Sleep disturbances in children and adolescents after kidney transplantation.

BACKGROUND: Disturbances of sleep are prevalent among children with chronic kidney disease. However, the aetiology of sleep disorders in children particularly after kidney transplantation is not clear. We sought to ascertain the prevalence and type of sleep disturbances in paediatric kidney transplant recipients and to identify predictors of sleep disturbances in this population. METHODS: Caregivers of kidney transplant recipients completed online questionnaires about their child's sleep. The questionnaires utilised were the Sleep Disturbance Scale for Children (SDSC), the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), questions about sleep hygiene, and questions about restless leg syndrome. Demographic and clinical details were collected from medical records. RESULTS: Thirty-five children were included in the study, with a median (IQR) age of 14.1 years (9.5-16.1) and median years (IQR) since transplant of 3.7 (0.7-8.7) years, and 72.0% were identified to have at least one category of sleep disturbance according to scores on the SDSC. The most common sleep disturbances reported were disorders of initiating and maintaining sleep (DIMS) (40.0%) and disorders of excessive somnolence (DOES) (31.4%). Statistically significant predictors of sleep disturbances include low estimated glomerular filtration rate and increased age. Among children who screened positive for DIMS and DOES, the majority indicated use of electronic devices in 1 h before bed. CONCLUSIONS: A high prevalence of sleep disturbances has been identified in children after kidney transplants, and some risk factors may be modifiable. Further studies are required to understand whether there are other readily modifiable predictors of sleep disturbances.

Quantitative assessment of nocturnal neural respiratory drive in children with and without obstructive sleep apnoea using surface EMG.

NEW FINDINGS: What is the central question of this study? Recent studies have suggested potential utility of non-normalized respiratory muscle EMG as an index of neural respiratory drive (NRD). Whether NRD measured using non-normalized surface EMG of the lateral chest wall overlying the diaphragm (sEMGcw) recorded during nocturnal clinical polysomnography can differentiate children with and without obstructive sleep apnoea (OSA) is not known. What is the main finding and its importance? Non-normalized sEMGcw was increased in children with OSA and an additional group of snoring children without OSA but subjectively increased respiratory effort compared with primary snorers. The sEMGcw has potential clinical utility in evaluation of children with sleep-disordered breathing as an objective, non-invasive, non-volitional marker of NRD. ABSTRACT: Our aim was to investigate whether neural respiratory drive measured by non-normalized surface EMG recorded from the chest wall overlying the diaphragm (sEMGcw) differentiates children with and without obstructive sleep apnoea (OSA). Polysomnography data of children aged 0-18 years were divided into the following three groups: (i) primary snorers (PS); (ii) snoring children without OSA but with increased work of breathing (incWOB; subjective physician report of increased respiratory effort during sleep); and (iii) children with OSA [obstructive apnoea-hypopnoea index (OAHI) >1 h-1 ]. Excerpts of sEMGcw obtained during tidal unobstructed breathing from light, deep and rapid eye movement sleep were exported for quantitative analysis. Overnight polysomnography data from 45 PS [median age 4.4 years (interquartile range 3.0-7.7 years), OAHI 0 h-1 (0.0-0.2 h-1 )], 19 children with incWOB [age 2.8 years (2.4-5.7 years), OAHI 0.1 h-1 (0.0-0.4 h-1 )] and 27 children with OSA [age 3.6 years (2.6-6.2 years), OAHI 3.7 h-1 (2.3-6.9 h-1 )] were analysed. The sEMGcw was higher in those with OSA [8.47 µV (5.98-13.07 µV); P < 0.0001] and incWOB [8.97 µV (5.94-13.43 µV); P < 0.001] compared with PS [4.633 µV (2.98-6.76 µV)]. There was no significant difference in the sEMGcw between children with incWOB and OSA (P = 0.78). Log sEMGcw remained greater in children with OSA and incWOB compared with PS after age, body mass index centiles, sleep stages and sleep positions were included in the mixed linear models (P < 0.0001). The correlation between sEMGcw and OAHI in children without OSA was small (rs  = 0.254, P = 0.04). The sEMGcw is increased in children with OSA and incWOB compared with PS.

Clinical outcomes of adults and children with cystic fibrosis during the COVID-19 pandemic.

BACKGROUND: The onset of the COVID-19 pandemic was associated with restricted community movement and limited access to healthcare facilities, resulting in changed clinical service delivery to people with cystic fibrosis (CF). This study aimed to determine clinical outcomes of Australian adults and children with CF in the 12-months following the onset of the COVID-19 pandemic. METHODS: This longitudinal cohort study used national registry data. Primary outcomes were 12-month change in percent predicted forced expiratory volume in one second (FEV1 %pred), body mass index (BMI) in adults and BMI z-scores in children. A piecewise linear mixed-effects model was used to determine trends in outcomes before and after pandemic onset. RESULTS: Data were available for 3662 individuals (median age 19.6 years, range 0-82). When trends in outcomes before and after pandemic onset were compared; FEV1 %pred went from a mean annual decline of -0.13% (95%CI -0.36 to 0.11) to a mean improvement of 1.76% (95%CI 1.46-2.05). Annual trend in BMI improved from 0.03 kg/m2 (95%CI -0.02-0.08) to 0.30 kg/m2 (95%CI 0.25-0.45) and BMI z-scores improved from 0.05 (95%CI 0.03-0.07) to 0.12 (95%CI 0.09-0.14). Number of hospitalisations decreased from a total of 2656 to 1957 (p < 0.01). Virtual consultations increased from 8% to 47% and average number of consultations per patient increased from median (IQR) of 4(2-5) to 5(3-6) (p < 0.01). CONCLUSION: In the 12-months following the onset of the COVID-19 pandemic, there was an improvement in the clinical outcomes of people with CF when compared to the pre-pandemic period.

Diet and the gut-lung axis in cystic fibrosis - direct & indirect links.

Cystic fibrosis (CF) is a multisystem, autosomal, recessive disease primarily affecting the lungs, pancreas, gastrointestinal tract, and liver. Whilst there is increasing evidence of a microbial 'gut-lung axis' in chronic respiratory conditions, there has been limited analysis of such a concept in CF. We performed a comprehensive dietary and microbiota analysis to explore the interactions between diet, gastrointestinal microbiota, respiratory microbiota, and clinical outcomes in children with CF. Our results demonstrate significant alterations in intestinal inflammation and respiratory and gastrointestinal microbiota when compared to age and gender matched children without CF. We identified correlations between the gastrointestinal and respiratory microbiota, lung function, CF pulmonary exacerbations and anthropometrics, supporting the concept of an altered gut-lung axis in children with CF. We also identified significant differences in dietary quality with CF children consuming greater relative proportions of total, saturated and trans fats, and less relative proportions of carbohydrates, wholegrains, fiber, insoluble fiber, starch, and resistant starch. Our findings position the CF diet as a potential modulator in gastrointestinal inflammation and the proposed gut-lung axial relationship in CF. The dietary intake of wholegrains, fiber and resistant starch may be protective against intestinal inflammation and should be explored as potential therapeutic adjuvants for children with CF.

Dual CFTR modulator therapy efficacy in the real world: lessons for the future.

Stringent analyses caution against drawing conclusions about the real-world efficacy of CFTR modulator therapy too early https://bit.ly/3dJt6no.

Telehealth application of an ultrasonic home spirometer.

OBJECTIVE: To investigate the validity and home use of a personal ultrasonic spirometer. METHODS: Supervised spirometry was performed using laboratory equipment and a personal ultrasonic spirometer. In addition, the ability of children to perform acceptable spirometry during supervised telehealth appointments at home was assessed. RESULTS: 59 children completed spirometry on both devices. There was high between-device intraclass correlation coefficient (ICC) for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC): ICC 0.991 (95% CI 0.985 to 0.995) and 0.989 (95% CI 0.981 to 0.993), respectively. Bland-Altman analysis revealed mean bias and limits of agreement of -0.01 (-0.22 to 0.24) L for FEV1 and -0.02 (-0.30 to 0.33) L for FVC. 125 of 140 (89%) supervised telehealth spirometry sessions were acceptable. CONCLUSION: There was excellent reliability in between-device measurements; however, the limits of agreement were wide. Therefore, caution is needed if the device is used interchangeably with laboratory equipment. High success rates of telehealth spirometry sessions indicate the device is suitable for this application.

Daytime predictors of nocturnal hypercapnic hypoventilation in children with neuromuscular disorders.

OBJECTIVES: To examine objective daytime predictors of nocturnal hypercapnic hypoventilation (NHH) and identify a forced vital capacity (FVC) z-score cut off that predicts NHH using the 2012 Global Lung Function Initiative (GLI) reference equations in pediatric neuromuscular patients. DESIGN: Single-centre retrospective medical record review. SETTING: Tertiary pediatric hospital in Australia. PATIENTS: Children (<18 years old) with a neuromuscular disorder (NMD) who had a diagnostic sleep study over a 5-year period. RESULTS: Fifty children were included, median age 11.9 years (interquartile range [IQR]: 4.5-14.3). The majority of children had a diagnosis of Duchenne Muscular Dystrophy (32%). NHH was diagnosed in 18 children (36%). Multivariate logistic regression analysis performed for the entire cohort confirmed a statistically significant association between NHH and scoliosis (odds ratio [OR]: 3.3, p = 0.03), but not age (OR: 1.01, p = 0.26), body mass index z-score (OR: 0.86, p = 0.26) or use of a wheelchair for mobility (OR: 1.25, p = 0.72). For the subset of 29 children who had spirometry testing (median age 12.9 years [IQR: 10.2-14.3]), FVC z-score was the only statistically significant predictor of NHH (OR: 0.45, p = 0.02). NHH was predicted by an FVC z-score <-3.24 (sensitivity 78%, specificity 73%), or FVC <60% predicted (sensitivity 78%, specificity 73%). There was a strong positive correlation between FVC and forced expiratory volume in 1 s z-scores (rp = 0.98, p = 0.00) and FVC and peak expiratory flow  z-scores (rp = 0.72, p = 0.00). CONCLUSION: Children with a NMD and scoliosis or a lower FVC z-score have increased odds of having NHH.

Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research programme: a protocol for prospective, longitudinal, controlled, observational studies in children with chronic disease at an Australian tertiary paediatric hospital.

INTRODUCTION: Chronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the 'Evaluating the Alimentary and Respiratory Tracts in Health and disease' (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions. METHODS AND ANALYSIS: The EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of individual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts.Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor. ETHICS AND DISSEMINATION: Ethics approval: Sydney Children's Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04071314.

Age-related levels of fecal M2-pyruvate kinase in children with cystic fibrosis and healthy children 0 to 10years old.

BACKGROUND: The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract. METHODS: M2-PK was measured in stools collected from patients with CF and HC (0-10years). Linear mixed model analysis was used. RESULTS: M2-PK levels did not significantly change in children with CF (36 patients, 77 samples) (P=0.998) or HC (45 patients, 45 samples) (P=0.21), over the age range 0-10years. Patients with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7-28.6; 1.0-239.1] (n=77) vs. 1.0 [1.0-1.0; 1.0-50.0] (n=45) U/mL, respectively; P=0.001). CONCLUSIONS: Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life.

Validation of a quantitative method to measure neural respiratory drive in children during sleep.

AIMS: Quantitatively measure and validate analysis of neural respiratory drive (NRD) using a commercial polysomnography system in children during sleep. METHOD: Surface electromyogram of the diaphragm (sEMGdi) recorded from primary snoring children were analysed. A subset was re-analysed to assess intra- and inter-investigator reproducibility. Effects of different band pass filter settings (20-100Hz vs 10-1000Hz) on sEMGdi amplitude were evaluated. RESULTS: Mean sEMGdi from 45 children aged 4.38 years (median; IQR 3.00-7.96) was 5.05µV (SD 2.73). The sEMGdi had a high intra-subject intraclass correlation coefficient (ICC) of 0.88. sEMGdi analysis was reproducible with high ICC between occasions (0.99; 95% CI 0.98-0.99) and between investigators (0.98; 95% CI 0.97-0.99). There was also a high ICC (0.99, 95% CI 0.96-1.00) between the sEMGdi measured using different band-pass filter settings. Age and BMI were negative predictors of sEMGdi (p<0.0001 and p=0.0004 respectively). CONCLUSION: NRD in children during sleep as assessed by sEMGdi can be quantified in a reliable and reproducible fashion.

Annual Review Clinic improves care in children with cystic fibrosis.

BACKGROUND: It is unclear whether annual multidisciplinary reviews in cystic fibrosis (CF) patients should be conducted in dedicated annual review (AR) clinics or during continuous assessments throughout the year. Our aim was to assess the effect of introducing an AR clinic. METHODS: A retrospective written and electronic record review of CF patients was carried out for 2007 (no AR Clinic) and 2010 (established AR Clinic) calendar years. An internet-based satisfaction survey was distributed to families attending the AR clinic. RESULTS: In total, 123 children (mean age 9.5 years, range 1.32-18.8 years) and 141 children (8.3 years, 1.1-18.3 years) were included in 2007 and 2010 respectively. There was a significant increase in multidisciplinary reviews (documented annual review 28% vs 85%, P < 0.001; dietary assessment 46% vs 92%, P < 0.001) and investigations (OGTT 2% vs 74%, P < 0.001; abdominal ultrasound 35% vs 85%, P < 0.001) conducted after the introduction of AR clinic. The majority of the families surveyed (85%) were satisfied or very satisfied with the AR clinic. CONCLUSIONS: CF AR clinic significantly improves the number of annual investigations and multidisciplinary reviews performed. Families were satisfied with this new process.

Cost considerations of therapeutic options for children with asthma.

Asthma is a prevalent health condition in children, with economic implications for the individual and their family, as well as for societies with nationalized healthcare. Pharmaceutical cost is the main driver of healthcare expenditure in asthma. Existent explicit guidelines are meant to guide asthma management across all age groups, but they are failing. Pharmacologic management of asthma consists of a stepwise treatment approach to achieve symptom control. Various studies suggest a significant number of medical practitioners are prescribing inhaled corticosteroids (ICS) and ICS/long-acting beta agonist (LABA) combination inhalers inappropriately, including prescribing high doses of ICS without specialist consultation. ICS/LABA combination inhalers should only be used in persistent asthmatics, which account for approximately 5% of all children with asthma. Despite this, there is an increase in prescribing rates of ICS/LABA combination inhalers in the context of a decrease in the prevalence of asthma. Furthermore, there is inappropriate prescribing of ICS/LABA combination inhalers in children under 5 years of age, and initiation of relatively more expensive ICS/LABA combination inhalers in patients who have not previously been prescribed ICS. There is evidence to suggest that cost is a significant barrier to asthma management, especially for the more expensive ICS/LABA combination inhalers. Hence, prescribing cost-effective asthma medications appropriately is one of the most important strategies in reducing the morbidity and mortality associated with asthma. It is incumbent on every medical practitioner to not prescribe expensive medications if not indicated, both for the sake of the patient and for society.