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.

Fluctuating risk of acute kidney injury-related mortality for four weeks after exposure to air pollution: A multi-country time-series study in 6 countries.

BACKGROUND: Recent studies have reported that air pollution is related to kidney diseases. However, the global evidence on the risk of death from acute kidney injury (AKI) owing to air pollution is limited. Therefore, we investigated the association between short-term exposure to air pollution-particulate matter ≤ 2.5 µm (PM2.5), ozone (O3), and nitrogen dioxide (NO2)-and AKI-related mortality using a multi-country dataset. METHODS: This study included 41,379 AKI-related deaths in 136 locations in six countries during 1987-2018. A novel case time-series design was applied to each air pollutant during 0-28 lag days to estimate the association between air pollution and AKI-related deaths. Moreover, we calculated AKI deaths attributable to non-compliance with the World Health Organization (WHO) air quality guidelines. RESULTS: The relative risks (95% confidence interval) of AKI-related deaths are 1.052 (1.003, 1.103), 1.022 (0.994, 1.050), and 1.022 (0.982, 1.063) for 5, 10, and 10 µg/m3 increase in lag 0-28 days of PM2.5, warm-season O3, and NO2, respectively. The lag-distributed association showed that the risk appeared immediately on the day of exposure to air pollution, gradually decreased, and then increased again reaching the peak approximately 20 days after exposure to PM2.5 and O3. We also found that 1.9%, 6.3%, and 5.2% of AKI deaths were attributed to PM2.5, warm-season O3, and NO2 concentrations above the WHO guidelines. CONCLUSIONS: This study provides evidence that public health policies to reduce air pollution may alleviate the burden of death from AKI and suggests the need to investigate the several pathways between air pollution and AKI death.

Joint effect of heat and air pollution on mortality in 620 cities of 36 countries.

BACKGROUND: The epidemiological evidence on the interaction between heat and ambient air pollution on mortality is still inconsistent. OBJECTIVES: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries. METHODS: We used daily data on all-cause mortality, air temperature, particulate matter ≤ 10 µm (PM10), PM ≤ 2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) from 620 cities in 36 countries in the period 1995-2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants. RESULTS: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75th to the 99th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM10 was equal to 10 or 90 µg/m3, respectively. Corresponding estimates when daily O3 concentrations were 40 or 160 µg/m3 were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 µg/m3 increment in PM10 was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1st and 99th city-specific percentiles, respectively. Corresponding mortality estimate for O3 across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM2.5 and NO2. CONCLUSIONS: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities.

Air quality health index (AQHI) based on multiple air pollutants and mortality risks in Taiwan: Construction and validation.

The currently used air quality index (AQI) is not able to capture the additive effects of air pollution on health risks and reflect non-threshold concentration-response relationships, which has been criticized. We proposed the air quality health index (AQHI) based on daily air pollution-mortality associations, and compared its validity in predicting daily mortality and morbidity risks with the existing AQI. We examined the excess risk (ER) of daily elderly (≥65-year-old) mortality associated with 6 air pollutants (PM2.5, PM10, SO2, CO, NO2, and O3) in 72 townships across Taiwan from 2006 to 2014 by performing a time-series analysis using a Poisson regression model. Random effect meta-analysis was used to pool the township-specified ER for each air pollutant in the overall and seasonal scenarios. The integrated ERs for mortality were calculated and used to construct the AQHI. The association of the AQHI with daily mortality and morbidity were compared by calculating the percentage change per interquartile range (IQR) increase in the indices. The magnitude of the ER on the concentration-response curve was used to evaluate the performance of the AQHI and AQI, regarding specific health outcomes. Sensitivity analysis was conducted using coefficients from the single- and two-pollutant models. The coefficients of PM2.5, NO2, SO2, and O3 associated with mortality were included to form the overall and season-specific AQHI. An IQR increase in the overall AQHI at lag 0 was associated with 1.90%, 2.96%, and 2.68% increases in mortality, asthma, and respiratory outpatient visits, respectively. The AQHI had higher ERs for mortality and morbidity on the validity examinations than the current AQI. The AQHI, which captures the combined effects of air pollution, can serve as a health risk communication tool to the public.

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.

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.

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.

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.

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.

Gestational exposure to polychlorinated biphenyls and dibenzofurans induced asymmetric hearing loss: Yucheng children study.

INTRODUCTION: In 1979, approximately 2000 people in central Taiwan were exposed to polychlorinated biphenyls and dibenzofurans (PCBs/PCDFs) due to ingestion of contaminated rice oil. The children born to mothers exposed to PCBs/PCDFs were called Yucheng children. We conducted a follow-up study to examine the association between gestational PCBs/PCDFS exposure and auditory function in Yucheng children's early adulthood. METHODS: In 1985 and early 1992, Yucheng children and their age, gender, socio-economic matched unexposed referent children were recruited for physical examination and long-term follow-ups. In 2007, Yucheng children and referent children were invited to participate in a health examination, including assessment of pure-tone air-conduction thresholds and distortion product otoacoustic emissions (DPOAEs) test. Gestational exposure to PCBs/PCDFs in Yucheng children were estimated by back-extrapolation of their mother's serum concentration to the time of childbirth. RESULTS: A total of 86 Yucheng children (51.2% males) and 97 referent children (50.5% males) were included for analysis. No difference was found in demographic characteristics between two groups. Among the Yucheng children, 53 had estimated PCBs/PCDFs concentrations. We found that Yucheng children were at higher risk of having elevated hearing threshold at low frequencies in the right ear. Estimated maternal concentrations of 2,3,4,7,8-pnCDF at the time of birth were associated with increased hearing thresholds and decreased DPOAEs amplitudes at low frequencies in the right ear. CONCLUSION: Gestational exposure to PCBs/PCDFs caused adverse asymmetrical hearing effects detectable even in early adulthood.

Effects of particulate air pollution and ozone on lung function in non-asthmatic children.

INTRODUCTION: Information on the long-term effects of different air pollutant levels on lung function is relatively lacking in Asia and still inconclusive in the world. Age differential effects of air pollution are not known. OBJECTIVES: To assess the acute and subchronic effects of ambient air pollution on lung function and compared among children of different ages. METHODS: From April to May 2011, a nationwide study was conducted on schoolchildren aged 6-15 years in 44 schools of 24 districts in Taiwan. Spirograms were obtained from 1494 non-asthmatic children. Air pollution data were retrieved from air monitoring stations within one kilometre of the schools. Using three-level hierarchical linear models, individual lung function was fitted to air pollution, with adjustments for demographics, indoor exposures, outdoor activity, and districts. RESULTS: Lung function changes per inter-quartile increase of the past two-months average levels of particulate matter <2.5 µm (PM2.5) and ozone (12 µg/m(3), 32-44 and 6.7 ppb, 32-38, respectively) were -103 and -142 ml on FVC, -86 and -131 on FEV1, and -102 and -188 ml/s on MMEF, respectively. Lag-1-day ozone exposure was associated with decreased MMEF. In children aged 6-10, PM2.5 was associated with decreased FEV1/FVC and MMEF/FVC ratios. CONCLUSIONS: In children aged 6-15 years, sub-chronic exposure to ambient PM2.5 and ozone leads to reduced lung capacity, whereas acute exposure to ozone decreases mid-expiratory flow. In children aged 6-10 years, additional airway obstructive patterns in lung function may be associated with PM2.5 exposure.

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.