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Biomedical subjects

Gary W K Wong

Publications and source records attributed to Gary W K Wong.

At least 19 recordsLinked to original sources

Overweight, family history of diabetes and attending schools of lower academic grading are independent predictors for metabolic syndrome in Hong Kong Chinese adolescents.

BACKGROUND: Overweight and metabolic syndrome (MES) are emerging in both adult and paediatric populations. AIMS: To study the prevalence of and associated risk factors for the MES, using the National Cholesterol Education Program definition, among Hong Kong Chinese adolescents studying in secondary schools. METHODS: This was a cross-sectional, population-based study. A sample of 2115 Chinese adolescents was randomly selected from 14 secondary schools throughout Hong Kong. Data on anthropometric parameters, fasting blood and urine samples were collected in the school setting. Information regarding the adolescent's family history of diabetes, perinatal history, socioeconomic status and school grading was evaluated. RESULTS: The prevalence of MES was 2.4% (95% confidence interval (CI) 1.8 to 3.1), with no significant difference between boys (2.9%) and girls (2%). The prevalence of various components of MES was 32.2% (30.2 to 34.2) for hypertension, 10.9% (9.6 to 12.2) for increased triglyceride, 9.0% (7.8 to 10.2) for central adiposity, 2.4% (1.7 to 3) for low high-density lipoprotein cholesterol and 0.3% (0.1 to 0.6) for impaired fasting glucose. On multivariate analysis, overweight (odds ratio 32.2; 95% CI 13.2 to 78.4), positive family history of diabetes (4.3; 1.3 to 14.1) and studying at schools of lower academic grading (5.5; 2.2 to 13.7) were found to be independent risk factors for MES. CONCLUSION: A comparable prevalence of MES (2%) is observed in our study group Chinese adolescent girls and in US girls (2.1%), but a lower prevalence in Chinese boys (2.9%) than in US boys (6.1%). In our study, 41.8% harbour at least one component of the syndrome. Both families and schools should be alerted to this growing epidemic.

Adolescent↗

Clinical and technical factors affecting pH and other biomarkers in exhaled breath condensate.

Exhaled breath condensate (EBC) pH appears to be a robust measure of asthma. However, the association between EBC pH and clinical factors and airway inflammatory markers remains unclear. The objectives of this study were to investigate the factors determining EBC pH in asthmatic children, and the reproducibility and effects of collection devices on EBC pH in nine healthy, nonsmoking adults. EBC was collected once from asthmatic children using EcoScreen, and from adults over 3 consecutive days using both RTubes and EcoScreen. EBC pH was measured immediately in non-deaerated samples by microelectrode pH meter. Concentrations of 8-isoprostane, cysteinyl leukotrienes (cys-LT), and leukotriene B4 (LTB4) were measured using enzyme immunoassay. Exhaled nitric oxide concentration (FeNO) was measured by chemiluminescence. Fifty-eight asthmatics (16 intermittent, 12 mild persistent, and 30 moderate-to-severe persistent) were recruited. EBC pH was lower among patients with moderate-to-severe persistent than intermittent asthma (P = 0.046). This marker correlated inversely with disease severity score (rho = -0.276, P = 0.036), but not FeNO or other EBC biomarkers. Bland-Altman analyses found pH but not other EBC biomarkers to be reproducible, which were confirmed by its low coefficient of variation (2.7%; range, 0.4-5.2%). There was poor correlation between pH in EBC collected by RTube and EcoScreen (rho = 0.059, P = 0.784). Factor analysis selected four factors that explained 67.5% of the total variance, and EBC pH clustered with both cys-LT and LTB4. In conclusion, our results suggest that pH in non-deaerated EBC is influenced by asthma severity in children. EBC pH measurement is reproducible, but is dependent on the collection devices used.

Adolescent↗

Lack of association between NOS2 pentanucleotide repeat polymorphism and asthma phenotypes or exhaled nitric oxide concentration.

Nitric oxide (NO) plays an immunoregulatory role in balancing cellular immunity. The expression of inducible nitric oxide synthase gene (NOS2) is upregulated upon exposure to proinflammatory cytokines and microbial exposure. The (CCTTT)n polymorphism in NOS2 promoter confers protection against infections and immunological disorders including atopy. We investigated the association between (CCTTT)n and asthma traits in Chinese children. Asthmatic children between 5 and 18 years of age and non-allergic controls were recruited. Plasma total and specific IgEs were measured by immunoassays, and exhaled NO concentration was quantified online by chemiluminescence. NOS2 (CCTTT)n was genotyped by GeneScan analysis. The mean (SD) age of 291 asthmatics and 172 controls were 11.1 (3.8) years and 11.6 (4.0) years, respectively (P = 0.259). NOS2 (CCTTT)n followed Hardy-Weinberg equilibrium in both groups, and its uni-modal allele distribution peaks at 12-repeat. Significant interethnic differences in (CCTTT)n alleles were observed, with our Chinese having less 13-repeat (Pc = 0.022) but more 17-repeat (Pc = 0.033) than Caucasians. The frequency of 14-repeat allele was similar in our Chinese as compared to Japanese (Pc = 0.32). Multivariate regression analyses failed to detect any association between this polymorphic marker and asthma diagnosis (P = 0.949), atopy (P = 0.305), IgE sensitization to aeroallergens (P > 0.2 for all), or FeNO (P = 0.847). These findings do not support NOS2 to be a major candidate gene for asthma or IgE-mediated allergic diseases in Chinese children.

Asthma↗

Genetic association study between mbl2 and asthma phenotypes in Chinese children.

Mannose-binding lectin (MBL), a member of the innate immune system, initiates complement deposition on microbial surfaces. MBL deficiency is associated with severe respiratory infections. Polymorphisms in the MBL gene (mbl2) were associated with the susceptibility and severity of autoimmune diseases. This study investigated whether mbl2 polymorphisms at positions -550 and -221 and at codon-54 are associated with asthma phenotypes in Chinese children. Asthmatics aged 5-18 yr and non-allergic controls were eligible, and their plasma total and allergen-specific immunoglobulin E (IgE) concentrations were measured by micro-particle immunoassay and fluorescent enzyme immunoassay. mbl2 polymorphisms were genotyped by restriction fragment length polymorphism. Three hundred and seventeen asthmatic children and 140 controls were recruited, with their mean (s.d.) log-transformed plasma total IgE being 2.61 (0.61) and 1.77 (0.77), respectively (p < 0.0001). Polymorphisms at -550 and codon-54 (p < 0.0001 for both) but not at -221 (p = 0.534) of mbl2 were significantly associated with plasma MBL concentrations. mbl2 genotypes were not associated with asthma, atopy, sensitization to individual aeroallergens or spirometric variable. Subjects with LYB haplotype had the lowest plasma MBL concentrations (p < 0.0001), but two- and three-loci mbl2 haplotypes were also not associated with asthma diagnosis. However, patients with LY and LYB haplotypes were less likely to be atopic (p = 0.006 and 0.031). Subjects with LY and LYA were also less likely to be sensitized to cockroach (p = 0.035 and 0.047). The latter three associations became insignificant when adjusted for multiple comparisons. Despite the importance of MBL in innate immunity, our mbl2 polymorphisms only show weak association with asthma and atopy in children.

Adolescent↗

[Disparity of asthma prevalence in Chinese schoolchildren is due to differences in lifestyle factors].

OBJECTIVE: To investigate the environmental lifestyle risk factors which may explain the disparity of asthma prevalence in the Chinese population. METHODS: In a cross-sectional study, 10 902 schoolchildren were recruited from Hong Kong (n = 3110), Beijing (n = 4277), and Guangzhou (n = 3565) using the ISAAC Phase II protocol. The average age of the children among three cities was 10.1-10.4 years and 50%-53% were male. Each subject was given an ISAAC Phase II questionnaire to be completed by the parents or guardians. Random subgroups of at least 1000 children from each city, added up to 3479 children underwent skin-prick testing. The sensitivity to eight common aeroallergens was assessed. Logistic regression analysis was used to determine the environmental and lifestyle risk factors for asthma and atopy. RESULTS: The prevalence of wheezing in the past 12 months (Hong Kong, 5.8%; Beijing, 3.8%; Guangzhou, 3.4%) was significantly higher in schoolchildren from Hong Kong than that from the Mainland of China (OR 1.64, 95% CI 1.35-1.99). Multivariate logistic regression analyses revealed that the use of gas cooking (OR 2.08, 95% CI 1.32-3.26), foam pillow (OR 1.94, 95% CI 1.19-3.16), and house dampness (OR 1.84, 95% CI 1.25-2.71) were significant risk factors for "current wheezing". The use of cotton quilt (OR 0.70, 95% CI 0.56-0.87), breast-feeding (OR 0.79, 95% CI 0.66-0.96), and attendance of daycare (OR 0.73, 95% CI 0.59-0.88) were protective factors against "current wheezing". When a summary measure of these variables was introduced into a regression model, the Mainland residency was no longer associated with "current asthma" or "current wheezing" suggesting that either these factors or other unmeasured factors associated with above factors are responsible for the lower prevalence of asthma in the Mainland of China. CONCLUSION: Several environmental and lifestyle factors represented characteristic of life in Mainland of China, including breast feeding, attendance of daycare, use of cotton quilt, use of pillow other than foam pillow, use of cooking fuel other than gas, and the absence of damp spots on the walls or ceiling, were the significant risk factors contributed to the disparity of asthma prevalence in children from Hong Kong and the Mainland of China.

Asthma↗

Gene-gene interactions for asthma and plasma total IgE concentration in Chinese children.

BACKGROUND: Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene-gene interactions could provide insight into asthma pathophysiology. OBJECTIVE: We investigated the interaction among 12 different loci in 8 candidate genes and asthma and increased plasma total IgE concentrations in 240 Chinese asthmatic subjects and 140 control subjects. METHODS: Genotyping was performed by means of RFLP analysis. Multifactor dimensionality reduction and logistic regression were used to analyze gene-gene interactions. RESULTS: A significant interaction was found between R130Q in the IL-13 gene (IL13) and I50V in the IL-4 receptor alpha gene (IL4RA) on the risk of asthma, with a cross-validation consistency of 10 of 10 and a prediction error of 33.7% (P = .014). The odds ratio of the high-risk to low-risk group was 2.6 (95% CI, 1.4-5.0; P = .004). For increased plasma total IgE concentration, the best 2-locus model consisted of R130Q in IL13 and C-431T in the thymus and activation-regulated chemokine gene (TARC). This model showed a maximum cross-validation consistency of 10 and a minimum prediction error of 36.1% (P = .022). The odds ratio of the high-risk to low-risk group was 3.9 (95% CI, 2.0-7.7; P = .0001). Logistic regression revealed significant interactions between IL13 and IL4RA for asthma (P = .042) and IL13 and TARC for increased total IgE concentration (P = .012). CONCLUSIONS: Our data suggest significant interactions between IL13 and IL4RA for asthma and IL13 and TARC for increased plasma total IgE concentrations in Chinese children.

Adolescent↗

Exhaled breath condensate levels of 8-isoprostane, growth related oncogene alpha and monocyte chemoattractant protein-1 in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) patients have increased neutrophils and macrophages in their lungs, and inflammation of the airway is related to oxidative stress. This study assessed the levels of 8-isoprostane (an oxidative stress marker) and chemokines related to neutrophil and monocyte inflammation (growth-related oncogene alpha [GROalpha] and monocyte chemoattractant protein-1 [MCP-1]) in the airway of ex-smoking COPD patients by exhaled breath condensate (EBC) collection. Thirty-two (28 males) stable COPD patients (14 with FEV(1) 50% [Group 1], 18 with FEV(1) <50% predicted [Group 2]) and 18 non-smoking age and sex-matched controls were studied in this cross-sectional study. EBC was collected using the EcoScreen (Jaeger, Germany) during 10 min of tidal breathing with the nose clipped. Concentrations of 8-isoprostane, GROalpha and MCP-1 were measured by enzyme immunoassays. COPD patients had a higher concentration of 8-isoprostane than controls (COPD versus control, P<0.001; Group 1 versus Group 2, P=0.045). 8-isoprostane increased across the groups from normal, Group 1 to Group 2 (r=0.64, P<0.001). The median intraquartile range (IQR) levels in pg/ml for GROalpha were 45.3(44.5-46.5), 45.4(44.5-46.0), 46.0(45.6-47.3), whereas MCP-1 levels were 5.3(5.2-5.9), 6.2(5.4-6.9) and 5.7(5.5-6.4) in Group 1, Group 2 COPD and control subjects, respectively. GROalpha level was lower in COPD patients when compared to controls (P=0.01). MCP-1 level did not differ between COPD and the control group. 8-isoprostane level, but not GROalpha and MCP-1, in EBC was increased in COPD patients with poorer lung function. This suggests an increased oxidative stress in the airway in patients with more severe COPD.

Aged↗

Analysis of growth factors and inflammatory cytokines in exhaled breath condensate from asthmatic children.

BACKGROUND: Vascular endothelial growth factor (VEGF), AA isoform of platelet-derived growth factor (PDGF-AA), and epidermal growth factor (EGF) are involved in the pathogenesis of airway inflammation in asthma. These molecules are closely associated with cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-4. This study investigates the relation between childhood asthma and levels of these mediators in exhaled breath condensate (EBC). METHODS: EBC was collected from asthmatic children and controls using a disposable collection kit, and the concentrations of VEGF, PDGF-AA, EGF, TNF-alpha and IL-4 in EBC were measured using sandwich enzyme immunoassays. Exhaled nitric oxide concentration was measured by a chemiluminescence analyzer. RESULTS: Thirty-five asthmatic patients aged between 7 and 18 years and 11 controls were recruited. Sixteen patients had intermittent asthma (IA) whereas 19 of them suffered from persistent asthma (PA). A significant correlation was found between IL-4 and TNF-alpha in EBC (rho = 0.374, p = 0.010). PDGF-AA levels in EBC were higher in subjects with diminished FEV1 (p = 0.023) whereas IL-4 concentrations were increased in asthmatics (p = 0.007) as well as subjects with increased plasma total IgE (p = 0.033). Patients with PA receiving high-dose inhaled corticosteroid (ICS) had higher EBC IL-4 concentration than those on low-dose ICS (p = 0.007). Linear regression revealed that PDGF-AA levels in EBC were negatively associated with FEV1 percentage (beta = -0.459, p = 0.006) among the asthmatic patients. CONCLUSIONS: IL-4 in EBC is increased in childhood asthma, and growth factors are detectable in a significant proportion of these children. Increased PDGF-AA is found in asthmatics with more severe airflow limitation.

Adolescent↗

CD14 and toll-like receptors: potential contribution of genetic factors and mechanisms to inflammation and allergy.

Innate and adaptive immune responses evolve as protective mechanisms against infectious microorganisms in humans. CD14 and toll-like receptors (TLRs) are examples of pattern recognition receptors that detect antigenic molecules on the surface of gram-positive (peptidoglycans, lipoteichoic acid) and gram-negative (lipopolysaccharide) bacteria. In vitro studies suggest that lipopolysaccharide is a potent inducer of interleukin-12 production that is mediated by both CD14 and TLR4. The associated increase in interferon-gamma steers our immune system away form the allergy-driven type-2 helper T cell phenotype. Epidemiological studies that shed light on the possible protective influences of natural microbial exposure on asthma and atopy development will be discussed. Recent insights into the complex mechanisms of human innate immunity suggest that genetic variability in genes encoding its components may alter the susceptibility to develop atopic disorders and other complex human diseases. The findings of these genetic association studies will be presented. Although highly conserved across a wide range of species, innate immunity genes demonstrate considerable inter-ethnic variability predominantly in the form of single nucleotide polymorphisms. The frequencies of these polymorphisms in CD14 and TLR genes in different ethnic groups will be discussed. Genetic variation in these genes may also play a role in the development of other human diseases that have an inflammatory component. Lastly, the prospect of using immunomodulatory agents targeting on the innate immunity to treat or even prevent asthma and other allergic diseases will be discussed.

Animals↗

Factors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey.

OBJECTIVE: To determine the factors associated with difference in prevalence of asthma in children in different regions of China. DESIGN: Multicentre epidemiological survey. SETTING: Three cities in China. PARTICIPANTS: 10,902 schoolchildren aged 10 years. MAIN OUTCOME MEASURES: Asthma and atopic symptoms, atopic sensitisation, and early and current exposure to environmental factors. RESULTS: Children from Hong Kong had a significantly higher prevalence of wheeze in the past year than those from Guangzhou and Beijing (odds ratio 1.64, 95% confidence interval 1.35 to 1.99). Factors during the first year of life and currently that were significantly associated with wheeze were cooking with gas (odds ratio 2.04, 1.34 to 3.13), foam pillows (2.58, 1.66 to 3.99), and damp housing (1.89, 1.26 to 2.83). Factors protecting against wheeze were cotton quilts and the consumption of fruit and raw vegetables. CONCLUSION: Environmental factors and diet may explain the differences in prevalence of asthma between children living in different regions of China.

Asthma↗

Epidemiology of severe acute respiratory syndrome (SARS): adults and children.

Severe acute respiratory syndrome (SARS) is a newly described respiratory infection with pandemic potential. The causative agent is a new strain of coronavirus most likely originating from wild animals. This disease first emerged in November 2002 in Guangdong Province, China. Early in the outbreak the infection had been transmitted primarily via household contacts and healthcare settings. In late February 2003 the infection was transmitted to Hong Kong when an infected doctor from the mainland visited there. During his stay in Hong Kong at least 17 guests and visitors were infected at the hotel at which he stayed. By modern day air travel, the infection was rapidly spread to other countries including Vietnam, Singapore and Canada by these infected guests. With the implementation of effective control strategies including early isolation of suspected cases, strict infection control measures in the hospital setting, meticulous contact tracing and quarantine, the outbreak was finally brought under control by July 2003. In addition, there were another two events of SARS in China between the end of December 2003 and January 2004 and from March to May 2004; both were readily controlled without significant patient spread.

Adolescent↗

Outdoor air pollution and asthma.

PURPOSE OF REVIEW: The relation between outdoor air pollution and asthma has always been a major focus of research. The evidence that current levels of air pollution in many countries result in increased morbidity and mortality is fairly consistent. With rapid urbanization in many communities, traffic exhausts have become the major source of pollution, and many recent research studies have attempted to investigate the detrimental effects of this type of pollution. This paper reviews the recent evidence of the possible detrimental effects of ambient air pollution on the inception and morbidity of asthma. RECENT FINDINGS: Traffic related pollution has been confirmed in both cross-sectional and longitudinal studies to be associated with increased asthma morbidity and cardiopulmonary mortality. There is also evidence that pollutants such as ozone and traffic exhausts may be responsible for new incident cases of asthma. Among the particulate pollution, research investigating the ultrafine particles and the bacterial components suggested that these particles may have important role in asthma morbidity. SUMMARY: More research studies are needed to reveal how various air pollutants may interact with the host systems, such as the immune system, leading to increased morbidity in susceptible individuals. Reduction of the current levels of ambient air pollution should be an integral part of the overall effort in minimizing asthma morbidity or mortality in the community.

Air Pollutants↗