A Feasibility Randomized Controlled Trial of Prehabilitation During Neoadjuvant Chemotherapy for Women with Breast Cancer: A Mixed Methods Study.

BACKGROUND: Limited data exist regarding the role of multimodal prehabilitation during neoadjuvant chemotherapy (NACT) for breast cancer. Determining large trial feasibility and identifying signals of prehabilitation benefit are needed. PATIENTS AND METHODS: We conducted a randomized controlled feasibility trial of multimodal prehabilitation versus usual care during NACT among women diagnosed with non-metastatic breast cancer. Intervention participants received an individualized exercise program, dietetic support, and stress management counseling during NACT. The trial assessed feasibility via rates of recruitment, attrition, adherence, and study-related adverse events. Physical fitness (Six Minute Walk Test, grip strength, anthropometrics) and patient-reported outcomes were assessed at baseline, after NACT completion, and 6 months after surgery as exploratory outcomes, and analyzed using linear mixed effects models. Qualitative data were collected from a subsample to understand feasibility and acceptability of prehabilitation. RESULTS: A total of 72 participants were enrolled from the 123 eligible patients (recruitment rate of 53%). There was a 13% attrition rate and no intervention-related adverse events. Participants in the prehabilitation group had better 6-min walk distance at the post-chemotherapy timepoint [between group difference of 49.43 m, 95% confidence interval (CI) - 118.1, 19.2] and at the post-surgery timepoint (27.3, 95% CI -96.8, 42.2) compared with the control group. Prehabilitation participants reported better quality of life, less fatigue, and improved physical activity levels compared with usual care participants. Interviews revealed that the intervention had a positive impact on the treatment experience. CONCLUSIONS: This study demonstrated feasibility and improvement in physical and psychosocial outcomes. Larger trials assessing intervention efficacy to confirm indications of prehabilitation benefit are warranted.

Heated humidified high flow nasal cannula therapy in children with obstructive sleep apnea: A randomized cross-over trial.

OBJECTIVE/BACKGROUND: Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in children with obesity and/or underlying medical complexity. The first line of therapy, adenotonsillectomy (AT), does not cure OSA in more than 50% of these children. Consequently, continuous positive airway pressure (CPAP) is the main therapeutic option but adherence is often poor. A potential alternative which may be associated with greater adherence is heated high-flow nasal cannula (HFNC) therapy; however, its efficacy in children with OSA has not been systematically investigated. The study aimed to compare the efficacy of HFNC with CPAP to treat moderate-to-severe OSA with the primary outcome measuring the change from baseline in the mean obstructive apnea/hypopnea index (OAHI). PARTICIPANTS/METHODS: This was a single-blinded randomized, two period crossover trial conducted from March 2019 to December 2021 at a Canadian pediatric quaternary care hospital. Children aged 2-18 years with obesity and medical complexity diagnosed with moderate-to-severe OSA via overnight polysomnography and recommended CPAP therapy were included in the study. Following diagnostic polysomnography, each participant completed two further sleep studies; a HFNC titration study and a CPAP titration study (9 received HFNC first, and 9 received CPAP first) in a random 1:1 allocation order. RESULTS: Eighteen participants with a mean ± SD age of 11.9 ± 3.8 years and OAHI 23.1 ± 21.7 events/hour completed the study. The mean [95% CI] reductions in OAHI (-19.8[-29.2, -10.5] vs. -18.8 [-28.2, -9.4] events/hour, p = 0.9), nadir oxygen saturation (7.1[2.2, 11.9] vs. 8.4[3.5, 13.2], p = 0.8), oxygen desaturation index (-11.6[-21.0, -2.3] vs. -16.0[-25.3, -6.6], p = 0.5) and sleep efficiency (3.5[-4.8, 11.8] vs. 9.2[0.9, 15.5], p = 0.2) with HFNC and CPAP therapy were comparable between conditions. CONCLUSION: HFNC and CPAP therapy yield similar reductions in polysomnography quantified measures of OSA severity among children with obesity and medical complexities. TRIAL REGISTRATION: NCT05354401 ClinicalTrials.gov.

Evaluating symptoms and polysomnographic findings among male and female children with obesity with and without obstructive sleep apnea.

OBJECTIVE: Limited data regarding sex-based differences in the presentation and phenotype of obstructive sleep apnea (OSA) exists among children with obesity. The study objectives were to compare reported symptoms and polysomnogram (PSG) findings between children with obesity 1) with and without OSA and 2) males and females with OSA. PATIENTS/METHODS: This cross-sectional study included children with obesity, aged 8-18 years, with a diagnostic PSG between 2015 and 2021, referred for evaluating sleep-related breathing. Patient demographics, anthropometrics, and PSG data were recorded. Symptoms were evaluated using Epworth Sleepiness Scale and Pediatric Sleep Questionnaire. Pubertal staging was collected using Tanner Stage questionnaire. PSG parameters, symptoms and pubertal stage were compared between sexes with and without OSA. RESULTS: Of 148 children, 61 (41%) had OSA. Within the OSA group, 41/62 (69%) were male (p = 0.002). Males with OSA reported higher Pediatric Sleep Questionnaire scores compared to males without OSA (0.38 ± 0.2 vs 0.23 ± 0.1; p = 0.002). Males with OSA reported more trouble breathing (p = 0.04) and mouth breathing (p = 0.008) compared to females with OSA. Females with OSA showed longer sleep onset latency (45.8 ± 40.6 min vs 22.4 ± 26.7; p = 0.02) and higher supine obstructive-apnea hypopnea index (32.9 ± 31.1 vs 20.4 ± 18.4 events/hour; p = 0.02) compared to males with OSA. A significant interaction was found between male sex and waist-to-height ratio (ß = 15.34, R2 = 0.18, p = 0.05). CONCLUSIONS: Sex differences in symptoms and phenotype of OSA exist among children with obesity. Such information is beneficial for early diagnosis and management to mitigate adverse outcomes and comorbidities.

To Wear or Not Wear the Mask: Decline in Positive Airway Pressure Usage in Children with Sleep Disordered Breathing During the COVID-19 Pandemic.

Purpose: Positive airway pressure (PAP) therapy is an effective treatment prescribed to children with sleep disordered breathing (SDB); however, PAP adherence remains challenging. Given that COVID-19 pandemic continues to impact sleep and daily life, the aim of this study was to evaluate longitudinal trajectory of PAP usage in children during the COVID-19 pandemic. Patients and Methods: This was a retrospective study. Children aged 1-18 years with SDB prescribed PAP at The Hospital for Sick Children (Toronto, Canada) were evaluated for PAP adherence. Demographics, medical history and PAP adherence data during four consecutive 3-month time periods from December 2019 to December 2020 were collected. These four time periods included i) prior to COVID-19 lockdown, ii) during the first three months of lockdown, iii) summer and iv) return to school period. Percentage of days where PAP was used for ≥4 hours and average nightly usage of PAP were primary outcomes. Results: A total of 149 children (61.7% male, mean (±SD) age=12.8 ± 4.1 years, BMI (±SD) z-score=1.45±1.43) were enrolled. Compared to prior to lockdown, the median (IQR) of percentage of PAP usage ≥4 hours and average nightly usage of PAP declined significantly during the summer and return to school periods (p<0.001 for all). By the end of the return to school period, only 69/149 (46%) showed sustained PAP usage and 80/149 (54%) had decreased PAP usage. Obesity was a risk factor for a decline in PAP usage after returning to school (ß=-15.36, p=0.03). Conclusion: Compared to COVID-19 pre-pandemic PAP usage, there was a significant decline in PAP usage across COVID-19 pandemic. There is critical under usage of PAP in children diagnosed with SDB, resulting in an urgent need to address barriers to mitigate poor adherence to PAP long-term. Targeted strategies are required to optimize PAP adherence in children with SDB.

Chewing gum: alternative therapy to oxygen intolerance.

Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare complex disorder associated with alterations in the endocrine system, autonomic nervous system, and respiratory system. Previously published case reports and studies have noted sleep-disordered breathing in patients with ROHHAD syndrome. Nocturnal respiratory manifestations, which if untreated early by respiratory support, may cause cardiorespiratory arrest and a life-threatening condition. More recently, it has been recognized that children with ROHHAD syndrome have central pauses during wakefulness associated with intermittent oxygen desaturations. We report novel findings of a child with ROHHAD syndrome displaying an irregular breathing pattern and significant central pauses associated with oxygen desaturations during wakefulness, whose respiratory status improved while chewing gum. This was used as an alternative to supplemental oxygen therapy. CITATION: Sunkonkit K, Selvadurai S, Yeh EA, Hamilton J, Narang I. Chewing gum: alternative therapy to oxygen intolerance. J Clin Sleep Med. 2022;18(6):1723-1726.

The impact of the COVID-19 pandemic on positive airway pressure usage in children with sleep-disordered breathing.

PURPOSE: To evaluate the impact of the COVID-19 pandemic on non-invasive positive airway pressure (PAP) usage among children with sleep-disordered breathing (SDB). METHODS: PAP usage data in children with SDB aged 1 to 18 years old at The Hospital for Sick Children, Canada, were analyzed. The PAP usage data were recorded for 3 months prior to and 3 months following the COVID-19 lockdown in Ontario, Canada. The primary outcomes of interest were (i) percentage of days that PAP was used for ≥ 4 h and (ii) average daily usage of PAP based on days when PAP was used. RESULTS: A total of 151 children were included. The mean (± SD) age and BMI were 12.6 ± 4.1 years and 28.7 ± 12.4 kg/m2, respectively. The median (IQR) percentage of days of PAP usage for ≥ 4 h and average nightly PAP usage was significantly higher during compared with prior to the pandemic (76.7 [19.0-94.0] vs 62.0 [15.5-89.0]%, p = 0.02, and 406.0 [244.0-525.0] vs 367.0 [218.0-496.0] min, p = 0.006, respectively). Within this cohort, 95/151 (63%) children with SDB showed increased PAP usage and 56/151 (37%) either decreased the amount of time they used PAP or stopped PAP use altogether. CONCLUSIONS: COVID-19 pandemic has provided opportunities for increased PAP usage in a significant number of children with SDB. A subset of children with prior evidence for suboptimal PAP usage showed further decreases in PAP usage during the pandemic. This information is critical for clinicians to provide anticipatory guidance to encourage PAP usage both during the pandemic and beyond.

Sleep-disordered breathing, respiratory patterns during wakefulness and functional capacity in pediatric patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation syndrome.

OBJECTIVE: To characterize the clinical presentation of sleep-disordered breathing and respiratory patterns at rest and during a 6-min walk test (6MWT) in children with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome. METHODS: Retrospective study of children with ROHHAD who had a diagnostic baseline polysomnography, daytime cardiorespiratory monitoring at rest and a 6MWT. Polysomnography data were also compared with body mass index-, age-, and sex-matched controls. RESULTS: Of the eight children with ROHHAD, all eight (100%) had obstructive sleep apnea (OSA) and 2/8 (25%) had nocturnal hypoventilation (NH) on their baseline polysomnography. Comparing the ROHHAD group to the control group, there were no significant differences in the median (interquartile range [IQR]) obstructive apnea-hypopnea index (11.1 [4.3-58.4] vs. 14.4 [10.3-23.3] events/h, respectively; p = .78). However, children with ROHHAD showed a significantly higher desaturation index compared to the control group (37.9 [13.7-59.8] vs. 14.7 [4.3-27.6] events/h; p = .05). While awake at rest, some children with ROHHAD experienced significant desaturations associated with central pauses. During the 6MWT, no significant desaturations were observed, but two children showed moderate functional limitation. CONCLUSIONS: Among children with ROHHAD, respiratory instability may be demonstrated by a significant number and severity of oxygen desaturations during sleep in the presence of OSA, with or without NH, and oxygen desaturations with central pauses at rest during wakefulness. Interestingly, during daily activities that require submaximal effort, children may not experience oxygen desaturations. Early recognition of respiratory abnormalities and targeted therapeutic interventions are important to limit associated morbidity and mortality in ROHHAD.

Obstructive sleep apnea in children aged 3 years and younger: Rate and risk factors.

OBJECTIVE: Undiagnosed and untreated obstructive sleep apnea (OSA) can predispose children to neurobehavioural consequences. However, there is a lack of data identifying rate of, and risk factors for, OSA in very young healthy children. The objective of this study was to determine the rate of OSA and identify risk factors associated with the presence and severity of OSA in children aged 3 years and younger. METHODS: This was a retrospective chart review of healthy children between 1 and 3 years old who had a baseline polysomnogram (PSG) between January 2012 and June 2017. Patient demographics, referral history, and PSG data were recorded. RESULTS: One hundred and thirteen children were referred for a PSG, of which 66 (58%) were diagnosed with OSA and 47 (42%) did not have OSA. In the OSA group, 13 (20%) were mild and 53 (80%) were moderate-severe. Nasal congestion (P=0.001), adenoid hypertrophy (P=<0.001), and tonsillar hypertrophy (P=0.04) reported at the time of referral were more common in the OSA group compared to the no-OSA group. Binary logistic regression analysis showed that referral from an otolaryngologist (odds ratio=2.6, 95% confidence interval=1.1 to 6.0) were associated with moderate-severe OSA. CONCLUSION: A high rate of OSA was found among children aged 3 years and younger. Children referred by an otolaryngologist are more likely to be diagnosed with moderate-severe OSA. Children aged 3 years and younger with symptoms of OSA should be considered high-risk for OSA and be prioritized for early PSG and management.

Positional obstructive sleep apnea in an obese pediatric population.

STUDY OBJECTIVES: Positional obstructive sleep apnea (POSA) is a phenotype of obstructive sleep apnea (OSA) where sleep-related obstructive events occur predominantly in the supine position. Limited knowledge exists regarding the presence of POSA in children with obesity. The study objective was to determine the prevalence of POSA while identifying factors associated with POSA in children with obesity. METHODS: This was a cross-sectional study of children with obesity, aged 8 to 18 years, with a diagnostic polysomnogram (PSG) between 2012 to 2019, who were referred for the evaluation of sleep-related breathing. POSA was defined as an overall obstructive apnea-hypopnea index (OAHI) ≥5 events/h and a supine OAHI to nonsupine OAHI ratio of ≥2. Patient demographics, anthropometrics, and PSG data were recorded. RESULTS: Of the 112 children with obesity with a diagnostic PSG, 43 (38%) had OSA. Among those with OSA, 25 of 43 (58%) had POSA (mean age: 14.6 ± 2.3 years; mean body mass index: 37.7 ± 7.6 kg/m²; 68% male) and 18 of 43 (42%) had non-POSA (mean age: 13.9 ± 2.8 years; mean body mass index: 37.9 ± 7.2 kg/m²; 78% male). Among those with POSA, 13 of 25 (52%) had mild OSA, 7 of 25 (28%) had moderate OSA, and 5 of 25 (20%) had severe OSA. No significant differences were found in age, sex, and anthropometric measures between POSA and non-POSA groups. Time spent in supine and nonsupine sleep did not differ significantly between groups. CONCLUSIONS: In children with obesity and OSA, POSA occurs frequently. Identifying POSA allows for potential targeted positional therapy for children with obesity.

Respiratory Dysfunction and Sleep-Disordered Breathing in Children With Myasthenia Gravis.

OBJECTIVES: The purpose of this study was to prospectively evaluate sleep patterns and the presence of sleep-disordered breathing in children with myasthenia gravis. We further aimed to examine the relationship between sleep and daytime respiratory function using spirometry tests including upright and supine forced vital capacity, sniff nasal inspiratory pressure, and maximal inspiratory pressure. METHODS: Eleven children between 3 and 18 years old with confirmed myasthenia gravis were recruited from The Hospital for Sick Children Neuromuscular Clinic in this prospective observational study. After informed consent was obtained, patients underwent a comprehensive clinical assessment with collection of anthropometric data. Following this, all subjects performed pulmonary function tests, overnight polysomnography and completed the Epworth Sleepiness Scale questionnaire. RESULTS: Two of eleven children who reported no symptoms of sleep disordered breathing were diagnosed with mild to moderate obstructive sleep apnea. Pulmonary function tests showed abnormal maximal inspiratory pressure in 6 of 11 patients, whereas seated forced vital capacity as well as seated to supine forced vital capacity ratios were normal in the entire group. CONCLUSIONS: In our small group of pediatric myasthenia gravis subjects, there was an unexpected finding of obstructive sleep apnea in 2 of the 11 patients studied. Maximal inspiratory pressure appears to be a more sensitive method of detecting abnormalities compared to upright or seated forced vital capacity. A larger multicenter study is needed to validate our findings and to determine the impact of obstructive sleep apnea in the pediatric myasthenia gravis population as well as risk factors associated with sleep disordered breathing.

Evaluating the effects of general anesthesia on sleep in children undergoing elective surgery: an observational case-control study.

Study Objectives: Previous research has suggested that general anesthetics can disturb postoperative sleep patterns by affecting the sleep-wake cycle. The objective was to identify the effects of general anesthetics on sleep quality and related behavioral changes in children. Methods: This was a prospective, observational case-control study with children, aged 18 months to 8 years, undergoing general anesthesia for elective surgery. Participants wore an actigraph for 7 days on three occasions: prior to surgery, the immediate postoperative period, and 3 months after surgery. Data regarding behavior patterns were collected using behavioral assessments at baseline, the first postoperative week, and 3 months following surgery. Results: Thirty-one participants (mean age 4.8 ± 2.0 years, 81% male) underwent urologic or otolaryngologic surgery. The median (interquartile range) anesthetic duration was 132.0 (80.0-184.0) min. No significant differences were found in sleep efficiency, total sleep time, wake time after sleep onset, or sleep onset latency between baseline, 7 day postoperative period, and the 3 month follow-up. No significant differences were found in sleep-related behavioral metrics including internalizing and externalizing behaviors, and executive functioning. Data were compared with a control group of 18 participants (mean age 5.3 ± 1.8 years, 61% male). No significant differences were found in sleep patterns and related behavioral metrics between both groups. Conclusions: In this study, general anesthesia did not result in disturbed sleep or associated negative behavioral changes in otherwise healthy children undergoing elective surgeries of low complexity. Physicians can advise parents that a child's surgery and associated general anesthetic exposure may not result in significant changes in postoperative sleep patterns.

Utility of brain MRI in children with sleep-disordered breathing.

OBJECTIVES/HYPOTHESIS: To investigate the utility of a brain magnetic resonance imaging (MRI) in children with sleep-disordered breathing (SDB), classified as isolated obstructive sleep apnea (OSA) in the absence of adenotonsillar hypertrophy, persistent OSA following adenotonsillectomy, isolated central sleep apnea (CSA) of unclear etiology, OSA with coexisting CSA of unclear etiology, or unexplained nocturnal hypoventilation (NH). STUDY DESIGN: Retrospective chart review of polysomnography (PSG) and brain MRI data. METHODS: Children with PSG evidence of SDB, as described above, and who subsequently had their first brain MRI, were included. PSG, MRI data, and subsequent interventions were recorded. RESULTS: A total of 59 of 6,087 (1%) children met inclusion criteria. Of those, 28 of 59 (47%) were nonsyndromic children and 31 of 59 (53%) were syndromic children with an underlying medical disorder. Abnormal brain MRI findings were observed in 19 of 59 (32%) children, where eight of 19 (42%) were nonsyndromic and 11 of 19 (58%) were syndromic. Abnormal brain MRI findings were most common in syndromic children with combined OSA and CSA without adenotonsillar hypertrophy. Isolated OSA was also a common PSG finding associated with an abnormal brain MRI. Of the nonsyndromic children with an abnormal brain MRI, the most common abnormal brain MRI finding was Chiari malformation (CM), observed in 88% of the group. A brainstem tumor was identified in one nonsyndromic child. Interventions following brain MRI included neurosurgery, chemotherapy, and noninvasive positive pressure ventilation (NiPPV). CONCLUSION: A brain MRI is an important diagnostic tool in syndromic and nonsyndromic children, especially in children with either isolated OSA or combined OSA and CSA without a clear etiology. LEVEL OF EVIDENCE: 4. Laryngoscope, 2016 127:513-519, 2017.