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1.  Bisphenol A Exposure and Asthma Development in School-Age Children: A Longitudinal Study 
PLoS ONE  2014;9(10):e111383.
Although the effect of bisphenol A on various health outcomes has been extensively examined, few studies have investigated its effect on asthma.
We hypothesized that exposure to bisphenol A in school-age children was associated with wheezing and asthma.
Participants included 127 children aged 7–8 years without a previous asthma diagnosis in an elementary school in Seoul, Korea. Three surveys were conducted, each 2 years apart. Bisphenol A concentration was measured at the baseline survey, and PC20, which is defined as the methacholine concentration that induces a decrease in FEV1 of 20% from baseline, was measured at every survey. Associations between bisphenol A concentration at 7–8 years of age and wheezing, asthma, and PC20 at ages up to 11–12 years were examined using generalized estimating equations, a marginal Cox regression model, and a linear mixed model.
The log-transformed creatinine-adjusted urinary bisphenol A concentration at 7–8 years was positively associated with wheezing (odds ratio, 2.48; 95% confidence interval, 1.15–5.31; P = .02) and asthma (hazard ratio, 2.13; 95% confidence interval, 1.51–3.00; P<.001) at ages up to 11–12 years. Bisphenol A was also negatively associated with PC20 (ß = −2.33; P = .02). When stratified by sex, the association between bisphenol A and asthma remained significant only in girls (hazard ratio, 2.45; 95% confidence interval, 2.18–2.76; P<.001).
Increased urinary bisphenol A concentrations at 7–8 years old were positively associated with wheezing and asthma and negatively associated with PC20 at ages up to 11–12 years.
PMCID: PMC4214730  PMID: 25356742
2.  Diethylhexyl Phthalates Is Associated with Insulin Resistance via Oxidative Stress in the Elderly: A Panel Study 
PLoS ONE  2013;8(8):e71392.
Insulin resistance (IR) is believed to be the underlying mechanism of metabolic syndrome and type 2 diabetes mellitus (DM). Recently, a few studies have demonstrated that phthalates could cause oxidative stress which would contribute to the development of IR. Therefore, we evaluated whether exposure to phthalates affects IR, and oxidative stress is involved in the phthalates-IR pathway.
We recruited 560 elderly participants, and obtained blood and urine samples during repeated medical examinations. For the determination of phthalate exposure, we measured urinary levels of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) as metabolites of diethylhexyl phthalates (DEHP), and mono-n-butyl phthalate (MnBP) as a metabolite of di-butyl phthalate (DBP). Malondialdehyde (MDA), an oxidative stress biomarker, was also measured in urine samples. We measured serum levels of fasting glucose and insulin, and derived the homeostatic model assessment (HOMA) index to assess IR. A mixed-effect model and penalized regression spline were used to estimate the associations among phthalate metabolites, MDA, and IR.
The molar sum of MEHHP and MEOHP (∑DEHP) were significantly associated with HOMA (β = 0.26, P = 0.040), and the association was apparent among participants with a history of DM (β = 0.88, P = 0.037) and among females (β = 0.30, P = 0.022). However, the relation between MnBP and HOMA was not found. When we evaluated whether oxidative stress is involved in increases of HOMA by ∑DEHP, MDA levels were significantly associated with increases of ∑DEHP (β = 0.11, P<0.001) and HOMA (β = 0.49, P = 0.049).
Our study results suggest that exposure to DEHP in the elderly population increases IR, which is related with oxidative stress, and that participants with a history of DM and females are more susceptible to DEHP exposure.
PMCID: PMC3747269  PMID: 23977034
3.  PM10 Exposure and Non-accidental Mortality in Asian Populations: A Meta-analysis of Time-series and Case-crossover Studies 
We investigated the association between particulate matter less than 10 µm in aerodynamic diameter (PM10) exposure and non-accidental mortality in Asian populations by meta-analysis, using both time-series and case-crossover analysis.
Among the 819 published studies searched from PubMed and EMBASE using key words related to PM10 exposure and non-accidental mortality in Asian countries, 8 time-series and 4 case-crossover studies were selected for meta-analysis after exclusion by selection criteria. We obtained the relative risk (RR) and 95% confidence intervals (CI) of non-accidental mortality per 10 µg/m3 increase of daily PM10 from each study. We used Q statistics to test the heterogeneity of the results among the different studies and evaluated for publication bias using Begg funnel plot and Egger test.
Testing for heterogeneity showed significance (p<0.001); thus, we applied a random-effects model. RR (95% CI) per 10 µg/m3 increase of daily PM10 for both the time-series and case-crossover studies combined, time-series studies relative risk only, and case-crossover studies only, were 1.0047 (1.0033 to 1.0062), 1.0057 (1.0029 to 1.0086), and 1.0027 (1.0010 to 1.0043), respectively. The non-significant Egger test suggested that this analysis was not likely to have a publication bias.
We found a significant positive association between PM10 exposure and non-accidental mortality among Asian populations. Continued investigations are encouraged to contribute to the health impact assessment and public health management of air pollution in Asian countries.
PMCID: PMC3567321  PMID: 23407325
PM10; Non-accidental mortality; Asia; Meta-analysis
4.  Air Pollution and Symptoms of Depression in Elderly Adults 
Environmental Health Perspectives  2012;120(7):1023-1028.
Background: Although the effect of air pollution on various diseases has been extensively investigated, few studies have examined its effect on depression.
Objectives: We investigated the effect of air pollution on symptoms of depression in an elderly population.
Methods: We enrolled 537 participants in the study who regularly visited a community center for the elderly located in Seoul, Korea. The Korean version of the Geriatric Depression Scale-Short Form (SGDS-K) was used to evaluate depressive symptomatology during a 3-year follow-up study. We associated ambient air pollutants with SGDS-K results using generalized estimating equations (GEE). We also conducted a factor analysis with items on the SGDS-K to determine which symptoms were associated with air pollution.
Results: SGDS-K scores were positively associated with interquartile range (IQR) increases in the 3-day moving average concentration of particulate matter with an aerodynamic diameter ≤ 10 μm (PM10) [17.0% increase in SGDS-K score, 95% confidence interval (CI): 4.9%, 30.5%], the 0–7 day moving average of nitrogen dioxide [NO2; 32.8% (95% CI: 12.6%, 56.6%)], and the 3-day moving average of ozone [O3; 43.7% (95% CI: 11.5%, 85.2%)]. For these three pollutants, factor analysis showed that air pollution was more strongly associated with emotional symptoms such as feeling happy and satisfied than with somatic or affective symptoms.
Conclusions: Our study suggests that increases in PM10, NO2, and O3 may increase depressive symptoms among the elderly. Of the symptoms evaluated, ambient air pollution was most strongly associated with emotional symptoms.
PMCID: PMC3404652  PMID: 22514209
air pollution; depressive symptoms; elderly; factor analysis; panel study
5.  Association of Serum 25-Hydroxyvitamin D Levels with Markers for Metabolic Syndrome in the Elderly: A Repeated Measure Analysis 
Journal of Korean Medical Science  2012;27(6):653-660.
The purpose of current study was to investigate associations of serum 25-hydroxyvitamin D (OHVD) levels with markers for metabolic syndrome in elderly Koreans. We conducted a panel study on 301 individuals over 60 yr old in Seoul, Korea, and repeatedly measured serum OHVD, glucose, insulin, and lipid levels. Mixed effect model and generalized estimating equations were used to investigate relationships between serum OHVD levels with marker levels for metabolic syndrome and each of its categories. Of all subjects, 76.6% were vitamin D deficient (< 50 nM) and 16.9% were insufficient (< 75 nM). Inverse association was demonstrated between serum OHVD levels and insulin (P = 0.004), triglyceride (P = 0.023) and blood pressure (systolic blood pressure: P = 0.002; diastolic blood pressure: P < 0.001). Vitamin D deficiency was found to increase risk of 'hypertriglyceridemia' category of metabolic syndrome (odds ratio: 1.73, 95% confidence interval: 1.13-2.66). In conclusion, we found from our repeated measure analysis that decreasing serum OHVD levels are associated with increasing insulin resistance, increasing serum triglyceride levels and increasing blood pressure in elderly Koreans, and confirmed on the risk of 'hypertriglyceridemia' in vitamin D deficient subjects.
PMCID: PMC3369452  PMID: 22690097
Vitamin D; Insulin Resistance; Metabolic Syndrome; Elderly; Mixed Effect Model
6.  Exposures to Particulate Matter and Polycyclic Aromatic Hydrocarbons and Oxidative Stress in Schoolchildren 
Environmental Health Perspectives  2009;118(4):579-583.
Air pollution is known to contribute to respiratory and cardiovascular mortality and morbidity. Oxidative stress has been suggested as one of the main mechanisms for these effects on health.
The aim of this study was to analyze the effects of exposure to particulate matter (PM) with aerodynamic diameters ≤ 10 μm (PM10) and ≤ 2.5 μm (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) on urinary malondialdehyde (MDA) levels in schoolchildren.
The study population consisted of 120 schoolchildren. The survey and measurements were conducted in four cities—two in China (Ala Shan and Beijing) and two in Korea (Jeju and Seoul)—between 4 and 9 June 2007. We measured daily ambient levels of PM and their metal components at the selected schools during the study period. We also measured urinary 1-hydroxypyrene (1-OHP) and 2-naphthol, to assess PAH exposure, and MDA, to assess oxidative stress. Measurements were conducted once a day for 5 consecutive days. We constructed a linear mixed model after adjusting for individual variables to estimate the effects of PM and PAH on oxidative stress.
We found statistically significant increases in urinary MDA levels with ambient PM concentrations from the current day to the 2 previous days (p < 0.0001). Urinary 1-OHP level also showed a positive association with urinary MDA level, which was statistically significant with or without PM in the model (p < 0.05). Outdoor PM and urinary 1-OHP were synergistically associated with urinary MDA levels. Some metals bound to PM10 (aluminum, iron, strontium, magnesium, silicon, arsenic, barium, zinc, copper, and cadmium) and PM2.5 (magnesium, iron, strontium, arsenic, cadmium, zinc, aluminum, mercury, barium, and copper) also had significant associations with urinary MDA level.
Exposure to PM air pollution and PAHs was associated with oxidative stress in schoolchildren.
PMCID: PMC2854738  PMID: 20368125
children; metal; oxidative stress; PAH; panel study; particulate matter

Results 1-6 (6)