Acute Bronchitis and Bronchiolitis Infection in Children with Asthma and Allergic Rhinitis: A Retrospective Cohort Study Based on 5,027,486 Children in Taiwan.

This study evaluated the risks of childhood acute bronchitis and bronchiolitis (CABs) for children with asthma or allergic rhinitis (AR). Using insurance claims data of Taiwan, we identified, from children of ≤12 years old in 2000-2016, cohorts with and without asthma (N = 192,126, each) and cohorts with and without AR (N = 1,062,903, each) matched by sex and age. By the end of 2016, the asthma cohort had the highest bronchitis incidence, AR and non-asthma cohorts followed, and the lowest in the non-AR cohort (525.1, 322.4, 236.0 and 169.9 per 1000 person-years, respectively). The Cox method estimated adjusted hazard ratios (aHRs) of bronchitis were 1.82 (95% confidence interval (CI), 1.80-1.83) for the asthma cohort and 1.68 (95% CI, 1.68-1.69) for the AR cohort, relative to the respective comparisons. The bronchiolitis incidence rates for these cohorts were 42.7, 29.5, 28.5 and 20.1 per 1000 person-years, respectively. The aHRs of bronchiolitis were 1.50 (95% CI, 1.48-1.52) for the asthma cohort and 1.46 (95% CI, 1.45-1.47) for the AR cohort relative to their comparisons. The CABs incidence rates decreased substantially with increasing age, but were relatively similar for boys and girls. In conclusion, children with asthma are more likely to develop CABs than are children with AR.

Roles of Ambient Temperature and PM2.5 on Childhood Acute Bronchitis and Bronchiolitis from Viral Infection.

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006−2016. The monthly average incident CABs increased with increasing PM2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June−August). The highest incidence was 698 cases/day at <20 °C with PM2.5 > 37.0 µg/m3, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97−1.04) compared to 568 cases/day at <20 °C with PM2.5 < 15.0 µg/m3 (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85−1.06) with PM2.5 > 37.0 µg/m3 and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58−0.65) when PM2.5 was <15.0 µg/m3. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM2.5 concentrations, and the high PM2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM2.5 and CABs.

Childhood Rotavirus Infection Associated with Temperature and Particulate Matter 2.5 µm: A Retrospective Cohort Study.

No study has ever investigated how ambient temperature and PM2.5 mediate rotavirus infection (RvI) in children. We used insurance claims data from Taiwan in 2006-2012 to evaluate the RvI characteristics in children aged ≤ 9. The RvI incidence rates were higher in colder months, reaching the highest in March (117.0/100 days), and then declining to the lowest in July (29.2/100 days). The age-sex-specific average incident cases were all higher in boys than in girls. Stratified analysis by temperature (<20, 20-24, and ≥25 °C) and PM2.5 (<17.5, 17.5-31.4, 31.5-41.9, and ≥42.0 µg/m3) showed that the highest incidence was 16.4/100 days at average temperatures of <20 °C and PM2.5 of 31.5-41.9 µg/m3, with Poisson regression analysis estimating an adjusted relative risk (aRR) of 1.26 (95% confidence interval (CI) = 1.11-1.43), compared to the incidence at the reference condition (<20 °C and PM2.5 < 17.5 µg/m3). As the temperature increased, the incident RvI cases reduced to 4.84 cases/100 days (aRR = 0.40, 95% CI = 0.35-0.45) when it was >25 °C with PM2.5 < 17.5 µg/m3, or to 9.84/100 days (aRR = 0.81, 95% CI = 0.77-0.93) when it was >25 °C with PM2.5 > 42 µg/m3. The seasonal RvI is associated with frequent indoor personal contact among children in the cold months. The association with PM2.5 could be an alternative assessment due to temperature inversion.

Assessing Risk-Based Upper Limits of Melamine Migration from Food Containers.

Melamine contamination of food has become a major food safety issue because of incidents of infant disease caused by exposure to this chemical. This study was aimed at establishing a safety limit in Taiwan for the degree of melamine migration from food containers. Health risk assessment was performed for three exposure groups (preschool children, individuals who dine out, and elderly residents of nursing homes). Selected values of tolerable daily intake (TDI) for melamine were used to calculate the reference migration concentration limit (RMCL) or reference specific migration limit (RSML) for melamine food containers. The only existing values of these limits for international standards today are 1.2 mg/L (0.2 mg/dm2 ) in China and 30 mg/L (5 mg/dm2 ) in the European Union. The factors used in the calculations included the specific surface area of food containers, daily food consumption rate, body weight, TDI, and the percentile of the population protected at a given migration concentration limit (MCL). The results indicate that children are indeed at higher risk of melamine exposure at toxic levels than are other groups and that the 95th percentile of MCL (specific surface area = 5) for children aged 1-6 years should be the RMCL (0.07 mg/dm2 ) for protecting the sensitive and general population.

Food safety risk assessment for estimating dietary intake of sulfites in the Taiwanese population.

The purpose of this study was to assess the health risk associated with dietary intake of sulfites for Taiwanese general consumers by conducting a total diet study (TDS). We evaluated the exposure of Taiwanese to sulfites in the diet and its associated health risk. This study used a list of 128 food items representing 83% of the total daily diet. Among the 128 food items, 59 items may contain sulfites. Samples of the 59 food items were collected and subjected to chemical analysis to determine the sulfur dioxide concentration. Health risk was assessed by calculating the ratio of exposure level to the acceptable daily intake (ADI) level of the analyte. For high-intake consumers, the HI of sulfites was 19.7% ADI for males over the age of three years at the 95th percentile; whereas for females over the age of 66, the HI was 17.8% ADI. The HI for high-intake consumers was above 10% ADI. This suggests that regulatory actions must be continued and that consumers should be advised to be aware of processed foods with relatively high contamination to avoid excessive exposure.

Dietary exposure estimates for the food preservatives benzoic acid and sorbic acid in the total diet in Taiwan.

The purpose was to assess the health risk to general consumers in Taiwan associated with dietary intake of benzoic acid and sorbic acid by conducting a total diet study (TDS). The hazard index (HI) in percent acceptable daily intake (%ADI) of benzoic acid and sorbic acid for eight exposure groups classified by age were calculated. In high-intake consumers, the highest HI of benzoic acid was 54.1%ADI for males aged 1-2 years old at the 95th percentile, whereas for females, the HI was 61.7%ADI for aged over 66 years old. The highest HI of sorbic acid for male and female consumers aged 3-6 years old at the 95th percentile were 14.0%ADI and 12.2%ADI, respectively. These results indicate that the use of benzoic acid and sorbic acid as preservatives at the current level of use in the Taiwanese diet does not constitute a public health and safety concern.

High serum iron is associated with increased cancer risk.

Epidemiologic studies linking high serum iron with cancer risks are limited and inconclusive, despite evidence implicating body iron in human carcinogenesis. A cohort of 309,443 adults in Taiwan who had no history of cancer had serum iron levels tested at the time of recruitment (1997-2008). Initially measured iron levels were associated with subsequent cancer risk by linking individuals with the National Cancer Registry and National Death File. HRs were calculated by the Cox model. One third of males (35%) and one fifth of females (18%) had high serum iron (≥120 µg/dL), which was associated with a 25% increase in risk for incidence of all cancers [HR, 1.25; 95% confidence interval (CI), 1.16-1.35] and with a 39% increase in risk for mortality from all cancers (HR, 1.39; 95% CI, 1.23-1.57). The relationship between serum iron and cancer risk was a J-shaped one, with higher cancer risk at both ends, either at lower than 60 µg/dL or higher than 120 µg/dL. At the higher end, cancer risk increased by 4% for every 10 µg/dL increment above 80 µg/dL, showing a dose-response relationship, with 60 to 79 µg/dL as a reference level. In a sensitivity analysis, the increases in risk were still observed after the first 5 years of cancer cases were excluded. Liver cancer risk was increased in HBV (-) non-hepatitis B carrier (3-fold) and HBV (+) hepatitis B carrier (24-fold). Lifestyle risks such as smoking, drinking, or inactivity interacted synergistically with high serum iron and significantly increased the cancer risks. The liver (HR, 2.49; 95% CI, 1.97-3.16) and the breast (HR, 1.31; 95% CI, 1.01-1.70) were the two major cancer sites where significant cancer risks were observed for serum iron either ≥120 µg/dL or ≥140 µg/dL, respectively. This study reveals that high serum iron is both a common disorder and a marker of increased risk for several cancers.

ERα phenotype, estrogen level, and benzo[a]pyrene exposure modulate tumor growth and metabolism of lung adenocarcinoma cells.

Women have a higher risk of lung adenocarcinoma than men, suggesting that estrogen pathway may be involved in the pathogenesis of this cancer. This study was designed to determine whether ERα expression, estrogen levels, and endocrine disruptor exposure would influence tumor growth of lung adenocarcinoma cells using a xenograft model in which human lung adenocarcinoma cells with and without transgenic ERα expression were transplanted into female nude mice. Results showed that estrogen promoted tumor growth of ERα(+) lung adenocarcinoma cells but inhibited that of ERα(-) lung adenocarcinoma cells. Endocrine disruptor benzo[a]pyrene stimulated ERα(-) tumor growth dose dependently. Either of ovariectomy and ERα expression abolished the tumor growth-promoting effect of benzo[a]pyrene. The high CYP1B1/CYP1A1 and low COMT/CYP1B1 expression ratios detected in ERα(+) tumors suggested an accumulation of 4-hydroxyestradiol metabolite under high body estrogen, whereas comparable CYP1A1 and CYP1B1 expression plus estrogen-inducible COMT expression might favor the formation of 2-methoxyestradiol in ERα(-) tumors. Inhibition of estrogen on ERα(-) tumor growth might be partly attributable to the anti-proliferative action of 2-methoxyestradiol. Benzo[a]pyrene increased expression of CYP1B1 over CYP1A1 and suppressed estrogen-induced COMT up-regulation in ERα(-) tumor cells, probably switching estrogen metabolism to 4-hydroxyestradiol formation and removing the inhibition of 2-methoxyestradiol on ERα(-) tumors. ERα inhibited AhR from up-regulating CYP1 in response to benzo[a]pyrene exposure, but it increased angiogenic VEGF-A expression with body estrogen levels. Estrogen might increase ERα(+) lung adenocarcinoma growth by up-regulating cancer-related ERα target gene expression.

A GIS-aided assessment of the health hazards of cadmium in farm soils in central Taiwan.

A geostatistical method was developed to examine the correlation, or lack of it, between the levels of cadmium (Cd) detected in farm soils and those detected in the human specimens collected from residents around the contaminated areas in Changhua County where cadmium contamination of staple rice has been documented. We used the Taiwan EPA environment data in 2002 and human data which were generated by the National Health Research Institutes during 2003-2005. Kriging interpolation methods were used to determine soil Cd concentrations. A Zonal statistical function was performed to assess the individual exposure. Soil Cd levels and tissue Cd levels in residents were analyzed for contamination hotspots and other areas to determine correlation between the two variables. Three Cd contamination hotspots were identified, in which no correlation was found between soil Cd levels and tissue Cd levels in residents. Our results demonstrate how GIS spatial modeling technique can be used to estimate distribution of pollutants in an area using a limited number of data points. Results indicated no association between the soil contamination and the exposure of residents to Cd, suggesting that both the soils and the residents are receptors of Cd as a pollutant from as yet unidentified sources.

Polycyclic aromatic hydrocarbons in cigarette sidestream smoke particulates from a Taiwanese brand and their carcinogenic relevance.

Polycyclic aromatic hydrocarbons (PAHs) adsorbed on cigarette sidestream smoke particulates (CSSPs) have been regarded as important contributors to lung carcinogenesis in never smokers. However, limited information is available on PAH levels in cigarette sidestream smoke. Here we determine the concentrations of 22 PAHs, including 16 US EPA priority PAHs, in CSSPs generated from a high market-share domestic brand in Taiwan. Five of the 22 PAHs are undetectable. The remaining 17 PAHs constitute about 0.022% of the total mass of CSSPs. Near one fifth of the PAH mass come from IARC group 1 and group 2 carcinogens. Carcinogenic potency is equivalent to 144 ng benzo[a]pyrene per cigarette converted according to potency equivalency factors (PEFs). The CSSP condensate could activate AhR activity and induce AhR target gene expression. High concentrations of CSSPs also exhibited AhR-independent cytotoxicity. However, mixing the 17 PAHs as the composition in the CSSP condensate could not reconstitute either capacity. Since AhR activation and cytotoxicity are important mechanisms underlying carcinogenic potency, the results suggest that other component compounds play a more active role in carcinogenesis. The approach of individual PAH profiling plus PEF conversion commonly used in risk assessment is likely to underestimate the risk caused by environmental cigarette smoke exposure.

Population physiologically based pharmacokinetic modeling for the human lactational transfer of PCB-153 with consideration of worldwide human biomonitoring results.

BACKGROUND: One of the most serious human health concerns related to environmental contamination with polychlorinated biphenyls (PCBs) is the presence of these chemicals in breast milk. OBJECTIVES: We developed a physiologically based pharmacokinetic model of PCB-153 in women, and predict its transfer via lactation to infants. The model is the first human, population-scale lactational model for PCB-153. Data in the literature provided estimates for model development and for performance assessment. METHODS: We used physiologic parameters from a cohort in Taiwan and reference values given in the literature to estimate partition coefficients based on chemical structure and the lipid content in various body tissues. Using exposure data from Japan, we predicted acquired body burden of PCB-153 at an average childbearing age of 25 years and compared predictions to measurements from studies in multiple countries. We attempted one example of reverse dosimetry modeling using our PBPK model for possible exposure scenarios in Canadian Inuits, the population with the highest breast milk PCB-153 level in the world. RESULTS: Forward-model predictions agree well with human biomonitoring measurements, as represented by summary statistics and uncertainty estimates. CONCLUSION: The model successfully describes the range of possible PCB-153 dispositions in maternal milk, suggesting a promising option for back-estimating doses for various populations.

PM2.5 and associated polycyclic aromatic hydrocarbon and mutagenicity emissions from motorcycles.

In this study, PM(2.5) in diluted exhausts of motorcycles are collected and emission characteristics of PM(2.5)-associated polycyclic aromatic hydrocarbons (PAHs) and mutagenicities are investigated. The measured mutagenicity emission factors with metabolic activation for new fuel injection, used fuel injection, new carburetor and used carburetor motorcycles are 7.77 x 10(4), 1.18 x 10(5), 1.32 x 10(5) and 1.15 x 10(5) rev/km, respectively. The mutagenicity emission factors with metabolic activation are higher than the corresponding values without metabolic activation. The average PAH emission factors are 12.3, 16.3, 25.5 and 26.5 microg/km for new and used fuel-injection motorcycles, and new and used carburetor-operated motorcycles, respectively. The correlation coefficients between PAHs and mutagenicity emission factors are higher with metabolic activation (0.59) than that without metabolic activation (0.31).

Inorganic arsenic exposure and its relation to metabolic syndrome in an industrial area of Taiwan.

Past arsenic exposure was found associated with increased incidence of type 2 diabetes. However, the mechanisms remain unclear. Metabolic syndrome has been shown as a strong predictor for diabetes occurrence. We aimed at examining the association of inorganic arsenic exposure and the prevalence of metabolic syndrome. The authors recruited 660 age and gender stratified random population of residents in central Taiwan during 2002-2003. They received home interviews and health examinations at local health care units, where blood and hair specimens were collected. Hair arsenic (H-As) concentrations were determined by inductively coupled plasma-mass spectrometry. Metabolic syndrome was defined as the presence of three or more of the following risk factors: elevated levels of blood pressure, plasma glucose, and triglycerides, also the body mass index, and reduced high-density lipoprotein. Prevalence of metabolic syndrome increased from the 2nd tertile (0.034 ug/g) of H-As levels (odds ratio=2.54, 95% confidence interval: 1.20-5.39, p=0.015) after the adjustment for age, gender, occupation and life styles including cigarette smoking. We further found linear relation between H-As concentrations and increased levels of plasma glucose and lipids, and blood pressures. This first report may help identify modifiable factors associated with diabetogenesis and cardiovascular disease progression and thus be worth following for community health.

Survey of urinary nickel in residents of areas with a high density of electroplating factories.

The soil metal contamination arising from the discharge of the high density of electroplating factories in the geographic center of Taiwan has prompted concern about human exposure to harmful metals. This study aimed to determine the levels of nickel (Ni) in urine of residents living in the high vs. low factory-density areas, and to examine how these levels relate to gender and age. A total of 660 subjects, resident in the area for the last five years, were sampled according to the stratified random sampling approach, at ages 35-44, 45-54, and 55-64years for both genders. Metals in urine samples were analyzed by inductively coupled plasma mass spectrometry (ICPMS). The geometric mean (95% confidence interval (CI)) of urinary Ni was 6.30 (5.99-6.62)mug/l. The 0.95 parametric reference interval (90% CI) of urinary Ni was estimated to be 1.74 (1.62-1.88) to 22.73 (21.14-24.44)mug/l. Subjects in the areas with a high density of electroplating factories had significantly higher urinary Ni levels than those in the low-density areas, but both types of areas had obviously higher urinary Ni levels when compared to the non-occupationally exposed population from western countries. The health significance of elevated urinary Ni and its causative factors remain to be determined.

Trophic transfer of paralytic shellfish toxins from clams (Ruditapes philippinarum) to gastropods (Nassarius festivus).

A local strain of the dinoflagellate Alexandrium tamarense (ATCI01), which predominantly produces C2 toxin, was fed to the clams (Ruditapes philippinarum) under laboratory conditions. Concentrations of paralytic shellfish toxins (PSTs) in the dosed clams were determined by High Performance Liquid Chromatographic (HPLC) analyses, and the clams were homogenized and then fed to the gastropods (Nassarius festivus). In the toxin accumulation phase, which lasted for 42 days, concentrations of PSTs increased in the snails gradually, reaching a maximum of 1.10 nmole g(-1) at the end of the exposure period. The toxin content of the homogenized clams (food) was 13.18 nmole g(-1), which was about 12-fold higher than the PST content in the snails. Between day 43 and day 82, the snails were fed with non-toxic clams, and this period represented the depuration phase. Accumulation and depuration rates of PSTs in the snails, N. festivus, were determined by fitting the experimental data to user-defined parameters program using a one-compartment model. Two different modeling approaches were used to derive the accumulation and depuration rates. The first approach is to derive both values from the data for the toxin uptake. The second approach is to derive depuration rate from the depuration data and then to derive uptake rate, allowing for toxin depuration, from the data for toxin uptake. The first approach yielded more consistent results for the toxin concentration at the end of the uptake period, when compared with the experimental data. The toxin uptake and depuration rates were 1.64 (pmole of toxin into snail per day) per (nmole g(-1) of toxin in food) and 0.06+/-0.02 day(-1) (mean+/-SE), respectively. The toxin profiles of snails were similar to the clams, but different from the algae. Besides C toxins (C1 and C2), dcGTX2 and dcGTX3 were also detected in both clams and snails. The beta:alpha epimer ratio gradually decreased during trophic transfer and approached a ratio of 1:3 (26.4 mol%:73.6 mol% at day 42) in the snails, near the end of the accumulation period.

Interactions of paralytic shellfish toxins with xenobiotic-metabolizing and antioxidant enzymes in rodents.

Paralytic shellfish toxins (PSTs) are neurotoxins known to block voltage-gated sodium channels in intoxicated animals and humans. Their metabolism in mammalian systems and their effects on other receptors are not as well understood. In this study, we investigated the in vitro metabolism of two classes of PSTs, gonyautoxin 2/3 (GTX2/3) and C1/2 toxins (C1/2), using rat and mouse liver enzyme preparations. We also analyzed the effects of these toxins on several antioxidant and xenobiotic-metabolizing enzymes in mice. These toxins were selected for their prevalence in the coastal waters of Southern China. When the toxins were incubated with liver preparations containing Phase I and Phase II xenobiotic metabolizing enzymes and appropriate co-factors, no transformation of the toxins was detectable. When mice were given sub-lethal doses of GTX2/3, a loss of activity was observed in hepatic ethoxyresorufin-O-deethylase, penthoxyresorufin-O-deethylase, glutathione peroxidase and superoxide dismutase, but not in glutathione S-transferase, catalase and glutathione reductase. Exposure to the same mouse units of C1/2 caused only a slight reduction in the activity of penthoxyresorufin-O-deethylase and glutathione peroxidase. Our results indicated that these toxins may not be metabolized readily in mammals and that they may cause adverse effects other than sodium channel blocking.

Effects of toxic dinoflagellate Alexandrium tamarense on the energy budgets and growth of two marine bivalves.

Harmful algal blooms (HAB) may impose a serious threat to aquatic lives and human health. We determined the effects of a toxic dinoflagellate Alexandrium tamarense (clone ATCIO1, isolated from Hong Kong coastal waters) on the energy budget, quantified as scope for growth (SFG), and the growth rate of the manila clam Ruditapes philippinarum and the green-lipped mussel Perna viridis. To quantify the SFG, clams and mussels were dosed with different amounts of toxic A. tamarense for 6 days, resulting in different toxin burdens in the tissues. Clearance rate, absorption efficiency, and respiration rate were subsequently measured in these toxin containing bivalves. Clearance rate significantly declined at the highest toxin burden in the clams only, while there was no significant difference in the clearance rate among different treatments for the mussels. The respiration rate of either bivalve was not significantly affected by toxin accumulation in the tissues. In contrast, the absorption efficiency of both clams and mussels decreased, in a concentration-dependent manner for mussels but not for clams, when the tissue accumulated the toxins. With an increase in paralytic shellfish poisoning (PSP) toxin burden, SFG in both clams and mussels was significantly reduced, primarily because of the decrease of absorption efficiency. The growth rate of juvenile clam R. philippinarum, measured as an increment in tissue dry weight over a 15 d exposure period, was significantly lower during their feeding on toxic dinoflagellate than the growth rate of clams feeding on the diatom Thalassiosira pseudonana. The juvenile mussel P. viridis, however, exhibited similar growth rates after feeding on the toxic dinoflagellates and the nontoxic diatom. This study showed that SFG can provide a sensitive and integrated measure of the effect of HAB on the physiology of bivalves. Clam R. philippinarum may be more sensitive, in terms of their energy budget, to PSP toxin accumulation than the mussel P. viridis.