Association of the AhR, ARNT, and AhRR gene polymorphisms and cord blood AhR levels with elevated cord blood IgE susceptibility in Taiwan mother-infant pairs: a nested case-control study.

The roles of aryl hydrocarbon receptor (AhR), AhR-nuclear translocator (ARNT), and AhR repressor (AhRR) genes in the elevation of cord blood IgE (CbIgE) remained unclear. Our aims were to determine the polymorphisms of AhR, ARNT, and AhRR genes, cord blood AhR (CBAhR) level, and susceptibility to elevation of CbIgE. 206 infant-mother pairs with CbIgE>=0.35 IU/ml and 421 randomly selected controls recruited from our previous study. Genotyping was determined using TaqMan assays. Statistical analysis showed AhR rs2066853 (GG vs. AA+AG: adjusted OR (AOR)=1.5, 95%CI=1.10-2.31 and AOR=1.60, 95%CI=1.06-2.43, respectively) and the combination of AhR rs2066853 and maternal total IgE (mtIgE)>=100 IU/ml were significantly correlated with CbIgE>=0.35 IU/ml or CbIgE>=0.5 IU/ml. CBAhR in a random subsample and CbIgE levels were significantly higher in infants with rs2066853GG genotype. We suggest that infant AhR rs2066853 and their interactions with mtIgE>=100 IU/ml significantly correlate with elevated CbIgE, but AhRR and ARNT polymorphisms do not.

Interactive Effect of Diurnal Temperature Range and Temperature on Mortality, Northeast Asia.

BACKGROUND: The diurnal temperature range (DTR) represents temperature variability within a day and has been reported as a potential risk factor for mortality. Previous studies attempted to identify the role of temperature in the DTR-mortality association, but results are inconclusive. The aim of this study was to investigate the interactive effect of temperature and DTR on mortality using a multicountry time series analysis. METHODS: We collected time series data for mortality and weather variables for 57 communities of three countries (Taiwan, Korea, and Japan) in Northeast Asia (1972-2012). Two-stage time series regression with a distributed lag nonlinear model and meta-analysis was used to estimate the DTR-mortality association changing over temperature strata (six strata were defined based on community-specific temperature percentiles). We first investigated the whole population and then, the subpopulations defined by temperature distribution (cold and warm regions), sex, and age group (people <65 and ≥65 years of age), separately. RESULTS: The DTR-mortality association changed over temperature strata. The relative risk (RR) of mortality for 10°C increase in DTR was larger for high-temperature strata compared with cold-temperature strata (e.g., = 1.050; 95% confidence interval [CI] = 1.040, 1.060 at extreme-hot stratum and RR = 1.040; 95% CI = 1.031, 1.050 at extreme-cold stratum); extreme-hot and -cold strata were defined as the days with daily mean temperature above 90th and below 10th percentiles each community's temperature distribution. Such increasing pattern was more pronounced in cold region and in people who were 65 years or older. CONCLUSIONS: We found evidence that the DTR-related mortality may increase as temperature increases.

Synergic effect between high temperature and air pollution on mortality in Northeast Asia.

High temperature and air pollutants have been reported as potential risk factors of mortality. Previous studies investigated interaction between the two variables; however, the excess death risk due to the synergic effect (i.e. interaction on the additive scale) between the two variables has not been investigated adequately on a multi-country scale. This study aimed to assess the excess death risk due to the synergism between high temperature and air pollution on mortality using a multicity time-series analysis. We collected time-series data on mortality, weather variables, and four air pollutants (PM10, O3, NO2, and CO) for 16 metropolitan cities of three countries (Japan, Korea, and Taiwan) in Northeast Asia (1979-2015). Quasi-Poisson time-series regression and meta-analysis were used to estimate the additive interaction between high temperature and air pollution. The additive interaction was measured by relative excess risk due to interaction (RERI) index. We calculated RERI with relative risks (RR) of the 99th/10th, 90th/90th, and 99th/90th percentiles of temperature/air pollution metrics, where risk at the 90th/10th percentiles of temperature/air pollution metrics was the reference category. This study showed that there may exist positive and significant excess death risks due to the synergism between high temperature and air pollution in the total population for all pollutants (95% lower confidence intervals of all RERIs>0 or near 0). In final, we measured quantitatively the excess death risks due to synergic effect between high temperature and air pollution, and the synergism should be considered in public health interventions and a composite warning system.

Gestational diabetes mellitus was related to ambient air pollutant nitric oxide during early gestation.

BACKGROUND: Ambient air pollution has been linked to the risk of gestational diabetes mellitus (GDM). However, evidence of this association is limited, and no study has examined the effects of nitric oxide (NO). OBJECTIVE: This study investigated the association between air pollution exposure during gestation and GDM. METHODS: The Taiwan Birth Cohort Study database was used to examine the association between the risk of GDM and all routinely monitored air pollutants among 21,248 women who were pregnant during 2004-2005. We further employed a two-pollutant model for confirming the effect of each pollutant on GDM. RESULTS: After the exclusion criteria were applied, 19,606 women were included in the final analysis. Among them, 378 (1.9%) had been diagnosed as having GDM. These women were older and had higher BMIs than the women without GDM. The risks of GDM onset were significantly associated with NO exposure during the first [adjusted OR (aOR): 1.05, 95% confidence interval (CI): 1.02-1.08] and second (aOR: 1.05, 95%CI: 1.02-1.08) trimesters. Under the two-pollutant model, the effect of NO exposure was also significant during the first (aOR: 1.05, 95%CI: 1.02-1.08) and second (aOR: 1.05, 95%CI: 1.02-1.09) trimesters. CONCLUSION: The results indicated that exposure to higher NO levels during pregnancy increases the risk of GDM.

Mortality after exposure to polychlorinated biphenyls and dibenzofurans: 30 years after the "Yucheng accident".

BACKGROUND: In 1979, approximately 2,000 people in central Taiwan were accidentally exposed to polychlorinated biphenyls and dibenzofurans due to ingestion of contaminated cooking oil. This event was called Yucheng, "oil-syndrome" in Chinese. We followed the exposed persons and compared their cause-specific mortality with that of neighborhood referents 30 years after the accident. METHODS: We obtained age- and gender-matched referents from the 1979 neighborhoods of the exposed people. Cause-specific mortality was compared between exposed subjects (N=1803) and their neighborhood referents (N=5170) using standardized mortality ratios (SMR). Total person-years for the Yucheng subjects and neighborhood referents were 48,751 and 141,774, respectively. RESULTS: The SMR for all causes (SMR=1.2, 95% CI: 1.1-1.3), diseases of the circulatory system (SMR=1.3, 95% CI: 1.0-1.6), and diseases of the musculoskeletal system and connective tissue (SMR=6.4, 95% CI: 2.8-12.7) were elevated in Yucheng subjects. Among Yucheng males, the SMRs for diseases of the digestive system (SMR=1.9, 95% CI: 1.2-2.8), malignant neoplasm of stomach (SMR=3.5, 95% CI: 1.5-7.0), and malignant neoplasm of lymphatic and hematopoietic tissue (SMR=3.0, 95% CI: 1.1-6.6) were increased. The SMR for total neoplasms was increased (SMR=1.3, 95% CI: 0.9-1.7). CONCLUSION: We conclude that exposure to PCBs/PCDFs at levels that produced symptoms in many affects mortality patterns 3 decades after exposure.

Heat-related cardiorespiratory mortality: Effect modification by air pollution across 482 cities from 24 countries.

BACKGROUND: Evidence on the potential interactive effects of heat and ambient air pollution on cause-specific mortality is inconclusive and limited to selected locations. OBJECTIVES: We investigated the effects of heat on cardiovascular and respiratory mortality and its modification by air pollution during summer months (six consecutive hottest months) in 482 locations across 24 countries. METHODS: Location-specific daily death counts and exposure data (e.g., particulate matter with diameters ≤ 2.5 µm [PM2.5]) were obtained from 2000 to 2018. We used location-specific confounder-adjusted Quasi-Poisson regression with a tensor product between air temperature and the air pollutant. We extracted heat effects at low, medium, and high levels of pollutants, defined as the 5th, 50th, and 95th percentile of the location-specific pollutant concentrations. Country-specific and overall estimates were derived using a random-effects multilevel meta-analytical model. RESULTS: Heat was associated with increased cardiorespiratory mortality. Moreover, the heat effects were modified by elevated levels of all air pollutants in most locations, with stronger effects for respiratory than cardiovascular mortality. For example, the percent increase in respiratory mortality per increase in the 2-day average summer temperature from the 75th to the 99th percentile was 7.7% (95% Confidence Interval [CI] 7.6-7.7), 11.3% (95%CI 11.2-11.3), and 14.3% (95% CI 14.1-14.5) at low, medium, and high levels of PM2.5, respectively. Similarly, cardiovascular mortality increased by 1.6 (95%CI 1.5-1.6), 5.1 (95%CI 5.1-5.2), and 8.7 (95%CI 8.7-8.8) at low, medium, and high levels of O3, respectively. DISCUSSION: We observed considerable modification of the heat effects on cardiovascular and respiratory mortality by elevated levels of air pollutants. Therefore, mitigation measures following the new WHO Air Quality Guidelines are crucial to enhance better health and promote sustainable development.

A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children.

INTRODUCTION: Prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD). OBJECTIVES: Our aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children. METHODS: A total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL). RESULTS: Associations of maternal DEHP exposure (median 4.54µg/kg_bw/day) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) µg/kg_bw/dayfor an integrated CBCL score. CONCLUSIONS: The current TDI (RfD) of 50 (20) µg/kg_bw/day for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.

Longer-Term Impact of High and Low Temperature on Mortality: An International Study to Clarify Length of Mortality Displacement.

BACKGROUND: In many places, daily mortality has been shown to increase after days with particularly high or low temperatures, but such daily time-series studies cannot identify whether such increases reflect substantial life shortening or short-term displacement of deaths (harvesting). OBJECTIVES: To clarify this issue, we estimated the association between annual mortality and annual summaries of heat and cold in 278 locations from 12 countries. METHODS: Indices of annual heat and cold were used as predictors in regressions of annual mortality in each location, allowing for trends over time and clustering of annual count anomalies by country and pooling estimates using meta-regression. We used two indices of annual heat and cold based on preliminary standard daily analyses: a) mean annual degrees above/below minimum mortality temperature (MMT), and b) estimated fractions of deaths attributed to heat and cold. The first index was simpler and matched previous related research; the second was added because it allowed the interpretation that coefficients equal to 0 and 1 are consistent with none (0) or all (1) of the deaths attributable in daily analyses being displaced by at least 1 y. RESULTS: On average, regression coefficients of annual mortality on heat and cold mean degrees were 1.7% [95% confidence interval (CI): 0.3, 3.1] and 1.1% (95% CI: 0.6, 1.6) per degree, respectively, and daily attributable fractions were 0.8 (95% CI: 0.2, 1.3) and 1.1 (95% CI: 0.9, 1.4). The proximity of the latter coefficients to 1.0 provides evidence that most deaths found attributable to heat and cold in daily analyses were brought forward by at least 1 y. Estimates were broadly robust to alternative model assumptions. CONCLUSIONS: These results provide strong evidence that most deaths associated in daily analyses with heat and cold are displaced by at least 1 y. https://doi.org/10.1289/EHP1756.