To aid in the diagnosis of Primary Ciliary Dyskinesia (PCD) and to evaluate the respiratory epithelium in respiratory disease, normal age-related reference ranges are needed for ciliary beat ...frequency (CBF), beat pattern and ultrastructure. Our aim was to establish reference ranges for healthy Chinese children.
Ciliated epithelial samples were obtained from 135 healthy Chinese children aged below 18 years by brushing the inferior nasal turbinate. CBF and beat pattern were analysed from high speed video recordings. Epithelial integrity and ciliary ultrastructure were assessed using transmission electronic microscopy.
The mean CBF from 135 children studied was 10.1 Hz (95% CI 9.8 to 10.4). Approximately 20% (ranged 18.0-24.2%) of ciliated epithelial edges were found to have areas of dyskinetically beating cilia. Normal beat pattern was observed in ciliated epithelium from all subjects. We did not find any effect of exposure to second hand smoke on CBF in our subjects. Microtubular defects were found in 9.3% of all of the cilia counted in these children, while other ciliary ultrastructural defects were found in less than 3%.
We established the reference range for CBF, beat pattern and ultrastructure in healthy Chinese children. Using similar methodology, we found a lower overall mean CBF than previously obtained European values. This study highlights the need to establish normative data for ciliary function in different populations.
Aim
To investigate the association between the risk of attention‐deficit/hyperactivity disorder (ADHD) and preterm birth and determine how postnatal complications in children born preterm is ...associated with the risk of ADHD.
Method
This population‐based cohort study used data from the Hong Kong electronic medical records. We followed 359 614 children (48% female; 6–17 years old, mean 11 years 7 months, SD 3 years 2 months) born in public hospitals in Hong Kong from 1st January 2004 to 31st December 2014 and collected medical records and demographic details for mothers and children until 11th November 2020.
Results
The risk of ADHD was 4.0% in children born at term and 5.1% in children born preterm. The odds ratio for ADHD was 2.08 (95% confidence interval CI 1.64–2.64) for children born extremely preterm, 1.64 (95% CI 1.46–1.85) for children born very preterm, and 1.15 (95% CI 1.08–1.23) for children born late preterm. Among preterm postnatal complications, only early respiratory disease, retinopathy of prematurity (ROP), and intraventricular haemorrhage were significant predictors of ADHD after controlling for preterm birth, other risk factors, and sociodemographic variables. The excess risk of ADHD among children born very preterm or late preterm could be partly explained by respiratory disease. ROP partially mediated the risk of ADHD in children born very preterm.
Interpretation
Children born preterm in all subcategories, from extremely preterm to late preterm, have increased risk of ADHD. Early respiratory infection partially mediates the risk of ADHD in children born preterm.
A test negative study was carried out from 13 June through to 15 November 2023 enrolling 3183 children hospitalized with acute respiratory illness in Hong Kong. Influenza A and B viruses were ...detected in 528 (16.6%) children, among which 419 (79.4%) were influenza A(H3N2). The overall vaccine effectiveness against hospitalization associated with any influenza virus infection was estimated as 22.4% (95% CI: −11.7%, 46.1%), and against influenza A(H3N2) specifically was 14.3% (95% CI: −29.2%, 43.2%). Despite the moderate to low VE estimated here, which could be a result of waning immunity and antigenic drift, influenza vaccination remains an important approach to reduce the impact of influenza in children.
Objectives To examine the average sleep duration in Chinese preschoolers and to investigate the association between sleep duration and school readiness. Study design This is a cross-sectional study ...that included 553 Chinese children (mean age = 5.46 years) from 20 preschools in 2 districts of Hong Kong. Average daily sleep duration in the last week was reported by parents and school readiness as measured by the teacher-rated Chinese Early Development Instrument (CEDI). Results Most Chinese preschoolers had 9-10 hours of sleep per day. Only 11% of preschoolers had the recommended 11-12 hours of sleep per day. This group was associated with more “very ready” CEDI domains. Sleep deprivation (≤7 hours per day) was associated with a lower CEDI total score, lower scores in the emotional maturity and language/cognitive domain, and prosocial behaviors subdomain but a greater score in the hyperactivity/inattention subdomain. Children with a lower family socioeconomic index, lower maternal education level, infrequent parent-child interactions, and who used electronic devices for more than 3 hours per day had shortened sleep durations. Conclusions Optimal sleep duration was associated with better school readiness in preschool children, whereas sleep deprivation was associated with lower school readiness, more hyperactivity and inattention, and less prosocial behavior.
The prevalence of allergic diseases has been increasing in developing areas but has reached a plateau in many developed areas. Regular surveys are imperative to assess the disease burden for the ...prioritization of resource allocation.
We examined the change in the prevalence of wheezing, allergic rhinitis (AR), and eczema in school-aged children with possible associative factors and possible health effects of school air quality.
This was the third repeated cross-sectional study conducted in 2015-2016 using the International Study of Asthma and Allergies in Childhood (ISAAC) protocol. Our first and second surveys were conducted in 1994-1995 and 2000-2001, respectively. Regarding the third survey, we recruited 3698 children aged 6-7 from 33 local schools in 18 districts. Air quality, temperature, and humidity were also measured. The changes in prevalence, multiple regression, and GLIMMIX procedure were analyzed.
From our first survey to our third survey, the increased prevalences for lifetime wheeze, current wheeze, lifetime rhinitis, current rhinitis, current rhinoconjunctivitis, lifetime chronic rash, and current chronic rash were 4.2%, 2.1%, 12.5%, 12.6%, 14.2%, 3.9%, and 4.1%, respectively. Increased prevalence of parental atopy had the strongest association with an increased prevalence of each of these seven health outcomes. There was no significant association between school air pollutant levels and the prevalence of health outcomes.
There was an increase in the prevalence of wheezing, allergic rhinitis, and eczema across the surveys. The most important associated risk factor identified was the increased prevalence of a parental history of atopy.
Biliary atresia (BA) is the most common obstructive cholangiopathy in neonates, often progressing to end-stage cirrhosis. BA pathogenesis is believed to be multifactorial, but the genetic ...contribution, especially for nonsyndromic BA (common form: > 85%) remains poorly defined.
We conducted whole exome sequencing on 89 nonsyndromic BA trios to identify rare variants contributing to BA etiology. Functional evaluation using patients’ liver biopsies, human cell and zebrafish models were performed. Clinical impact on respiratory system was assessed with clinical evaluation, nasal nitric oxide (nNO), high speed video analysis and transmission electron microscopy.
We detected rare, deleterious de novo or biallelic variants in liver-expressed ciliary genes in 31.5% (28/89) of the BA patients. Burden test revealed 2.6-fold (odds ratio (OR) 95% confidence intervals (CI)= 2.58 1.15–6.07, adjusted p = 0.034) over-representation of rare, deleterious mutations in liver-expressed ciliary gene set in patients compared to controls. Functional analyses further demonstrated absence of cilia in the BA livers with KIF3B and TTC17 mutations, and knockdown of PCNT, KIF3B and TTC17 in human control fibroblasts and cholangiocytes resulted in reduced number of cilia. Additionally, CRISPR/Cas9-engineered zebrafish knockouts of KIF3B, PCNT and TTC17 displayed reduced biliary flow. Abnormally low level of nNO was detected in 80% (8/10) of BA patients carrying deleterious ciliary mutations, implicating the intrinsic ciliary defects.
Our findings support strong genetic susceptibility for nonsyndromic BA. Ciliary gene mutations leading to cholangiocyte cilia malformation and dysfunction could be a key biological mechanism in BA pathogenesis.
The study is supported by General Research Fund, HMRF Commissioned Paediatric Research at HKCH and Li Ka Shing Faculty of Medicine Enhanced New Staff Start-up Fund.
Bronchiectasis is the abnormal dilation of the airway which may be caused by various etiologies in children. Beyond the more recognized cause of bacterial and viral infections and primary ...immunodeficiencies, other genetic conditions such as cystic fibrosis and primary ciliary dyskinesia (PCD) can also contribute to the disease. Currently, there is still debate on whether genome sequencing (GS) or exome sequencing reanalysis (rES) would be beneficial if the initial targeted testing results returned negative. This study aims to provide a back-to-back comparison between rES and GS to explore the best integrated approach for the functional and genetics evaluation for patients referred for assessment of bronchiectasis. In phase 1, an initial 60 patients were analyzed by exome sequencing (ES) with one additional individual recruited later as an affected sibling for ES. Functional evaluation of the nasal nitric oxide test, transmission electron microscopy, and high-speed video microscopy were also conducted when possible. In phase 2, GS was performed on 30 selected cases with trio samples available. To provide a back-to-back comparison, two teams of genome analysts were alternatively allocated to GS or rES and were blinded to each other's analysis. The time for bioinformatics, analysis, and diagnostic utility was recorded for evaluation. ES revealed five positive diagnoses (5/60, 8.3%) in phase 1, and four additional diagnoses were made by rES and GS (4/30, 13%) during phase 2. Subsequently, one additional positive diagnosis was identified in a sibling by ES and an overall diagnostic yield of 10/61 (16.4%) was reached. Among those patients with a clinical suspicion of PCD (n = 31/61), the diagnostic yield was 26% (
= 8/31). While GS did not increase the diagnostic yield, we showed that a variant of uncertain significance could only be detected by GS due to improved coverage over ES and hence is a potential benefit for GS in the future. We show that genetic testing is an essential component for the diagnosis of early-onset bronchiectasis and is most effective when used in combination with functional tools such as TEM or HSVM. Our comparison of rES vs. GS suggests that rES and GS are comparable in clinical diagnosis.
Sleep problems are common in children with autism spectrum disorder. Although the effects of parent-based sleep intervention were shown to be promising, previous research was limited to the ...face-to-face service model, which might limit accessibility. This study examined a sleep-focused parent training group delivered via telehealth for treating insomnia in preschool children with autism spectrum disorder, which allowed parents to join the intervention remotely. Results showed that children in the intervention group had greater improvements in sleep and insomnia symptoms after treatment, as compared to those who only received care as usual. This sleep-focused treatment also led to improved daytime behaviors, especially externalizing problems such as hyperactivity and conduct problems, in children with autism spectrum disorder. Parents who had attended the training also reported reduced parental stress level after treatment. The findings supported the feasibility and promising effects of a brief parent-based sleep intervention delivered via telehealth for preschooler with autism spectrum disorder.
A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong. We examined the effect of these interventions and ...behavioural changes of the public on the incidence of COVID-19, as well as on influenza virus infections, which might share some aspects of transmission dynamics with COVID-19.
We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (Rt) for COVID-19 and influenza A H1N1 to estimate changes in transmissibility over time. Attitudes towards COVID-19 and changes in population behaviours were reviewed through three telephone surveys done on Jan 20–23, Feb 11–14, and March 10–13, 2020.
COVID-19 transmissibility measured by Rt has remained at approximately 1 for 8 weeks in Hong Kong. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% CI 34–53%) reduction in transmissibility in the community, from an estimated Rt of 1·28 (95% CI 1·26–1·30) before the start of the school closures to 0·72 (0·70–0·74) during the closure weeks. Similarly, a 33% (24–43%) reduction in transmissibility was seen based on paediatric hospitalisation rates, from an Rt of 1·10 (1·06–1·12) before the start of the school closures to 0·73 (0·68–0·77) after school closures. Among respondents to the surveys, 74·5%, 97·5%, and 98·8% reported wearing masks when going out, and 61·3%, 90·2%, and 85·1% reported avoiding crowded places in surveys 1 (n=1008), 2 (n=1000), and 3 (n=1005), respectively.
Our study shows that non-pharmaceutical interventions (including border restrictions, quarantine and isolation, distancing, and changes in population behaviour) were associated with reduced transmission of COVID-19 in Hong Kong, and are also likely to have substantially reduced influenza transmission in early February, 2020.
Health and Medical Research Fund, Hong Kong.
Summary
Objective
Early onset drug‐resistant epilepsy is a neurologic disorder in which 2 antiepileptic drugs fail to maintain the seizure‐free status of the patient. Heterogeneous clinical ...presentations make the diagnosis challenging. We aim to identify the underlying genetic causes of a pediatric cohort with drug‐resistant epilepsy and evaluate whether the findings can provide information on patient management.
Methods
We include patients with drug‐resistant epilepsy onset before 18 years of age. Singleton clinical chromosomal microarray (CMA) followed by whole exome sequencing (WES) was performed using genomic DNA. In the first‐tier analysis of the exome data, we aimed to identify disease‐causing mutations in 546 genes known to cause, or to be associated with, epilepsy. For negative cases, we proceeded to exome‐wide analysis. Rare coding variants were interrogated for pathogenicity based on the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results
We recruited 50 patients. We identified 6 pathogenic or likely pathogenic mutations, giving a diagnostic yield of 12%. Mutations were found in 6 different genes: SCN8A, SCN1A, MECP2, CDKL5, DEPDC5, and CHD2. The CDKL5 variant was found to be mosaic. One variant of unknown significance (VUS) in KCNT1 was found in a patient with compatible clinical features. Of note, a reported pathogenic SCN5A mutation known to contribute to Brugada syndrome, was also found in the patient with an SCN1A mutation.
Significance
Our study suggests that singleton WES is an effective diagnostic tool for drug‐resistant epilepsy. Genetic diagnosis can help to consolidate the clinical diagnosis, to facilitate phenotypic expansion, and to influence treatment and management options for seizure control in our patients. In our study, a significant portion of the genetic findings are known to be associated with an increased risk of sudden unexpected death in epilepsy (SUDEP). These findings could assist with more appropriate management in patients with epilepsy.
PDF
