Ting Fan Leung

Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong

Aims To assess the relationship between levels of ambient air pollutants and hospitalization rates for asthma in Hong Kong (HK).

The C−159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children

Activation of macrophages through CD14 by microbes is crucial in inducing immunity by type 1 T helper cells. A C‐to‐T polymorphism at position −159 of CD14 was associated with serum total IgE level in Caucasians but not in Japanese subjects. The objective of this study is to determine whether this polymorphic marker is associated with atopy and asthma phenotypes in Chinese children. Restriction fragment length polymorphism was used to characterize CD14/−159 genotypes. Microparticle immunoassay was used to measure serum total IgE level; fluorescent enzyme immunoassay was performed to measure serum concentrations of specific IgE to aeroallergens; and enzyme‐linked immunosorbent assay was used to measure serum levels of soluble CD14 (sCD14). Lung function in asthmatics was assessed by spirometry. Two hundred and fifty‐eight patients and 92 control children were recruited. Their mean serum total IgE concentrations were 331 and 74 kIU/l, respectively (p < 0.0001). Atopy, defined as the presence of at least one allergen‐specific IgE in serum, was found in 220 (85%) patients and in 41 (45%) controls (p < 0.0001). Serum sCD14 levels were significantly associated with CD14/−159 genotypes (p = 0.004). Atopic subjects with CC genotype in CD14/−159 had the highest serum total IgE levels compared with CT and TT genotypes, with the respective mean values being 661, 427 and 380 kIU/l (p = 0.015). Similarly, a higher proportion of subjects with CC genotype had increased serum total IgE concentration (p = 0.039). This polymorphic marker was not associated with asthma or aeroallergen sensitization in our cohort. Our results suggest that the C−159T of CD14 was associated with serum total IgE concentration in atopic Chinese children.

Incidence, risk factors and outcome of varicella-zoster virus infection in children after haematopoietic stem cell transplantation.

We report a retrospective analysis of VZV infection after haematopoietic stem cell transplantation (HSCT) in children. Thirty-three (30%) of the total 109 children who were transplanted during a 7 year period developed post-transplant VZV infection. Twenty-four of these 33 (73%) children had VZV infection within 1 year following HSCT. The cumulative incidences of post-transplant VZV infection at 1 and 5 years were 26% and 45%, respectively. The positive and negative predictive values of pretransplant VZV serology in recipients on the development of HZ following HSCT were 39% and 88%, respectively. Pretransplant VZV seropositivity in recipients was the only risk factor for post-transplant herpes zoster (HZ) infection on multivariate analysis. All patients responded to acyclovir. The median duration of VZV infection was 5 days. Three (11%) and one (3%) children with HZ developed visceral dissemination and post-herpetic neuralgia, respectively. No mortality was directly attributed to VZV infection. VZV infection remains a major cause of morbidity in children after HSCT. Further studies are warranted to evaluate the potential use of VZV vaccine in these children. Bone Marrow Transplantation (2000) 25, 167–172.

Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia.

BACKGROUND Little is known about the virological and inflammatory responses of severe pandemic 2009 influenza A(H1N1) virus pneumonia during antiviral treatment. METHODS In a prospective observational study, we recruited consecutive adults hospitalized with confirmed pandemic 2009 H1N1 infection during a 16-week period. Nasopharyngeal aspirate and non-respiratory samples (blood, stool and urine) were collected at presentation, and serial nasopharyngeal flocked swabs (NPFS) and tracheal aspirates (TA) were collected after initiating oseltamivir treatment for quantitative viral RNA assay, using real-time reverse transcriptase-PCR. Serial plasma samples were collected for cytokine/chemokine assay using cytometric bead array. Patients with severe pneumonia (lung infiltrates and hypoxaemia) were compared to those with milder illnesses. RESULTS A total of 66 patients were studied (mean age 43 ±20 years); 28 (42%) developed severe pneumonia, of whom 10 (15%) required intubation. Severe pneumonia was associated with older age, dyspnoea, delayed presentation >2 days from onset, extrapulmonary virus detection (13-28%) and higher viral concentration despite late-presentation (multiple linear regression, β=0.94, 95% confidence interval 0.15-1.74; P=0.02). Patients with severe pneumonia exhibited slow viral clearance with oseltamivir treatment, particularly in the lower respiratory tract (median [interquartile range] durations of RNA positivity after antiviral initiation were NPFS 6.0 days [3.0-8.0], TA 11.0 days [7.8-14.3] versus milder illness group NPFS of 2.0 days [1.0-3.0] days; P<0.01). High viral load in lower respiratory tract despite upper-tract RNA negativity and viral rebound after stopping treatment were noted in some patients. H275Y mutation was absent. High plasma levels of interleukin (IL)-6, CXCL-8 (IL-8), CCL2 (monocyte chemoattractant protein-1) and soluble tumour necrosis factor receptor-1 were observed, which correlated with the extent and progression of pneumonia in hospital. CONCLUSIONS In severe 2009 H1N1 pneumonia, viral clearance is slow with treatment, particularly in the lower respiratory tract. A more sustained antiviral regime appears warranted.

Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers: epidemiology, clinical spectrum and risk factors

The epidemiology of adverse food reactions (AFRs), including the potentially life‐threatening food allergy (FA), in Asia is unclear. AFR is believed to be less prevalent than in Caucasians. This study determines the prevalence, clinical features and risk factors for parent‐reported AFR in Chinese pre‐school children in Hong Kong. Children aged 2–7 yr living in Hong Kong were recruited through local nurseries and kindergartens to ascertain the occurrence and clinical spectrum of AFR and other atopic disorders. Subjects’ parents answered a self‐administered questionnaire that was modified and validated based on the International Study of Asthma and Allergy in Childhood. A total of 3827 children from 21 nurseries and kindergartens returned the study questionnaires, and information on AFR was analyzable for 3677 (96.1%) children. The prevalence rates of parent‐reported AFR and parent‐reported, doctor‐diagnosed AFR were 8.1% and 4.6%, respectively, whereas 5.0% of pre‐schoolers had doctor‐diagnosed asthma. The six leading causes of AFR were shellfish (15.8%), egg (9.1%), peanut (8.1%), beef (6.4%), cow’s milk (5.7%), and tree nuts (5.0%). When compared with children born and raised in Hong Kong, children born in mainland China (n = 253) had less parent‐reported AFR (4.0% vs. 6.7%; p = 0.016). On logistic regression, parent‐reported AFR was associated with younger age (p = 0.010), born in mainland China (p = 0.038), and AFR history in father (p = 0.001), mother (p < 0.001), siblings (p = 0.020), and paternal history of rhinitis (p = 0.044). This study shows that AFR is a common atopic disorder in Hong Kong pre‐school children, and prevalence rates are comparable to the Caucasians.

Comparison of Skin Hydration Evaluation Sites and Correlations among Skin Hydration, Transepidermal Water Loss, SCORAD Index, Nottingham Eczema Severity Score, and Quality of Life in Patients with Atopic Dermatitis

AbstractBackground:Atopic dermatitis (AD) is characterized by dryness of the skin, pruritus and involvement of the skin flexures. Skin hydration (SH) and integrity, as measured by transepidermal water loss (TEWL), are important parameters for objectively quantifying AD research. Objectives:To evaluate if sites in the forearm are equivalent to the antecubital fossa for standard SH and TEWL measurements; and to determine the correlations among these measurements and scores of disease severity and quality of life. Methods:We evaluated SH and TEWL under standardized conditions at three common measurement sites in the forearm (antecubital flexure, 2 cm below the antecubital flexure, mid-forearm), and determined the SCORing Atopic Dermatitis (SCORAD) score, Nottingham Eczema Severity Score (NESS), and Children’s Dermatology Life Quality Index (CDLQI). Results:Significant correlations between clinical scores, SH, and TEWL were obtained at a site 2 cm below the antecubital fossa (r = -0.553, p < 0.001 for SH and SCORAD; r = 0.596, p <0.001 for TEWL and SCORAD). SH and TEWL were also correlated with long-term severity of AD as measured by NESS (r = -0.494, p = 0.001 for SH; r = 0.430, p = 0.004 for TEWL), while TEWL was significantly correlated with CDLQI (r = 0.323, p = 0.035). Overall, similar significant correlations were obtained at the mid-forearm, but less so at the antecubital fossa. Conclusion:In AD research, three sites on the forearm appear to be convenient for determination of SH and TEWL. This is the first report to demonstrate that significant correlations are obtained among acute and chronic scores of AD disease severity, quality of life, and the bioengineering parameters

Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children.

Chemokines are responsible for the trafficking of leukocytes to sites of inflammation. Serum chemokine levels were previously shown to be increased in adult patients with atopic dermatitis (AD). We tested whether serum concentrations of chemokines, including macrophage‐derived chemokine (MDC), thymus and activation‐regulated chemokine (TARC), eotaxin (EOX), interferon gamma inducible protein 10 (IP‐10) and monocyte chemotactic protein 1 (MCP‐1), are useful inflammatory markers for assessing AD severity in infants and young children. To investigate this, we assessed the severity of AD clinically using the SCORing Atopic Dermatitis (SCORAD) index system. Serum chemokine concentrations were determined by sandwich enzyme immunoassay. Twenty AD patients with a median age of 2.1 years [interquartile range (IQR): 0.6–4.2] were recruited. Their SCORAD score was 23.5 (12.5–33.5). Serum concentrations of MDC, TARC, EOX, IP‐10 and MCP‐1 were 2551 (1978–3935), 1469 (1125–3070), 68 (57–85), 126 (101−226) and 518 (419–614) pg/ml, respectively. Serum MDC levels correlated with SCORAD (r = 0.608, p = 0.004) and its extent (r = 0.629, p = 0.003) and intensity (r = 0.557, p = 0.011) components. Serum TARC concentration showed weaker correlation with extent (r = 0.474, p = 0.035) and intensity (r = 0.465, p = 0.039) of skin involvement but not SCORAD. The median serum levels of MDC (3131 vs. 2394 pg/ml; p = 0.031) and EOX (80 vs. 61 pg/ml; p = 0.046) were also higher in children with moderate as compared with mild AD. The other chemokines did not correlate with AD severity. In conclusion, our results suggest that serum MDC concentration may be a useful inflammatory marker for assessing AD severity in infants and young children.

The relation between obesity and asthmatic airway inflammation

Epidemiologic studies suggest increased asthma prevalence in obese subjects. However, the relation between obesity and airway inflammation remains unclear. This cross‐sectional study aims to investigate the relation between obesity indices and exhaled nitric oxide (ENO) and leukotriene B4 (LTB4) in children with asthma. Asthmatic patients aged 7–18 yr old were recruited. Weight‐for‐height Z score was calculated from anthropometry. ENO was measured by online single‐breath method using a chemiluminescence analyzer, whereas LTB4 concentrations in exhaled breath condensate (EBC) were quantified using competitive enzyme immunoassay. Ninety‐two asthmatics and 23 controls were recruited. The mean ENO and LTB4 concentrations in EBC were higher in asthmatic patients (87 p.p.b. and 40.5 pg/ml) than controls (25 p.p.b. and 18.7 pg/ml) (p < 0.0001 for both). Obesity, as defined by weight >120% median weight‐for‐height, was not associated with any alteration in ENO or LTB4 concentrations in patients with asthma. Besides, these inflammatory markers did not differ between asthmatics in the highest and lowest quartiles of weight‐for‐height Z score. On multivariate analysis, ENO showed significant correlation with age (β = 0.511, p < 0.0001), peripheral blood eosinophil count (β = 0.222, p = 0.019), plasma total IgE concentration (β = 0.187, p = 0.050) and forced expiratory volume in 1‐s (FEV1; β = −0.221, p = 0.014). None of the factors was associated with LTB4 concentration in EBC. In conclusion, ENO and LTB4 concentration in EBC are increased in childhood asthma. However, these inflammatory markers did not differ between obese and non‐obese children with asthma.

Steroid fears in children with eczema.

Background: Topical glucocorticoids (GCs) are the mainstay of treatment for eczema, but GC phobia and fears are very common among the parents of paediatric patients. Aim: To survey the nature and extent of “fears” of GC use, and to evaluate if disease severity is associated with such fears. Methods: Patients with eczema managed in the paediatric dermatology outpatient clinic of a university hospital were recruited in this survey. Disease severity and various aspects of belief and practices of GC use were assessed with the Nottingham Eczema Severity Score and a questionnaire. Results: GC “fears” were present in two fifths of informants with non‐eczematous skin disease and mild eczema, but three fifths in moderate‐to‐severe disease. Requests for steroid‐sparing medications (such as tacrolimus or pimecrolimus) had been made in nearly 50% of cases with moderate‐to‐severe eczema, and many parents would wait until eczema had worsened or apply GC only as a last resort to avoid potential side effects. “Fears” were predominantly interpersonal and rarely iatrogenic in nature. Skin problems (in particular skin thinning) and adverse effects on growth were the side effects of GC of most concern. However, fewer than half of the informants had discussed their concerns with doctors.

Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4.

Aims/hypothesisMost genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.MethodsWe performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.ResultsWe identified CDKN2A/B and four novel type 2 diabetes association signals with p < 1 × 10−5 from the meta-analysis. Thirteen variants within these four loci were followed up in two independent Chinese cohorts, and rs10229583 at 7q32 was found to be associated with type 2 diabetes in a combined analysis of 11,067 cases and 7,929 controls (pmeta = 2.6 × 10−8; OR [95% CI] 1.18 [1.11, 1.25]). In silico replication revealed consistent associations across multiethnic groups, including five East Asian populations (pmeta = 2.3 × 10−10) and a population of European descent (p = 8.6 × 10−3). The rs10229583 risk variant was associated with elevated fasting plasma glucose, impaired beta cell function in controls, and an earlier age at diagnosis for the cases. The novel variant lies within an islet-selective cluster of open regulatory elements. There was significant heterogeneity of effect between Han Chinese and individuals of European descent, Malaysians and Indians.Conclusions/interpretationOur study identifies rs10229583 near PAX4 as a novel locus for type 2 diabetes in Chinese and other populations and provides new insights into the pathogenesis of type 2 diabetes.