Sl Lee

Increasing prevalence of allergic rhinitis but not asthma among children in Hong Kong from 1995 to 2001 (Phase 3 International Study of Asthma and Allergies in Childhood).

There is a worldwide belief that the prevalence of asthma and other allergic diseases is increasing but the measures used in many studies are susceptible to systematic errors. We examined the trend of asthma, allergic rhinitis and eczema prevalence in school children aged 6–7 years in Hong Kong from 1995 to 2001 using standardized ISAAC methodology. There were 4448 and 3618 children participating in 2001 and 1995, respectively. The prevalence of life‐time rhinitis (42.4% vs. 38.9%, p < 0.01), current rhinitis (37.4% vs. 35.1%, p < 0.03), current rhinoconjunctivitis (17.2 vs. 13.6%, p < 0.01) and life‐time eczema (30.7% vs. 28.1%, p = 0.01) increased significantly. There was no significant change in prevalence of life‐time asthma, life‐time wheeze and current wheeze albeit a significant increase in severe asthma symptoms. We investigated a number of potential risk factors including sex, family history of atopy, sibship size, birth weight, respiratory tract infections, pet ownership and exposure to tobacco smoke. However, the increases in prevalence of rhinitis and eczema could not be entirely explained by the change of prevalence of these risk factors. The odds ratio OR for the study period remained significantly associated with current rhinitis (OR 1.31, 95% confidence intervals CI 1.17–1.46), current rhinoconjunctivitis (OR 1.63, 95% CI 1.41–1.87) and life‐time eczema (OR 1.30, 95% CI 1.16–1.45) after adjustment for these confounding variables using logistic regression model. Further study is warranted to elucidate the factors contributing to the observable change in the prevalence of rhinitis in our population.

Association between air pollution and asthma admission among children in Hong Kong.

Objective To examine the association of air pollutants with hospital admission for childhood asthma in Hong Kong.

Pulmonary sequelae in long-term survivors of bronchopulmonary dysplasia

Abstract Background : Bronchopulmonary dysplasia (BPD) is a common problem in premature babies. Long‐term sequelae are the main concerns.

Foetal Exposure to Maternal Passive Smoking Is Associated with Childhood Asthma, Allergic Rhinitis, and Eczema

Objective. We examined the hypothesis that foetal exposure to maternal passive smoking is associated with childhood asthma, allergic rhinitis, and eczema. Methods. The study was a population-based cross-sectional survey of Hong Kong Chinese children aged ≤14 years carried out in 2005 to 2006. Results. Foetal exposure to maternal passive smoking was significantly associated with wheeze ever (OR 2.05; 95% CI 1.58–2.67), current wheeze (OR 2.06; 95% CI 1.48–2.86), allergic rhinitis ever (OR 1.22; 95% CI 1.09–1.37), and eczema ever (OR 1.61; 95% CI 1.38–1.87). Foetal exposure to maternal active smoking was significantly associated with asthma ever (OR 2.10; 95% CI 1.14–3.84), wheeze ever (OR 2.46; 95% CI 1.27–4.78), and current wheeze (OR 2.74; 95% CI 1.24–6.01) but not with allergic rhinitis ever (OR 1.01; 95% CI 0.70–1.46) or eczema ever (OR 1.38; 95% CI 0.87–2.18). The dose response relationship between wheeze ever and current wheeze with increasing exposure, from no exposure to maternal passive smoking and then to maternal active smoking, further supports causality. Conclusion. There is significant association between foetal exposure to maternal passive smoking and maternal active smoking with childhood asthma and related atopic illnesses. Further studies are warranted to explore the potential causal relationship.

Prenatal Tobacco Exposure Shortens Telomere Length in Children

Introduction: Preliminary evidence suggests a possible association between prenatal tobacco exposure and telomere length in children. This study was conducted to investigate whether maternal smoking during pregnancy was associated with telomere shortening in their children and whether prenatal and childhood exposure to environmental tobacco had any impact on this association. Methods: This is a population-representative study on the association between prenatal tobacco exposure and telomere length in children. Ninety-eight Hong Kong Chinese children aged under 15 years with prenatal tobacco exposure and 98 age- and gender-matched controls were recruited from a population health study with stratified random sampling. Results: Telomere length in children with prenatal tobacco exposure was significantly shorter than in those with no exposure (mean T/S ratio = 24.9 [SD = 8.58] in exposed vs. 28.97 [14.15] in control groups; P = 0.02). A negative dose–response relationship was observed between the T/S ratio and tobacco exposure duration: the longer the duration of maternal smoking in pregnancy, the shorter the child’s telomere length. The association between the child’s telomere length and prenatal tobacco exposure remained significant after considering the influence of family socioeconomic status and exposure to environmental tobacco smoke during pregnancy and childhood. Conclusions: Prenatal tobacco exposure was associated with telomere shortening in children. As this may impose significant health impacts through fetal genetic programming, more efforts should be made to reduce fetal tobacco exposure by educating pregnant women to not smoke and motivating smokers to quit in early pregnancy. Implications: As reflected by telomere shortening, prenatal tobacco exposure in children can cause premature aging and increased health risks, which we suggest is entirely preventable. Not smoking during pregnancy or quitting smoking is critical to improving the health outcome of our future generations as prenatal tobacco exposure may affect children’s biological programming.

The Clinical Impact of Chromosomal Microarray on Paediatric Care in Hong Kong

Objective To evaluate the clinical impact of chromosomal microarray (CMA) on the management of paediatric patients in Hong Kong. Methods We performed NimbleGen 135k oligonucleotide array on 327 children with intellectual disability (ID)/developmental delay (DD), autism spectrum disorders (ASD), and/or multiple congenital anomalies (MCAs) in a university-affiliated paediatric unit from January 2011 to May 2013. The medical records of patients were reviewed in September 2013, focusing on the pathogenic/likely pathogenic CMA findings and their “clinical actionability” based on established criteria. Results Thirty-seven patients were reported to have pathogenic/likely pathogenic results, while 40 had findings of unknown significance. This gives a detection rate of 11% for clinically significant (pathogenic/likely pathogenic) findings. The significant findings have prompted clinical actions in 28 out of 37 patients (75.7%), while the findings with unknown significance have led to further management recommendation in only 1 patient (p<0.001). Nineteen out of the 28 management recommendations are “evidence-based” on either practice guidelines endorsed by a professional society (n = 9, Level 1) or peer-reviewed publications making medical management recommendation (n = 10, Level 2). CMA results impact medical management by precipitating referral to a specialist (n = 24); diagnostic testing (n = 25), surveillance of complications (n = 19), interventional procedure (n = 7), medication (n = 15) or lifestyle modification (n = 12). Conclusion The application of CMA in children with ID/DD, ASD, and/or MCAs in Hong Kong results in a diagnostic yield of ∼11% for pathogenic/likely pathogenic results. Importantly the yield for clinically actionable results is 8.6%. We advocate using diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility. Furthermore, it incorporates evidence-based medicine into the practice of genomic medicine. The same framework can be applied to other genomic testing strategies enabled by next-generation sequencing.

Chronic health problems and health-related quality of life in Chinese children and adolescents: a population-based study in Hong Kong

Objective We examined the association of different chronic physical and mental conditions, individually or comorbidly on health-related quality of life (QoL) in Chinese children aged ≤14 years in Hong Kong. Design Population-based cross-sectional survey. Participants Approximately 7500 Chinese children aged <14 years in Hong Kong. Interventions Nil. Primary and secondary outcome measures Various health concepts of validated Chinese version of Child Health Questionnaire (CHQ), a health-related QoL questionnaire in children. Result There was significant association of physical and mental health conditions, either individually or comorbidly, on the various concepts of CHQ. Children with mental health problems were apparently more affected than those with physical health problems. Chronic renal disease and congenital malformation were the physical health conditions associated with the lowest scores in CHQ concepts in children aged 5–10 years and aged 10–14 years, respectively. Behavioural problem was the mental health condition associated with the lowest score in CHQ concepts in both age groups. Conclusions Our study shows important information concerning the prevalence of different health conditions and its association, either individually or comorbidly on the QoL in a representative sample of Chinese children in HK.

Smoke-free legislation reduces hospital admissions for childhood lower respiratory tract infection.

Background Previous studies showed reduction of hospital admissions for asthma after implementation of comprehensive smoke-free legislation. We aimed to evaluate the impact of comprehensive smoke-free legislation implemented in Hong Kong in 2007 on hospital admissions for childhood lower respiratory tract infection (LRTI). Methods We obtained data on 75 870 hospital admissions for LRTI among children ≤18 years of age between January 2004 and December 2012 from all Hospital Authority hospitals. Using a negative binomial regression model, we assessed the impact of smoke-free legislation on admission counts. Results After legislation implementation, there was an immediate effect with a change in the admission count of −33.5% (95% CI −36.4% to −30.5%), and a change in time trend to −13.9% per year (95% CI −16.0% to −11.7%). Overall, the legislation was associated with a net 47.4% reduction in admission counts in the first year. We estimated that the legislation was associated with a reduction of 13 635 admissions in the first 6 years after implementation. The immediate reduction and change in time trend was more apparent among school-age than preschool children. Conclusions Implementation of comprehensive smoke-free legislation was associated with a significant reduction in hospital admissions for childhood LRTI.

Exome sequencing for paediatric-onset diseases: impact of the extensive involvement of medical geneticists in the diagnostic odyssey

Currently, offering whole-exome sequencing (WES) via collaboration with an external laboratory is increasingly common. However, the receipt of a WES report can be merely the beginning of a continuing exploration process rather than the end of the diagnostic odyssey. The laboratory often does not have the information the physician has, and any discrepancies in variant interpretation must be addressed by a medical geneticist. In this study, we performed diagnostic WES of 104 patients with paediatric-onset genetic diseases. The post-exome review of WES reports by the clinical geneticist led to a more comprehensive assessment of variant pathogenicity in 16 cases. The overall diagnostic yield was 41% (n = 43). Among these 43 diagnoses, 51% (22/43) of the pathogenic variants were nucleotide changes that have not been previously reported. The time required for the post-exome review of the WES reports varied, and 26% (n = 27) of the reports required an extensive amount of time (>3 h) for the geneticist to review. In this predominantly Chinese cohort, we highlight the importance of discrepancies between global and ethnic-specific frequencies of a genetic variant that complicate variant interpretation and the significance of post-exome diagnostic modalities in genetic diagnosis using WES. The challenges faced by geneticists in interpreting WES reports are also discussed.Pediatrics: Extra review of exome data boosts diagnostic yieldIn-depth reviews by clinical geneticists can improve the diagnostic accuracy of exome sequencing data for children with unexplained genetic disorders, especially in non-Western populations that are under-represented in genomic databases. Working with children predominantly of Han Chinese origin, Brian Chung from the University of Hong Kong and coworkers sequenced the entire protein-coding portion of the genome for 104 patients with pediatric-onset genetic disease. Specially trained geneticists analyzed the DNA data to resolve any ambiguous interpretations, link the molecular findings with clinical records, identify ethnic-specific differences and, when necessary, request additional assays. This extra review process was sometimes laborious, taking several hours of the physician’s time, but ultimately led to a more comprehensive assessment in 16 of the 43 diagnoses successfully made. This overall diagnostic yield—41%—was comparable to previous studies in other populations.

CFTR founder mutation causes protein trafficking defects in Chinese patients with cystic fibrosis

Cystic fibrosis (CF) is a rare condition in Asians. Since 1985, only about 30 Chinese patients have been reported with molecular confirmation.