A case-control study to investigate the prevalence of obstructive sleep apnea and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in children and young people with epilepsy.

STUDY OBJECTIVES: Epilepsy and obstructive sleep apnea syndrome (OSAS) are each relatively common in children. OSAS may affect cognition, such that recognition of OSAS is important for children and young people with epilepsy (CYPWE). Published pilot data reported 55% of CYPWE had symptoms suggestive of OSAS, compared with 7% of typically developing controls. The primary aim of this study was to ascertain OSAS prevalence by polysomnography in CYPWE, with secondary aims being to evaluate the utility of sleep questionnaires in CYPWE. METHODS: CYPWE and age- and sex-matched typically developing controls were studied. A single night of level I attended polysomnography was undertaken, along with questionnaires (Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire, Pittsburgh Sleep Quality Index, and the childhood and adolescent Epworth Sleepiness Scale). OSAS was defined as obstructive apnea-hypopnea index of ≥ 1 event/h. RESULTS: Polysomnography was performed in 72 children including 48 CYPWE (60% male) and 24 controls (54% male). Mean age (11 years) was similar for CYPWE and controls (P = .42), with slightly higher body mass index z scores (0.7 vs 0.1, P = .03) noted in CYPWE. Mean obstructive apnea-hypopnea index was 0.61 in CYPWE vs 0.42 in controls (P = .62). Despite higher Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire scores in CYPWE (0.38 vs 0.12, P < .001), no difference in OSAS prevalence (10% vs 4%, P = .78) was found. CYPWE had higher childhood and adolescent Epworth Sleepiness Scale (6 vs 3.5, P = .01) and Pittsburgh Sleep Quality Index (5 vs 3.3, P = .02) scores, indicating greater levels of daytime sleepiness and poorer sleep quality. CONCLUSIONS: The study found no evidence for increased OSAS prevalence in CYPWE, and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in predicting OSAS appears limited for CYPWE. CYPWE are, however, demonstrably sleepier and have poorer sleep quality. The cause for these findings remains unclear. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Investigation of Sleep Quality and Prevalence of Sleep-disordered Breathing in Children and Young People With Epilepsy; URL: https://www.clinicaltrials.gov/study/NCT03103841; Identifier: NCT03103841. CITATION: Urquhart DS, McLellan AE, Hill LE, et al. A case-control study to investigate the prevalence of obstructive sleep apnea and the utility of the Sleep-Related Breathing Disorder scale of the Pediatric Sleep Questionnaire in children and young people with epilepsy. J Clin Sleep Med. 2024;20(7):1039-1047.

Epidemiology of Robin sequence in the UK and Ireland: an active surveillance study.

BACKGROUND: Birth prevalence of Robin sequence (RS) is commonly reported as 1 case per 8000-14 000 live births. These estimates are based on single-source case ascertainment and may miss infants who did not require hospital admission or those without overt upper airway obstruction at birth. OBJECTIVES: To identify the true birth prevalence of RS with cleft palate in the UK and Ireland from a population-based birth cohort with high case ascertainment. METHODS: Active surveillance of RS with cleft palate was carried out in the UK/Ireland using dual sources of case ascertainment: British Paediatric Surveillance Unit (BPSU) reporting card and nationally commissioned cleft services. Clinical data were collected from notifying clinicians at two time points. RESULTS: 173 live-born infants met the surveillance case definition, giving a birth prevalence of 1 case per 5250 live births (19.1 per 100 000 (95% CI 16.2 to 21.9)), and 1:2690 in Scotland. 47% had non-isolated RS, with Stickler syndrome the most common genetic diagnosis (12% RS cases). Birth prevalence derived from the combined data sources was significantly higher than from BPSU surveillance alone. CONCLUSIONS: Birth prevalence of RS in the UK/Ireland derived from active surveillance is higher than reported by epidemiological studies from several other countries, and from UK-based anomaly registries, but consistent with published retrospective data from Scotland. Dual case ascertainment sources enabled identification of cases with mild or late-onset airway obstruction that were managed without hospital admission. Studies of aetiology and equivalent well-designed epidemiological studies from other populations are needed to investigate the identified geographical variability in birth prevalence.

Indirect effects of the COVID-19 pandemic on paediatric healthcare use and severe disease: a retrospective national cohort study.

OBJECTIVES: To determine the indirect consequences of the COVID-19 pandemic on paediatric healthcare utilisation and severe disease at a national level following lockdown on 23 March 2020. DESIGN: National retrospective cohort study. SETTING: Emergency childhood primary and secondary care providers across Scotland; two national paediatric intensive care units (PICUs); statutory death records. PARTICIPANTS: 273 455 unscheduled primary care attendances; 462 437 emergency department attendances; 54 076 emergency hospital admissions; 413 PICU unplanned emergency admissions requiring invasive mechanical ventilation; and 415 deaths during the lockdown study period and equivalent dates in previous years. MAIN OUTCOME MEASURES: Rates of emergency care consultations, attendances and admissions; clinical severity scores on presentation to PICU; rates and causes of childhood death. For all data sets, rates during the lockdown period were compared with mean or aggregated rates for the equivalent dates in 2016-2019. RESULTS: The rates of emergency presentations to primary and secondary care fell during lockdown in comparison to previous years. Emergency PICU admissions for children requiring invasive mechanical ventilation also fell as a proportion of cases for the entire population, with an OR of 0.52 for likelihood of admission during lockdown (95% CI 0.37 to 0.73), compared with the equivalent period in previous years. Clinical severity scores did not suggest children were presenting with more advanced disease. The greatest reduction in PICU admissions was for diseases of the respiratory system; those for injury, poisoning or other external causes were equivalent to previous years. Mortality during lockdown did not change significantly compared with 2016-2019. CONCLUSIONS: National lockdown led to a reduction in paediatric emergency care utilisation, without associated evidence of severe harm.

Airway clearance physiotherapy improves ventilatory dynamics during exercise in patients with cystic fibrosis: a pilot study.

BACKGROUND: Airflow limitation and dynamic hyperinflation may limit exercise capacity in patients with cystic fibrosis (CF). The aim was to investigate whether the undertaking of airway clearance physiotherapy (ACT) prior to cardiopulmonary exercise testing (CPET) results in improvements in exercise capacity. METHODS: A prospective randomised, cross-over pilot study was performed in children aged >9 years. Spirometry, plethysmography and CPET were performed on two separate occasions-one test with ACT prior to CPET and the other without. RESULTS: 12 patients with CF were included in the study with a mean (SD) age of 12.83 (1.85) years. No significant difference in peak oxygen uptake (VO2) was found between the tests. However, lower minute ventilation (VE) and ventilatory equivalents (VEVO2 and VEVCO2) at ventilatory threshold (VT) were noted when ACT was undertaken prior to CPET. The mean(SD) VE (L/min) at VT was 26.67 (5.49) vs 28.92 (6.3) (p=0.05), VEVO2 (L/min) at VT was 24.5 (1.75) vs 26.05 (2.5) (p=0.03) and VEVCO2 (L/min) at VT was 26.58 (2.41) vs 27.98 (2.11) (p=0.03). CONCLUSIONS: These pilot data suggest that ACT prior to exercise may lead to improved ventilatory dynamics during exercise in individuals with CF.

A Case of "Abnormally Abnormal" Hypoxic Ventilatory Responses: A Novel NPARM PHOX 2B Gene Mutation.

ABSTRACT: Congenital central hypoventilation syndrome (CCHS) is a rare disorder associated with dysregulation of the autonomic ventilatory response to hypoxia and hypercarbia usually caused by polyalanine repeat expansion mutations in the PHOX 2B gene. Non-polyalanine repeat mutations (NPARM) represent approximately 10% of cases, and usually require continuous ventilation during sleep, although our knowledge of disease progression is limited. Here we present a case with a novel NPARM CCHS mutation associated with a premature stop codon for the PHOX 2B protein. Despite the type of the mutation, patient management with supplementary oxygen has been sufficient. Experience from our case may help when counseling parents.

Modifier effect of the Toll-like receptor 4 D299G polymorphism in children with cystic fibrosis.

INTRODUCTION: Clinical phenotype varies amongst cystic fibrosis (CF) patients with identical CF transmembrane regulator (CFTR) genotype, suggesting genetic modifiers exist. One potential modifier is the Toll-like receptor 4 (TLR4) gene. TLR4 binds lipopolysaccharide (LPS), a constituent of Pseudomonas aeruginosa (PA), activating innate immunity and promoting inflammation. TLR4 polymorphisms are associated with LPS-hyporesponsiveness and may be protective in CF due to decreased inflammation. MATERIALS AND METHODS: DNA was extracted from blood of recruited CF subjects, and PCR performed to establish TLR4 D299G genotype. Case-notes were reviewed to obtain clinical data. Subjects possessing the TLR4 299G allele were compared with age, sex, and CFTR genotype-matched wild-type (299DD) subjects and also with all controls. RESULTS: 100 subjects (mean age 8.9 years) were studied, with 11 299DG heterozygotes identified. On case-matched analyses, no statistically significant differences between groups were found for mean +/- SEM rates of change of %predicted FEV(1)/year (0.9 +/- 2.3 (DD) vs. - 3.9 +/- 2.8 (DG), p = 0.22), %predicted FEV(1) (76 +/- 8 vs. 74 +/- 11), p = 0.91), or z scores for height ( - 0.47 +/- 0.26 vs. - 0.24 +/- 0.19, p = 0.48) and weight ( - 0.01 +/- 0.22 vs. - 0.29 +/- 0.27, p = 0.44). Median +/- SE survival age at first PA isolation was also not significantly different (3.5 +/- 2.1 vs. 6.5 +/- 2.4 years, p = 0.29). No statistically significant differences were noted when 299DG heterozygotes were compared with all controls. CONCLUSIONS: Potential reasons for absence of modifier effect include the basolateral location of TLR4 receptors on respiratory epithelium, or because inflammatory response to PA in the CF airway is so overwhelming that even a blunted response (as suggested for the 299G allele) results in increased inflammation and lung damage.

Deaths in childhood from cystic fibrosis: 10-year analysis from two London specialist centres.

INTRODUCTION: Death in childhood from cystic fibrosis (CF) is now an uncommon event in the U.K. We wished to assess the circumstances surrounding deaths (and lung transplantation) in the modern era of CF care. METHODS: A retrospective review was carried out pooling data from two large paediatric specialist CF units in London for the 10-year period 2000-2009 inclusive. RESULTS: There were 11 deaths and eight children who had a lung transplant out of 1022 children cared for in this period. Median age of death was 14.2 years and transplant 13.0 years, with a female preponderance (82% deaths and 75% transplants). Apart from one child (forced expiratory volume in 1 s (FEV1) 69%), lung function indicated severe lung disease (median FEV1 33%, range 12%-69%). Values 5 years prior to death were not predictive (median FEV1 62%, range 32%-96%), and those 1 year prior were similar to the last recorded levels. Almost all (10/11) died in hospital and 5/11 (45%) were ventilated. Respiratory failure was the commonest mode of death (64%). Only four children (36%) were receiving palliative care, and in six cases (55%) care was withdrawn. CONCLUSIONS: The number of deaths in children with CF was small but often unpredictable, so active management was continued until late in the majority, reflected by the fact that almost all were in hospital, and more than half were ventilated. If death from respiratory failure is anticipated following a steady decline, palliative care should be instituted well in advance, with attention to appropriate end of life care.