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Vitamin D deficiency and insufficiency are highly prevalent among adolescents in Hong Kong, which is a sub-tropical city with ample sunshine. Vitamin D level is significantly correlated with key bone density and bone quality parameters. Further interventional studies are warranted to define the role of vitamin D supplementation for improvement of bone health among adolescents. The relationship between bone quality parameters and vitamin D (Vit-D) status remains undefined among adolescents. The aims of this study were to evaluate Vit-D status and its association with both bone density and bone quality parameters among adolescents. Three hundred thirty-three girls and 230 boys (12–16 years old) with normal health were recruited in summer and winter separately from local schools. Serum 25(OH) Vit-D level, bone density and quality parameters by Dual Energy X-ray Absorptiometry (DXA) and High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT), dietary calcium intake, and physical activity level were assessed. Sixty-four point seven percent and 11.4 % of subjects were insufficient [25 ≤ 25(OH)Vit-D ≤ 50 nmol/L] and deficient [25(OH)Vit-D

1. Prediction equations and normograms are established using incentive spirometry in a community cohort of 770 Hong Kong Chinese children aged 2 to 6 years. 2. All spirometric parameters depend mainly on standing height. Boys have higher values than girls. 3. Forced expiratory volumes depend on birth weight, place of birth, history of wheezing, and environmental tobacco smoke (ETS) exposure. 4. High urinary cotinine level as a biomarker of ETS exposure is noted in about one tenth of the children. 5. Urinary cotinine level is inversely associated with all spirometric parameters. This supports implementation of the smoking cessation programme.

1. Respiratory viruses and atypical bacteria were detected in 51.0% of Hong Kong children with asthma exacerbations, which was significantly higher than the detection rate of 27.3% in children with chronic stable asthma. 2. Co-infections of two or more respiratory pathogens were more commonly found in children with asthma exacerbations (10.7%) than in patients with stable asthma (2.6%). 3. Human rhinovirus infection was a significant risk factor for asthma exacerbations. 4. There was no significant association between the severity of asthma exacerbations and respiratory viral or atypical bacterial infections. 5. Routine use of macrolide antibiotics in the treatment of childhood asthma exacerbations should be discouraged.

Eczema lesions are characterized by impaired expression of antimicrobial peptides such as cathelicidin, which play crucial roles in the innate immune defence against cutaneous infections. LL-37 corresponds to amino acids 134-170 of human cathelicidin and is a multifunctional host defence molecule essential for normal immune responses to infection and tissue injury.The aim of this study was to investigate the relationship between childhood eczema and circulating LL-37 levels.One hundred and forty-four eczema children and 36 controls were recruited. Eczema severity was assessed by SCORing Atopic Dermatitis (SCORAD) and serum LL-37 concentration measured using enzyme immunoassay. Patients' skin hydration and transepidermal water loss at forearms were measured using Corneometer and Tewameter.Patients' mean SCORAD was 49.2 and their disease was classified as mild (n=28; 12.8%), moderate (n=95; 43.6%) and severe (n=95; 43.6%). Serum LL-37 concentrations did not differ between eczema patients and controls (mean: 832 pg/mL vs. 952 pg/mL, P=0.471). However, serum LL-37 concentrations increased with increasing eczema severity among the patients (P=0.005 for trend). This biomarker shows weakly positive correlation with patients' objective SCORAD (r=0.207, P=0.013) and age (r=0.170, P=0.041), but not skin hydration or transepidermal water loss (P0.09). Linear regression confirmed significant association between objective SCORAD and serum LL-37 when adjusted for age and gender as covariates (β=0.171, P=0.038). On the other hand, serum LL-37 did not differ between patients with and without heavy growth of staphylococci (P=0.151).Circulating LL-37 may be a biomarker for severity of childhood eczema, which supports the importance of innate immunity in eczema pathogenesis.

Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood.We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis.Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P0.05), with per allele odds ratios generally1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies.Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.

Cyclooxygenase-2 (COX-2) plays essential roles in inflammation. Previous studies have suggested associations between prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms and prostaglandins production in asthma.We have investigated the effects of Chinese tagging single nucleotide polymorphisms (SNPs) of PTGS2 on asthma traits in 299 Chinese asthmatic children and 175 controls.Plasma total and allergen-specific IgE were measured by enzyme immunoassay. PTGS2.8473T--C in the 3'-untranslated region of exon 10 and three tag SNPs covering most of the variations in PTGS2 haplotypes in Chinese were genotyped by restriction fragment length polymorphism.Among the four SNPs, only PTGS2.8473 showed significant association with asthma (P = 0.034) and atopy (P = 0.005 when compared with non-atopic controls; P = 0.023 with all controls). Carriers of the C allele had a 1.5-fold (95% confidence interval: 1.01-2.30) risk of developing asthma than those homozygous for the T allele. Multivariate regression revealed significant correlations between PTGS2.8473 and forced expiratory volume in 1 s (FEV(1); P = 0.002) and peak expiratory flow rate (PEFR; P = 0.001) with age and gender adjusted. Patients with the C allele of PTGS2.8473 had significantly lower FEV(1) (median: 90.0%vs 98.0%; P = 0.0047) and PEFR (70.0%vs 73.5%; P = 0.0065) than those homozygous for the T allele. No significant association between plasma total and allergen-specific IgE and these SNPs or with their haplotypes was found.PTGS2.8473 polymorphism is associated with asthma, atopy and lung function but not plasma IgE in Chinese children. This may help to explore the pharmacogenetics of COX-2 inhibitors.

Polymorphisms in several genes have been associated with asthma, atopy and bronchial hyperresponsiveness in white and Japanese populations. In this study we tested for associations of 11 polymorphisms with wheeze and asthma in 10-year-old Chinese schoolchildren.The subjects were 107 children who had wheeze in the last 12 months and 118 without wheeze in the last 12 months. They were randomly selected from 3110 children who took part in Phase II of the International Study of Asthma and Allergies in Childhood. These schoolchildren underwent questionnaire, spirometry and methacholine challenge testing.The A allele of the tumor necrosis factor-alpha (TNFA) G-308A polymorphism was significantly associated with wheeze in the last 12 months (odds ratio [OR] 2.1, P = 0.04) and current asthma (OR 2.6, P = 0.006). When stratified by gender, these associations were only seen in the female study participants. In girls, the OR for the TNFA-308A allele and wheeze in the last 12 months was 3.6 (P = 0.01) and for current asthma it was 6.0 (P = 0.0006).The A allele of the TNFA G-308A polymorphism was a risk factor for asthma-related phenotypes in girls but not boys.

OBJECTIVE This study aimed to determine the relationship between individual allergens with current wheezing and bronchial hyperresponsiveness (BHR) in schoolchildren from three chinese cities: Beijing, Guangzhou and Hong Kong. METHODS Community-based random samples of 10-yr-old schoolchildren from the 3 cities were recruited for study using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. The subjects were studied by parental questionnaires (n = 10,902), skin-prick tests (n = 3478), and methacholine challenge tests (n = 608). RESULTS The highest prevalence rates of wheezing in the past 12 months (Beijing, 3.8%; Guangzhou, 3.4%; Hong Kong, 5.8%) and atopy (Beijing, 23.9%; Guangzhou, 30.8%; Hong Kong, 41.2%, defined as havingor= 1 positive skin-prick tests,) were seen in schoolchildren from Hong Kong. The highest prevalence rates of BHR (Beijing, 33.2%; Guangzhou, 45.8%; Hong Kong, 30.7%) were seen in schoolchildren from Guangzhou. Multivariate-logistic regression analyses revealed that sensitization to Dermatophagoides pteronyssinus [odds ratio ((OR)) = 4.48; 95% confidence interval ((CI)); 3.02-6.66], cat ((OR) 2.85; 95% (CI) 1.24-6.50), Dermatophagoides farinae (DF) ((OR) 2.41, 95% (CI) 1.65-3.51) and Mixed grass pollen ((OR) 2.85, 95% (CI) 1.24-6.50) were significantly associate with current wheezing atopy ((OR) 1.29, 95% (CI) 0.74-2.24), was not an independent risk factor for current wheezing in children from any of the three cities. Furthermore, atopy ((OR) 2.53, 95% (CI) 1.93-6.97) were significantly associated with BHR. CONCLUSION The authors confirmed that sensitization to house dust mite and cat was significantly associated with current wheezing and bronchial hyperresponsiveness in Chinese schoolchildren.

To compare the diameters of Bacille Calmette-Guerin (BCG) scars between asthmatic (allergic) students and normal students, and to compare the diameters of BCG scars in children in rural Beijing area with those in urban Beijing area, and to compare the prevalence of asthmatic (allergic) symptoms and atopy between rural and urban Beijing students.Sampled by cluster-random Method, 819 urban school children and 1 044 rural school children aged 13 - 14 years were recruited for the Beijing arm of the phase III international study of asthma and allergies in childhood. The children answered the core questionnaires, and underwent skin prick test for 13 allergens, and were checked for BCG scars on their arms.(1) In both rural and urban Beijing students, the mean diameters of BCG scars in those with asthma (allergy) (asthma ever, wheeze ever, current wheeze within 12 months, hay fever ever, repeated rash ever, eczema ever, allergic rhinitis, atopy, high-sensitivity or were diagnosed asthma) were (7.0 +/- 2.1) mm-(8.8 +/- 2.8) mm, which were not significantly different from those of (7.2 +/- 2.7) mm-(8.2 +/- 2.2) mm in normal students (P0.05). (2) Compared to the urban students, the mean diameter of BCG scars in the rural students was (8.2 +/- 2.3) mm, significantly larger than that of (7.3 +/- 2.9) mm in the urban students (P0.01). The prevalence of asthma (allergy) (asthma ever, wheeze ever, current wheeze within 12 months, hay fever ever, repeated rash ever, eczema ever, allergic rhinitis, atopy, high-sensitivity or diagnosed asthma) were 0.6% - 11.4% in the rural Beijing students, significantly lower than that of 3.1% - 35.7% in urban Beijing schoolchildren (P0.01).The diameters of BCG scars were not significantly different between asthmatic (allergic) students and normal students. The diameters of BCG scars in the rural students were significantly larger than those in the urban students. The prevalence of asthma and allergy in the rural children were significantly lower than that in the urban students. The results suggest that there is difference in immunity between rural and urban children from early life, which may be caused by the different living environments.

Aims: To study the ocular manifestations and their severity in children with Graves9 disease. Methods: All patients with Graves9 disease having regular follow up in a paediatric endocrine clinic were recruited for the study. A comprehensive ophthalmic assessment including ocular motility, exophthalmometry, intraocular pressure (IOP), slit lamp, and fundus examinations was performed. Results: 83 patients (72 female, 11 male) aged 16 years or below were examined. All are Chinese. Ocular symptoms occurred in 12 patients. Ocular signs of ophthalmopathy were documented in 52 patients (62.7%). Most of them presented with eyelid abnormalities such as lid oedema, lid lag, and lagophthalmos, whereas lower lid retraction was the commonest clinical sign noted (38.6%). Diffuse conjunctival injection was found in four patients (4.8%). 10 patients (12.0%) had mild proptosis of less than 3 mm. Only one patient (1.2%) had limited extraocular motility in extreme gaze. Punctate epithelial corneal erosions were reported in 11 patients (13.3%). Conclusions: This is the largest series on the ocular complications of childhood Graves9 disease in the literature. Although 52 patients (62.7%) were identified with positive ocular changes, none of them had visual threatening complications or debilitating myopathy.

Graves' disease is associated with a polymorphism at position 49 in exon 1 of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene in Caucasians and Japanese. A high incidence of childhood Graves' disease has been documented in Hong Kong Chinese. The aims of this study were to investigate the CTLA-4 gene A-G polymorphism association in Chinese children with Graves' disease.One hundred and twenty-three Chinese children with Graves' disease (104 girls and 19 boys) and 158 racially matched healthy controls were recruited for the study. Genomic DNA was extracted from venous blood samples. The dimorphism at position 49 A-G was analysed by polymerase chain reaction, single-strand conformation polymorphism and restriction fragment-length polymorphism analysis.The genotype distribution and allele frequencies of children with Graves' disease differed significantly from those of the controls (P = 0.0023 and P = 0.022, respectively). The presence of at least one G allele (GG or AG) was associated with an increased risk of Graves' disease (OR = 6.8, 95% CI = 2.0-36.1; P = 0.001).This study confirms that CTLA-4 49 A-G polymorphism is associated with Graves' disease in Chinese children. The CTLA-4 49 G allele confers an increased risk of childhood Graves' disease.

When treatment with diazoxide and somatostatin for persistent hyperinsulinaemic hypoglycaemia of infancy failed, subtotal pancreatectomy was performed on a neonate on day 41. The pancreatic tissue was saved and used for immunohistochemical and cell culture studies. The initial immunohistochemistry of beta cells for insulin was negative, using a 1 in 200 dilution of insulin antiserum, but positive results were obtained with an increased concentration of the antiserum. The insulin to somatostatin cell ratio in islets of Langerhans was about 1:1, with no somatostatin cells outside the islets. Glucose stimulated insulin secretion in a concentration dependent manner in vitro. Isobutyl methyl xanthine doubled insulin secretion, but lithium had no effect. The glucose stimulated insulin secretion was inhibited by somatostatin, epinephrine, and in the absence of Ca2+. In view of the normal in vitro responses of beta cells to various secretory analogues, the lack of responsiveness to somatostatin analogue before pancreatectomy may not have been due to deficiency or resistance to somatostatin, but to beta cell hyperplasia overwhelming the paracrine regulatory mechanism(s).

Goitre is common among growing children and adolescents. To define the aetiology of goitre in adolescents of Hong Kong and to examine their current level of iodine intake, this cross-sectional survey of goitre in high school students was performed and urine samples were collected for the analysis of iodine excretion. Screening examinations were carried out in 2439 secondary school students aged 12-18 years from ten randomly selected high schools in Hong Kong. Blood samples were obtained from all goitrous subjects for the determination of serum TSH, free T4 and thyroid antibodies. We obtained 476 random urine samples and 80 24-h urinary collections for the analysis of iodine excretion. Of these, 85 subjects (3.5%) had goitre, 70 had simple goitre. Chronic lymphocytic thyroiditis was found in ten subjects. Two had Graves' disease and three had nodular goitre. The median urinary iodine concentration for the random urine samples was 190 microg/l (1.50 micromol/l) or 158 microg/g creatinine. The median 24-h urinary excretion of iodine was 189 microg (1.49 micromol) per day.This cross-sectional study demonstrates the spectrum of thyroid disease in Chinese adolescents in Hong Kong. Their urinary iodine excretion was adequate and much higher than those of children from many European countries and coastal cities of China.

SummaryIn a 9-year retrospective review of goitre in Chinese children in Hong Kong, 84 children and adolescents were identified. There was a female predominance with a male:female ratio of 1:5.5. The majority of patients (95%) were found to have diffuse enlargement of the thyroid gland. Forty-nine were found to have Graves' disease. The mean age of presentation of patients with Graves' disease was 11.34 years. Forty-three of them were found to have thyroid autoantibodies. Only two cases of autoimmune thyroiditis with thyroid autoantibodies were diagnosed. The other causes of goitre include simple colloid goitre, multinodular goitre and suppurative thyroiditis. The spectrum of disease causing goitre in Chinese children is thus quite different from that reported in Caucasian children in developed countries. Further studies are necessary to define the genetic or environmental factors resulting in the observed differences.