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Background: Childhood asthma is a common disease whose prevalence is changing. Shift in environmental exposure was one of the plausible explanations. This study investigated changes in the association between childhood asthma and ambient air pollution occurring over time. Method: A nationwide questionnaire survey concerning respiratory illness and symptoms was administered to Taiwanese elementary and middle school students in 2011 and repeatedly in 2016‐2017. During the study period, the concentrations of ambient air pollutants were obtained from the Environmental Protection Administration (EPA) monitoring stations. Generalized estimating equation models were applied to examine the association between air pollution in the past year and the risk of current asthma. Results: A total of 6346 children from the 2011 survey and 11 585 children from the 2016‐2017 survey attended schools located within a 1‐km radius of Taiwan EPA monitoring stations. The prevalence of childhood current asthma (children with physician‐diagnosed asthma and persistent asthma symptoms in the past year) increased from 7.5% to 9.6% during this period. The level of exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) in the past year was found to be associated with current asthma both in the 2011 survey (odds ratio (OR): 1.90, 95% confidence interval (CI): 1.41‐2.57) and in the 2016‐2017 survey (OR: 1.24, 95% CI: 1.04‐1.48). Conclusion: Improved air quality has reduced the effect of PM2.5 on childhood asthma, but air quality remains a health concern in Taiwan. [ABSTRACT FROM AUTHOR]

The neurotoxic effects of certain heavy metals are well established, but only a few studies have investigated the joint effect of concurrent exposure to multiple ones. The study aims to evaluate the association between mixed exposure to neurotoxic metals and the psychosocial behavior of preschool children. Using a stratified sampling strategy, we recruited participants from 105 kindergartens in 41 townships of Taiwan and excluded those with blood lead levels ≥ 3.5 µg/L. The first-morning void urines were collected and analyzed for cadmium, manganese, arsenic, chromium, lead, and nickel concentrations using inductively coupled plasma mass spectrometry. We applied the parentally reported Strengths and Difficulties Questionnaire (SDQ) and Swanson, Nolan, and Pelham IV (SNAP-IV) scales to evaluate the psychosocial behaviors. Multiple linear regressions were utilized to evaluate the associations between each heavy metal and the outcomes, while the mixed effect of concurrent exposure was estimated by using a Quantile g-computation approach. A total of 977 preschool children were included in the study, and the mean (SD) age was 5.7 (0.7) years old. In single pollutant models, we observed adverse effects of urinary manganese, nickel, arsenic, and lead on the specific subsets of SDQ. Furthermore, the combined effect of six heavy metals significantly affected the hyperactivity/inattention symptoms (beta = 0.46, 95% CI: 0.13–0.78, with all metals increased by one quartile), and chromium and lead were the two major contributors. Similar detrimental effects of urinary cadmium and lead were also observed in the SNAP-IV subsets, although the joint effect analysis was not significant. The study provided evidence that concurrent exposure to multiple heavy metals may exert increased risks of hyperactivity/inattention in children compared to single pollutant exposure. Further studies are needed to verify our findings regarding mixed exposure to multiple neurotoxic metals. [Display omitted] • We recruited 977 participants aged 5–6 years from a population-based cohort. • To assess mixed exposure to Cd, Mn, As, Cr, Pb, and Ni on psychosocial behaviors. • Mixed metal exposure increased the risk of inattention/hyperactivity symptoms. • Cr and Pb contributed to two-thirds of the adverse effects. • Low-level Pb exposure might still increase the risk of ADHD symptoms. [ABSTRACT FROM AUTHOR]

Background: Perfluoroalkyl substance (PFAS) exposure was found associated with atopic diseases. Atopic dermatitis (AD) is a childhood skin disorder. However, the effect of interaction between PFASs and glutathione S-transferase (GST) T1/M1 genotype on AD remains unclear. Objective: To investigate the association between gene-environmental interaction and childhood AD using a birth cohort study. Methods: From 2001 to 2005, 1,264 mother–newborn pairs were recruited from eight Taiwanese maternity hospitals. PFAS levels and Genotypes were analysed from cord blood. Information on children’s health status including AD occurrence was obtained via phone interviews at 6 months and 2 years. Cord plasma concentrations of nine PFASs were measured via ultra-high performance liquid chromatography/tandem mass spectrometry. GSTT1/M1 was genotyped (null/present) via polymerase chain reaction. Environment-gene interaction effects on AD were assessed using multiple logistic regression analysis. Results: Overall, 839 mother–newborn pairs completed all measurements. The prevalence of ever having physician-diagnosed AD by 2 years of age was 5.4%. Among PFASs, perfluorooctanoic acid (PFOA) was positively associated with AD adjusted for potential confounders. After grouping PFOA levels into three groups: undetected, below and above the median in those with detected, children in above the median group who had the GSTT1-null, or GSTM1-null genotype exhibited a higher odds ratio for AD (OR [95%CI] = 3.45 [1.26–9.99] and 2.92 [1.12–7.91], respectively) as compared to the undetected group. Conclusions: Our data demonstrated that in-utero PFOA exposure with GSTT1/M1 null genotype were associated with AD. Minimizing early-life PFAS exposure may help against AD development, especially in genetically susceptible individuals. [ABSTRACT FROM AUTHOR]

Phthalates have become important environmental pollutants due to their high exposure frequency in daily life; thus, phthalates are prevalent in humans. Although several epidemiologic surveys have linked phthalates with several adverse health effects in humans, the molecular events underlying phthalate exposure have not been fully elucidated. The purpose of this study was to reveal associations between phthalate exposure and the serum metabolome in Taiwanese children using a metabolomic approach. A total of 256 Taiwanese children (8–10 years old) from two cohorts were enrolled in this study. Twelve urinary phthalate metabolites were analyzed by high-performance liquid chromatography/tandem mass spectrometry, while a nuclear magnetic resonance-based metabolomic approach was used to record serum metabolic profiles. The associations between metabolic profiles and phthalate levels were assessed by partial least squares analysis coupled with multiple linear regression analysis. Our results revealed that unique phthalate exposures, such as mono-isobutyl phthalate, mono-n-butyl phthalate, and mono (2-ethyl-5-oxohexyl) phthalate, were associated with distinct serum metabolite profiles. These phthalate-mediated metabolite changes may be associated with perturbed energy mechanisms, increased oxidative stress, and lipid metabolism. In conclusion, this study suggests that metabolomics is a valid approach to examine the effects of environmental-level phthalate on the serum metabolome. This study also highlighted potentially important phthalates and their possible effects on children. [Display omitted] • Serum metabolic perturbation was associated with urinary phthalate levels in children. • Levels of MEOHP, MnBP, and MiBP were critical to metabolic changes in child serum. • The perturbed metabolites may be involved in energy metabolism, oxidative stress, and lipid metabolism. • The metabolomic approach is a powerful tool for studying the health impacts of chemicals at an environmental level. [ABSTRACT FROM AUTHOR]

Although recent epidemiologic studies have focused on some of the health effects of perfluoroalkyl substance (PFASs) exposure in humans, the associations between PFASs exposure and the lipidome in children are still unclear. The purpose of this study was to assess lipid changes in children to understand possible molecular events of environmental PFASs exposure and suggest potential health effects. A total of 290 Taiwanese children (8–10 years old) were included in this study. Thirteen PFASs were analyzed in their serum by high-performance liquid chromatography-tandem mass spectrometry (LC-MS). MS-based lipidomic approaches were applied to examine lipid patterns in the serum of children exposed to different levels of PFASs. LC coupling with triple quadrupole MS technology was conducted to analyze phosphorylcholine-containing lipids. Multivariate analyses, such as partial least squares analysis along with univariate analyses, including multiple linear regression, were used to analyze associations between s exposure and unique lipid patterns. Our results showed that different lipid patterns were discovered in children exposed to different levels of specific PFASs, such as PFTrDA, PFOS, and PFDA. These changes in lipid levels may be involved in hepatic lipid metabolism, metabolic disorders, and PFASs-membrane interactions. This study showed that lipidomics is a powerful approach to identify critical PFASs that cause metabolite perturbation in the serum of children and suggest possible adverse health effects of these chemicals in children. [Display omitted] • Levels of PFOS, PFTrDA, and PFDA were associated with lipid perturbations in child serum. • Lipid changes may be involved in metabolic disorder and membrane dysfunction. • Lipidomics is a powerful tool to identify critical contaminants at environmental levels. Lipidomic approaches in environmental studies are useful to identify critical perfluoroalkyl substances and suggest their potential health effects on children. [ABSTRACT FROM AUTHOR]

• We assessed the association of phthalate exposure and antibody concentrations in children. • Certain phthalates exposures were associated with decreased antibody concentrations. • Phthalate exposure is suggested for considerations in re-booster vaccines for teenagers. Phthalic acid esters (PAE) are widely used during chemical synthesis and do not form covalent linkages with products. It has been reported that exposure to PAE affects the immune response. However, their effect on antibody concentrations in children is still under investigation. We aimed to examine the association between early-life phthalate exposure and antibody concentrations in children in a longitudinal birth cohort established in 2000–2001. We recruited 398 neonates in central Taiwan and followed them up every 2–3 years, with various antibody-related studies at 11- and 14-year follow-ups. Seven urinary phthalate metabolites were quantified in mothers during pregnancy and children aged 11 years. Four antibody concentrations were analyzed in children aged 11 and 14 years. The percent change in antibody concentrations from ages 11 to 14 years was calculated and its association with phthalate exposure was evaluated via multivariate regression analysis. Eighty-one followed-up children were with sufficient data. After adjusting for prenatal exposure and other confounders, double concentrations of the urinary sum of di-2-ethylhexyl phthalate (ΣDEHPm) and mono-n-butyl phthalate (MnBP) were associated with a 18.06% (95% CI = 3.34%, 32.78%) and 22.53% decrease (95% CI = 3.39%, 41.66%) in antibody concentration against hepatitis B, respectively. Phthalate exposure was found to be related to decreased antibody concentrations against hepatitis B (DEHP, DBnP) in the early teens. This exposure is suggested to be considered for clinical re-booster vaccines among junior high school students. Further verification with additional cohorts and studies on the underlying mechanisms of phthalate exposure are warranted. [ABSTRACT FROM AUTHOR]

Background We recently reported the relationship between exposure to ambient air pollutants and changes in lung function and nasal inflammation among schoolchildren. A study was conducted to investigate whether antioxidation genotypes influence these associations. Methods A follow-up study of 97 schoolchildren was conducted in New Taipei City, Taiwan. A structured respiratory health questionnaire was administered in September 2007, followed by monthly spirometry and measurement of nasal inflammation from October 2007 to November 2009. During the study period, complete daily monitoring data for air pollutants were obtained from the Environmental Protection Administration monitoring station and Aerosol Supersite. The genotypes of glutathione S-transferase (GST) subunits M1, T1, P1 and superoxide dismutases subunit 2 (SOD2) were characterized. Mixed-effects models were used, adjusting for known confounders. Result GSTM1 null children had significant PM 2.5 -related increment in leukocyte (8.52%; 95% confidence interval (CI): 3.13–13.92%) and neutrophil (9.68%; 95% CI: 4.51–14.85%) in nasal lavage. Ozone levels were significantly and inversely associated with forced expiratory flow at 25% of forced vital capacity (FEF 25% ) (−0.43 L/s; 95% CI: −0.58,−0.28 L/s) in SOD2 Ala16 variant children. Conclusion In this longitudinal study of schoolchildren. Our data provide evidence that antioxidation genotype modifies the airway inflammation caused by PM 2.5 . Antioxidation genotype also acts as an effect modifier, but not strong, in ozone-related small airway function response. [ABSTRACT FROM AUTHOR]

Previous studies have reported sources of particle number pollution in urban air, but have not evaluated relationships between respiratory health and these sources. We compared, among children with asthma or allergies, the associations of spirometric lung functions with increased exposure to source-specific versus size-segregated particle number concentrations (PNC). Hourly measurements of PNC were acquired from the aerosol Supersite in New Taipei, Taiwan. Spirometry (FVC, FEV 1 , and FEF) was recorded monthly for 59 children with asthma or allergies at five schools during 2007–2008. After co-pollutant adjustment for ozone, we found a 0.21 and 0.17 L decrease in FVC [95% confidence interval (CI): − 0.35, − 0.06 L] and FEV 1 (95% CI: − 0.32, − 0.03 L), respectively, with an interquartile range increase (1879.7 #/cm 3 ) in secondary aerosol contribution observed on the previous day. In addition, we found no significant associations of FVC with accumulation mode (0.1 μm < aerodynamic diameter < 2.5 μm) PNC. Our findings suggest that PNC of secondary origin is most responsible for pollution-related respiratory effects among children living in urban Taipei. Studies that rely on exposure to size-segregated PNC may underestimate PM health impacts. [ABSTRACT FROM AUTHOR]

Abstract: Background: In our previous longitudinal study, we found that exposure to current levels of ambient total fungal spores was related to a reduction of childhood lung function. However, the biological properties of various taxa of fungal spores varied greatly, as well as their health effects. In this study, we aimed to determine whether any specific fungal spores were responsible for observed changes in lung function. Methods: Measurement of lung function was conducted for 100 elementary and middle-school students on 5–10 occasions from October 2007 to November 2009 in New Taipei City, Taiwan. During the week of each lung function measurement, continuous daily concentrations of fungal spores were measured from Sunday to Saturday. The counts of fungal spores belonging to specific taxa were identified. A mixed-effect model with repeated measurements was used to analyze the association of lung function and exposure to each specific taxon of fungal spores. Forward stepwise regression was applied to determine which specific fungal spores were the most closely related to lung function changes. The non-linear relationship was examined using a generalized additive model. The piecewise linear regression was then applied to determine the threshold value. Results: A total of 824 measurements were obtained from 100 participants. Among all the species of fungal spores, only Cladosporium spores were found to be negatively associated with forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) one day later. This association was stronger than the one between the total spore counts and lung function. The threshold of exposure where lung function effect became observable was approximately 1500spores/m3. Conclusion: This study showed that ambient Cladosporium was most strongly associated with the observed lung function changes among schoolchildren. Replication of these preliminary findings in other geographic areas with different populations would be warranted. [Copyright &y& Elsevier]

Exposure to ambient fine particles, particulate matter with an aerodynamic diameter of ≤2.5 μm (PM 2.5), is a public health concern. Concentrations of ambient PM 2.5 have changed temporally in the past 10 years after a series of action policies for improving air quality were implemented in Taiwan. In this study, temporal changes in the relationship between PM 2.5 and lung function among children were investigated. A nationwide respiratory health survey was conducted among Taiwanese elementary and middle school students in 2011 and again in 2016–2017. A questionnaire was administered to students, for whom forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1) were measured using spirometry. During the study period, monthly concentrations of ambient PM 2.5 were obtained from the monitoring stations of the Environmental Protection Administration. Lung function measurements were compared with ambient PM 2.5 exposure using mixed-effects models. In the 2011 survey (mean PM 2.5 : 40.6 μg/m3), exposure to PM 2.5 in the preceding 1–2 months was associated with a 2.2% decrease (95% confidence interval [CI]: −4.1%, −0.3%) in FVC and a 2.3% decrease (95% CI: −4.0%, −0.5%) in FEV 1. By contrast, a significant relationship between PM 2.5 concentrations and lung function was not observed in the 2016–2017 survey (mean PM 2.5 : 30.0 μg/m3). As improvement in air quality over time, the negative relationship between PM 2.5 and childhood lung function tend to be not significant. • Repeated surveys among similar populations provided valid temporal comparisons of exposure and health. • The decreases in PM 2.5 level over time were observed in each district of Taiwan. • The PM 2.5 -childhood lung function relationship tended to be not significant over time. [ABSTRACT FROM AUTHOR]