Ju-Hee Seo

Maternal exposure to particulate air pollution and term birth weight : a multi-country evaluation of effect and heterogeneity

Background: A growing body of evidence has associated maternal exposure to air pollution with adverse effects on fetal growth; however, the existing literature is inconsistent. Objectives: We aimed to quantify the association between maternal exposure to particulate air pollution and term birth weight and low birth weight (LBW) across 14 centers from 9 countries, and to explore the influence of site characteristics and exposure assessment methods on between-center heterogeneity in this association. Methods: Using a common analytical protocol, International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) centers generated effect estimates for term LBW and continuous birth weight associated with PM10 and PM2.5 (particulate matter ≤ 10 and 2.5 µm). We used meta-analysis to combine the estimates of effect across centers (~ 3 million births) and used meta-regression to evaluate the influence of center characteristics and exposure assessment methods on between-center heterogeneity in reported effect estimates. Results: In random-effects meta-analyses, term LBW was positively associated with a 10-μg/m3 increase in PM10 [odds ratio (OR) = 1.03; 95% CI: 1.01, 1.05] and PM2.5 (OR = 1.10; 95% CI: 1.03, 1.18) exposure during the entire pregnancy, adjusted for maternal socioeconomic status. A 10-μg/m3 increase in PM10 exposure was also negatively associated with term birth weight as a continuous outcome in the fully adjusted random-effects meta-analyses (–8.9 g; 95% CI: –13.2, –4.6 g). Meta-regressions revealed that centers with higher median PM2.5 levels and PM2.5:PM10 ratios, and centers that used a temporal exposure assessment (compared with spatiotemporal), tended to report stronger associations. Conclusion: Maternal exposure to particulate pollution was associated with LBW at term across study populations. We detected three site characteristics and aspects of exposure assessment methodology that appeared to contribute to the variation in associations reported by centers.

Asthma Prevention by Lactobacillus Rhamnosus in a Mouse Model is Associated With CD4+CD25+Foxp3+ T Cells

Purpose Probiotic bacteria can induce immune regulation or immune tolerance in allergic diseases. The underlying mechanisms have been recently investigated, but are still unclear. The aim of this study was to evaluate the protective effects of the probiotic Lactobacillus rhamnosus (Lcr35) in a mouse model of asthma and to identify its mechanism of action. Methods Lcr35 was administered daily by the oral route at a dosage of 1×109 CFU/mouse in BALB/c mice for 7 days before the first sensitization. Clinical parameters and regulatory T (Treg) cells were examined. The role of CD4+CD25+Foxp3+ Treg cells was analyzed using a Treg cell-depleting anti-CD25 monoclonal antibody (mAb). Results Airway hyperresponsiveness, total IgE production, pulmonary eosinophilic inflammation, and splenic lymphocyte proliferation were suppressed after Lcr35 treatment. Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokines in the serum were suppressed, and the percentage of CD4+CD25+Foxp3+ Treg cells in the spleen was significantly increased in the Lcr35 treatment group. Anti-CD25 mAb administration abolished the protective effects of Lcr35, indicating that CD4+ CD25+Foxp3+ Treg cells are essential in mediating the activity of Lcr35. Conclusions Oral administration of Lcr35 attenuated the features of allergic asthma in a mouse model and induced immune regulation by a CD4+CD25+Foxp3+ Treg cell-mediated mechanism.

Association of ozone exposure with asthma, allergic rhinitis, and allergic sensitization

BACKGROUND Children are vulnerable to air pollution, which is known to be related to the recent increasing trend of allergic disease. OBJECTIVE To investigate the effects of air pollution on respiratory allergic diseases in school children. METHODS A prospective survey of parental responses to International Study of Asthma and Allergies in Childhood questionnaires, together with allergy evaluation, was conducted in 1743 school children selected from metropolitan cities and industrial areas during a 2-year period. Individual exposure to air pollution was estimated by using a geometric information system with the 5-year mean concentration of air pollutants. RESULTS A total of 1,340 children (male:female ratio, 51.4:48.6) with a mean (SD) age of 6.84 (0.51) years were included in the analysis. Each child underwent allergy evaluation at the time of enrollment and at a 2-year follow-up. After 2 years, the 12-month prevalence of wheezing was significantly decreased, whereas the lifetime prevalence of allergic rhinitis showed a significant increase. Ozone exposure was significantly associated with the 12-month prevalence of wheeze (odds ratio per 5 ppb, 1.372; 95% confidence interval, 1.016-1.852). Ozone was also associated with allergic rhinitis in children who reside in industrial areas. In addition, significant positive associations between ozone and the rate of newly developed sensitization to outdoor allergen were found (P for trend = .007). CONCLUSION Exposure to ozone was associated with current wheeze and allergic rhinitis. An increased rate of newly developed sensitization to outdoor allergen by ozone may explain the association.

The International Collaboration on Air Pollution and Pregnancy Outcomes: initial results.

Background: The findings of prior studies of air pollution effects on adverse birth outcomes are difficult to synthesize because of differences in study design. Objectives: The International Collaboration on Air Pollution and Pregnancy Outcomes was formed to understand how differences in research methods contribute to variations in findings. We initiated a feasibility study to a) assess the ability of geographically diverse research groups to analyze their data sets using a common protocol and b) perform location-specific analyses of air pollution effects on birth weight using a standardized statistical approach. Methods: Fourteen research groups from nine countries participated. We developed a protocol to estimate odds ratios (ORs) for the association between particulate matter ≤ 10 μm in aerodynamic diameter (PM10) and low birth weight (LBW) among term births, adjusted first for socioeconomic status (SES) and second for additional location-specific variables. Results: Among locations with data for the PM10 analysis, ORs estimating the relative risk of term LBW associated with a 10-μg/m3 increase in average PM10 concentration during pregnancy, adjusted for SES, ranged from 0.63 [95% confidence interval (CI), 0.30–1.35] for the Netherlands to 1.15 (95% CI, 0.61–2.18) for Vancouver, with six research groups reporting statistically significant adverse associations. We found evidence of statistically significant heterogeneity in estimated effects among locations. Conclusions: Variability in PM10–LBW relationships among study locations remained despite use of a common statistical approach. A more detailed meta-analysis and use of more complex protocols for future analysis may uncover reasons for heterogeneity across locations. However, our findings confirm the potential for a diverse group of researchers to analyze their data in a standardized way to improve understanding of air pollution effects on birth outcomes.

Prevalence of Atopy and Allergic Diseases in Korean Children: Associations with a Farming Environment and Rural Lifestyle

Background: The results of recent studies suggest that factors in rural environments may protect against the development of allergic diseases, but the underlying mechanisms are not well understood. The aim of this study was to investigate the prevalence of allergic diseases, to establish if this prevalence is influenced by migration from rural to urban areas and to identify environmental risk factors associated with these diseases. Methods: A cross-sectional study of children aged 9–12 years from a rural village, a rural town and an urban city in Korea was conducted. Demographic and disease-related information was obtained via a detailed questionnaire, and skin prick tests were performed. Results: There were significant differences in lifestyle and environmental factors between children from the rural village, the rural town and the urban children. The prevalence of allergic diseases and atopy was higher in urban children. A lower prevalence of allergic diseases and atopy was associated with farming parents, contact with farm animals during pregnancy, owning pets or a stable, breast-feeding and having older siblings. A comparison of rural village and rural town children revealed no evidence of an association of allergic diseases and atopy with farming parents, contact with farm animals during pregnancy or owning a stable. On the other hand, having older siblings and antibiotic use during infancy were significantly associated with allergic diseases and atopy in these children. Conclusions: Protective factors associated with a farming environment and/or rural lifestyle may influence the prevalence of allergic diseases and atopy in Korean children.

Interaction between IL13 genotype and environmental factors in the risk for allergic rhinitis in Korean children

BACKGROUND The prevalence of allergic rhinitis (AR) is increasing worldwide. Allergic diseases develop in susceptible subjects when they are exposed to specific environmental factors. OBJECTIVE We analyzed changes in the prevalence of AR and identified genetic and environmental factors in early childhood that affect risk. METHODS We used the International Study of Asthma and Allergies in Childhood questionnaire to collect data on AR, allergies, and environmental exposures from 4554 elementary school students from 5 areas of Seoul, Korea, in 2008. We also obtained DNA from 1050 subjects from 1 area of Seoul for genotype analysis of IL13. RESULTS We identified genetic and environmental factors during infancy and early childhood that increased the risk for current AR (resulting in a diagnosis of AR and AR symptoms in the past 12 months) in elementary school-aged children. These included allergic disease in parents and antibiotic use in infants, allergic disease in parents and exposure of infants to mold, and allergic disease in parents and moving an infant to a newly built house. The risk of current AR also increased in subjects with GA or AA at nucleotide 2044 in IL13 who had been exposed to mold in the home during infancy (adjusted odds ratio, 3.27; 95% CI, 1.75-6.11) compared with subjects who had GG at this position and had not been exposed to mold (adjusted odds ratio, 3.27; 95% CI, 1.75-6.11). CONCLUSION The prevalence of AR is increasing in Korean children. Children with a family history of allergic disease and exposure to specific environmental risk factors during infancy are more likely to have AR. Children with GA or AA at IL13(+2044) are at increased risk for AR when exposed to mold in the home during the first year of life.

Korean Environmental Health Survey in Children and Adolescents (KorEHS-C): Survey design and pilot study results on selected exposure biomarkers

For the first nationwide representative survey on the environmental health of children and adolescents in Korea, we designed the Korean Environmental Health Survey in Children and Adolescents (KorEHS-C) as a two-phase survey and planned a sampling strategy that would represent the whole population of Korean children and adolescents, based on the school unit for the 6-19 years age group and the household unit for the 5 years or less age group. A pilot study for 351 children and adolescents aged 6 to 19 years in elementary, middle, and high school of two cities was performed to validate several measurement methods and tools, as well as to test their feasibility, and to elaborate the protocols used throughout the survey process. Selected exposure biomarkers, i.e., lead, mercury, cadmium in blood, and bisphenol A, metabolites of diethylhexyl phthalate and di-n-butyl phthalate and cotinine in urine were analyzed. We found that the levels of blood mercury (Median: 1.7 ug/L) and cadmium (Median: 0.30 ug/L) were much higher than those of subjects in Germany and the US, while metabolites of phthalates and bisphenol A showed similar levels and tendencies by age; the highest levels of phthalate metabolites and bisphenol A occurred in the youngest group of children. Specific investigations to elucidate the exposure pathways of major environmental exposure need to be conducted, and the KorEHS-C should cover as many potential environmental hazards as possible.

Exposure to Gene-Environment Interactions before 1 Year of Age May Favor the Development of Atopic Dermatitis

Background: The aims of this study were to determine (1) the prevalence of atopic dermatitis (AD) in Seoul, Korea, and (2) the influence of environmental and genetic factors on disease risk. Methods: A questionnaire survey was conducted in 5,036 primary school children and 4,607 middle school children in 2008. For each child, a modified version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and a questionnaire assessing exposure to environmental variables were completed. Results: In primary school children, the lifetime prevalence of itchy eczema was 24.3%, the 12-month prevalence of itchy flexural eczema was 18.0%, the lifetime prevalence of AD diagnosis was 31.3%, and the 12-month prevalence of AD treatment was 14.5%. In middle school children, the corresponding rates were 16.0, 10.8, 22.1, and 8.3%, respectively. These rates are significantly higher than those reported in similar studies conducted in 1995 and 2000. In both primary and middle school children, a parental history of allergic disease and a history of having moved into a newly built house before 1 year of age were independently associated with a risk for current AD. For current AD, the prevalence odds ratio was higher in the subgroup with both a genetic and a specific environmental risk factor than in the subgroup with no risk factor or subgroups with only one risk factor. Conclusions: The prevalence of AD in primary and middle school children in Seoul has increased. Its development may be influenced by gene-environment interactions, particularly before 1 year of age.

Clinical efficacy and mechanism of probiotics in allergic diseases

A complex interplay between genetic and environmental factors partially contributes to the development of allergic diseases by affecting development during prenatal and early life. To explain the dramatic increase in the prevalence of allergic diseases, the hygiene hypothesis proposed that early exposure to infection prevented allergic diseases. The hygiene hypothesis has changed to the microbial hypothesis, in which exposure to microbes is closely linked to the development of the early immune system and allergic diseases. The intestinal flora may contribute to allergic disease through its substantial effect on mucosal immunity. Based on findings that exposure to microbial flora early in life can change the Th1/Th2 balance, thus favoring a Th1 cell response, probiotics may be beneficial in preventing allergic diseases. However, evidence from clinical and basic research to prove the efficacy of probiotics in preventing allergy is lacking. To date, studies have yielded inconsistent findings on the usefulness of probiotics in allergic diseases. It is difficult to demonstrate an exact effect of probiotics on asthma, allergic rhinitis, and food allergy because of study limitations, such as different first supplementation period, duration, different strains, short follow-up period, and host factors. However, many studies have demonstrated a significant clinical improvement in atopic dermatitis with the use of probiotics. An accurate understanding of the development of human immunity, intestinal barrier function, intestinal microbiota, and systemic immunity is required to comprehend the effects of probiotics on allergic diseases.

GSDMB/ORMDL3 variants contribute to asthma susceptibility and eosinophil-mediated bronchial hyperresponsiveness

In 2007, a genome-wide association study identified associations between variants involved in the regulation of ORMDL3 expression and asthma. These observations were subsequently replicated in case-control studies in several ethnic groups. We investigated the possible contribution of GSDMB/ORMDL3 variants to asthma susceptibility and intermediate asthma phenotypes in Korean children. The polymorphisms rs7216389, rs4794820, rs4065275, and rs11650680 were genotyped using the TaqMan assay in 931 asthmatics and 480 normal controls in a case-control study, and in 1907 elementary school children in a general population study. Each subject also underwent peripheral blood analysis of immunoglobulin E levels, eosinophil cationic protein (ECP) levels, and eosinophil percentage. Pulmonary function testing (FEV(1) and MMEF) and a methacholine provocation test (PC(20)) were also performed. The case-control study revealed a significant association between a linkage disequilibrium block, including rs7216389, rs4794820, and rs4065275, and susceptibility to asthma and atopic asthma. The CT and TT genotypes of rs11650680 were associated with lower logECP levels than the CC genotype in asthmatics, while the GA and AA genotypes of rs4794820 were associated with higher logPC(20) values than the GG genotype in atopic asthmatics. The haplotype (CAA) of rs7216389, rs4794820 and rs4065275 was associated with a lower risk of asthma susceptibility and a higher logPC(20). In the general population study, rs11650680 was significantly associated with a diagnosis of asthma. Moreover, the GA and AA genotypes of rs4794820 were associated with higher logPC(20) values and lower eosinophil percentages than the GG genotype in subjects who had been diagnosed with asthma, or showed bronchial hyperresponsiveness (PC(20)≤16). The GSDMB/ORMDL3 gene block, which includes rs7216389, rs4065275, rs4794820, and rs11650680, may be associated with asthma susceptibility in Korean children because it promotes eosinophilic inflammation, which induces bronchial hyperresponsiveness.