not fully relieve symptoms associated with narcolepsy. Secondly, while medications are the first line treatment for narcolepsy, many participants reported frustration regarding medication dependence and side effects. Thirdly, nonpharmacological strategies including scheduled sleep times and exercise were accepted and often employed. Lastly, adolescents desired more psychosocial support to address mental health sequelae of narcolepsy that were not fully managed by current treatment modalities. CONCLUSIONS: Medications were perceived as moderately effective for managing narcolepsy but almost all participants expressed concerns with taking medications due to side effects. Adolescents valued the importance of more holistic care for their narcolepsy treatment such as psychosocial support and nonpharmacological modalities. Further anticipatory guidance regarding pharmacological side effect profiles and better integration with nonpharmacological modalities are needed to improve disease control in adolescent patients.

Pediatric tracheostomy tube decannulation with or without polysomnography: A PRO-CON debate.

Determining the timing for decannulation in children with a tracheostomy is a complex process, as the appropriate timing varies based on the initial indication for the tracheostomy tube as well as individual patient characteristics. The original condition for which a tracheostomy was created may improve over time with decannulation being a very important long-term goal for many families and multidisciplinary teams. However, decannulation is an inherently risky procedure associated with morbidity and mortality. Therefore, careful planning is required to ensure the safety of the procedure. Although routine airway endoscopy is an important component of decannulation protocols, guidelines are less prescriptive regarding the definition of a complete endoscopic airway evaluation and the routine use of polysomnography. This review will summarize the important PRO and CON arguments of integrating polysomnography into pediatric decannulation protocols.

Positional device therapy for the treatment of positional obstructive sleep apnea in children: a pilot study.

BACKGROUND: There is a critical gap in identifying effective interventions for children with obstructive sleep apnea (OSA) who do not tolerate continuous positive airway pressure therapy. Positional OSA (POSA) is a common clinical phenotype whereby OSA occurs predominantly while sleeping in supine position. POSA may be amenable to treatment with a positional device, a belt worn around the chest with cushions on the back to prevent supine positioning, but no data exists in children. The primary aim of this study was to evaluate the efficacy of positional device therapy for the treatment of POSA in children. METHODS: This observational study included children aged 4-18 years with POSA and an obstructive apnea-hypopnea index (OAHI) ≥ 5 events/hour on baseline polysomnogram (PSG) who underwent a second PSG to evaluate the efficacy of a positional device. The primary outcome was the change in OAHI. RESULTS: Ten children were included (8 male, median age 11.2 years, median body mass index z-score 1.6). Compared to the baseline PSG, PSG data obtained while using a positional device showed a reduced median (interquartile range) OAHI (15.2 [8.3-25.6] versus 6.7 [1.0-13.7] events/hour respectively; p = 0.004) and percentage of total sleep time in supine position (54.4 [35.0-80.6]% versus 4.2 [1.1-25.2]% respectively; p = 0.04). Despite observed improvements in the oxygen desaturation index, these results were not statistically significant. SIGNIFICANCE AND CONCLUSIONS: In this novel pilot study, positional device therapy was effective for the treatment of POSA. Positional device therapy may potentially change clinical practice as a cost-efficient and non-invasive treatment option for POSA.

Polysomnography parameters as predictors of respiratory adverse events following adenotonsillectomy in children.

STUDY OBJECTIVES: The first-line treatment of obstructive sleep apnea syndrome in children is adenotonsillectomy, but this may result in perioperative respiratory adverse events (PRAEs). The primary aim of this study is to examine whether the McGill oximetry score (MOS) and other polysomnography parameters can predict major PRAEs following adenotonsillectomy. We secondarily evaluated the MOS interrater reliability and correlation with other polysomnography parameters. METHODS: This retrospective study included all children aged 0-18 years who underwent preoperative polysomnography between June 2010 and January 2016 prior to adenotonsillectomy at a tertiary pediatric institution. Oximetries from polysomnograms were assigned an MOS. Univariable and multivariable models for prediction of major PRAEs were constructed. MOS was correlated with polysomnography parameters and interrater reliability was evaluated. RESULTS: This study included 106 children; 15 had a major PRAE. A multivariable prediction model that combined MOS and age showed evidence for the ability to predict major PRAEs with an area under the receiver operating characteristic curve of 0.68 (95% confidence interval: 0.52, 0.84), whereby increased MOS and younger age were associated with PRAEs, but apnea-hypopnea index was not. MOS had excellent interrater reliability (κ = 0.95) and was highly correlated with oxygen saturation nadir and cumulative time percentage with oxygen saturation less than 90%. CONCLUSIONS: A prediction model including MOS and age may predict PRAEs following adenotonsillectomy. This suggests that nocturnal oximetry provides the most essential information of polysomnography measures to direct postoperative monitoring following adenotonsillectomy. CITATION: Xiao L, Barrowman N, Momoli F, et al. Polysomnography parameters as predictors of respiratory adverse events following adenotonsillectomy in children. J Clin Sleep Med. 2021;17(11):2215-2223.