Cigarette smoke-induced dysbiosis: comparative analysis of lung and intestinal microbiomes in COPD mice and patients.

BACKGROUND: The impact of cigarette smoke (CS) on lung diseases and the role of microbiome dysbiosis in chronic obstructive pulmonary disease (COPD) have been previously reported; however, the relationships remain unclear. METHODS: Our research examined the effects of 20-week cigarette smoke (CS) exposure on the lung and intestinal microbiomes in C57BL/6JNarl mice, alongside a comparison with COPD patients' intestinal microbiome data from a public dataset. RESULTS: The study found that CS exposure significantly decreased forced vital capacity (FVC), thickened airway walls, and induced emphysema. Increased lung damage was observed along with higher lung keratinocyte chemoattractant (KC) levels by CS exposure. Lung microbiome analysis revealed a rise in Actinobacteriota, while intestinal microbiome showed significant diversity changes, indicating dysbiosis. Principal coordinate analysis highlighted distinct intestinal microbiome compositions between control and CS-exposed groups. In the intestinal microbiome, notable decreases in Patescibacteria, Campilobacterota, Defferibacterota, Actinobacteriota, and Desulfobacterota were observed. We also identified correlations between lung function and dysbiosis in both lung and intestinal microbiomes. Lung interleukins, interferon-É£, KC, and 8-isoprostane levels were linked to lung microbiome dysbiosis. Notably, dysbiosis patterns in CS-exposed mice were similar to those in COPD patients, particularly of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 patients. This suggests a systemic impact of CS exposure. CONCLUSION: In summary, CS exposure induces significant dysbiosis in lung and intestinal microbiomes, correlating with lung function decline and injury. These results align with changes in COPD patients, underscoring the important role of microbiome in smoke-related lung diseases.

A nationwide case-referent study on elevated risks of adenocarcinoma lung cancer by long-term PM2.5 exposure in Taiwan since 1997.

BACKGROUND: The effects of long-term PM2.5 exposures since 1968 on adenocarcinoma lung cancer (AdLC) were not studied before. METHODS: This case-referent study used nationwide cancer registry data since 1997 and air pollution data since 1968 in Taiwan to estimate risks of 30-year PM2.5 exposures on AdLC. Cases were all AdLC, while references were all non-AdLC. Individuals' 30-year PM2.5 exposures were estimated by PM2.5 levels at their residence for 30 years prior their diagnosis dates. We applied multiple logistic regression analyses to estimate PM2.5 exposures on incidence rate ratios (IRRs) between cases and references, adjusting for sex, age, smoking, cancer stage, and EGFR mutation. RESULTS: Elevation in annual ambient PM2.5 concentrations since 1968 were associated with increase in annual age-adjusted AdLC incidence since 1997. AdLC incidences were higher among females, nonsmokers, the elderly aged above 65, cases of stages IIIB to IV, and EGFR mutation. Study subjects' PM2.5 exposures averaged at 33.7 ± 7.4 µg/m3 with 162 ± 130 high PM2.5 pollution days over 30 years. Multiple logistic models showed an increase in 10 µg/m3 of PM2.5 exposures were significantly associated with 1.044 of IRR between all AdLC and all non-AdLC cases during 2011-2020. Our models also showed that females and nonsmokers and adults less than 65 years had higher IRRs than their respective counterparts. Restricted analyses showed similar effects of PM2.5 exposures on IRRs between stage 0-IIIA and IIIB-IV cases and between EGFR+ and EGFR- cases. CONCLUSIONS: Long-term exposures to PM2.5 over 30 years were associated with elevated risks of AdLC against non-AdLC, regardless of gender, age, smoking status, cancer stage, or EGFR mutation.

Data on lung and intestinal microbiome after air pollution exposure in ageing rats.

Air pollution has been linked to respiratory diseases, and urban air pollution can be attributed to a number of emission sources. The emitted particles and gases are the primary components of air pollution that enter the lungs during respiration. Particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) can deposit deep into the respiratory tract via inhalation and has been proposed as a causative agent for adverse respiratory health. In addition, the lung contains a diverse microbial community (microbiome) that maintains normal homeostasis and is significantly altered in a variety of pulmonary disorders. Air pollution, specifically PM2.5, has previously been shown to significantly alter the composition of the lower airway microbiome, which has been linked to decreased lung function in chronic obstructive pulmonary disease (COPD) patients. Surprisingly, the intestinal microbiome has also been implicated in the modulation of pulmonary inflammatory diseases. Therefore, dysbiosis of the lung and intestinal microbiomes pose significant negative effects on human health. This dataset describes the microbial community profiles of the lungs and intestines of ageing rats exposed to ambient unconcentrated traffic-related air pollution for three months. The whole-body exposure system was equipped with and without high efficiency particulate air (HEPA) filtration (gaseous vs. PM2.5 pollution). The data can provide valuable information on lung and intestinal microbiome changes, including that which was only found after traffic-related air pollution exposure.

Association between ambient air pollution exposure and insomnia among adults in Taipei City.

Ambient air pollution was known to cause central nervous system diseases and depressive symptoms. In this study, we examined the associations between air pollution exposure and the prevalence of insomnia in Taipei City of Taiwan. We applied the health information system of electrical medical records of Taipei City Hospital to collect a total of 5108 study subjects (insomniacs N = 912 and non-insomniacs N = 4196) over 18 years old from the family medicine and internal medicine outpatients of six branches of Taipei City Hospital. These patients were grouped into insomniacs and non-insomniacs following the primary insomnia diagnosis (ICD9:780.52, 780.54, 307.41, 307.42, ICD10: G47.00, G47.01, G47.09, F51.01, F51.09) and the prescription times of anxiolytics and hypnotics. We estimated one-year average concentrations of PM2.5, ozone, and NOx before the first date of insomnia diagnosis and the last date of outpatient visit for insomniacs and non-insomniacs, respectively, by using the data of nearest air quality monitoring stations relative to study subjects' residential addresses. Logistic regression analysis was employed to examine the independent effects of air pollution concentrations on the risk of insomnia. One-year average PM2.5, ozone, and NOx levels for insomniacs was significantly higher than those of non-insomniacs. After adjusting for confounding factors, increase each 1(µg/m3) in one-year average PM2.5 showed a statistically significant association with insomnia (the odds ratio 1.610, 95% CI [1.562,1.660]). As to multi pollutants, one-year average PM2.5 (1.624, [1.570, 1.681] and ozone (1.198, [1.094, 1.311]) exposure showed a significant association with insomnia. Subgroup analysis revealed that the influence of PM2.5 and ozone on insomnia have significant risks in people with major chronic disease. This study demonstrated a positive association between PM2.5 and ozone exposure and the prevalence of hypnotic-treated insomnia. Especially, the people with major chronic diseases were with obvious effect of PM2.5 and ozone on risk of insomnia.

Effects of antibiotics and metals on lung and intestinal microbiome dysbiosis after sub-chronic lower-level exposure of air pollution in ageing rats.

We investigated the effects of antibiotics, drugs, and metals on lung and intestinal microbiomes after sub-chronic exposure of low-level air pollution in ageing rats. Male 1.5-year-old Fischer 344 ageing rats were exposed to low-level traffic-related air pollution via whole-body exposure system for 3 months with/without high-efficiency particulate air (HEPA) filtration (gaseous vs. particulate matter with aerodynamic diameter of ≤2.5 µm (PM2.5) pollution). Lung functions, antibiotics, drugs, and metals in lungs were examined and linked to lung and fecal microbiome analyses by high-throughput sequencing analysis of 16 s ribosomal (r)DNA. Rats were exposed to 8.7 µg/m3 PM2.5, 10.1 ppb NO2, 1.6 ppb SO2, and 23.9 ppb O3 in average during the study period. Air pollution exposure decreased forced vital capacity (FVC), peak expiratory flow (PEF), forced expiratory volume in 20 ms (FEV20), and FEF at 25∼75% of FVC (FEF25-75). Air pollution exposure increased antibiotics and drugs (benzotriazole, methamphetamine, methyl-1 H-benzotriazole, ketamine, ampicillin, ciprofloxacin, pentoxifylline, erythromycin, clarithromycin, ceftriaxone, penicillin G, and penicillin V) and altered metals (V, Cr, Cu, Zn, and Ba) levels in lungs. Fusobacteria and Verrucomicrobia at phylum level were increased in lung microbiome by air pollution, whereas increased alpha diversity, Bacteroidetes and Proteobacteria and decreased Firmicutes at phylum level were occurred in intestinal microbiome. Lung function decline was correlated with increasing antibiotics, drugs, and metals in lungs as well as lung and intestinal microbiome dysbiosis. The antibiotics, drugs, and Cr, Co, Ca, and Cu levels in lung were correlated with lung and intestinal microbiome dysbiosis. The lung microbiome was correlated with intestinal microbiome at several phylum and family levels after air pollution exposure. Our results revealed that antibiotics, drugs, and metals in the lung caused lung and intestinal microbiome dysbiosis in ageing rats exposed to air pollution, which may lead to lung function decline.

Comparison of the PCB serum levels among mother-child pairs in areas of Eastern Japan and Central Taiwan.

Polychlorinated biphenyls (PCBs) have been prohibited for two decades in Japan and Taiwan. The aim of this study was to compare the PCB congeners in maternal and cord serum between two countries. Our study subjects were 248 and 100 mother-child pairs in Japan and Taiwan. The measured levels of 23 serum PCB congeners between two countries were analyzed using gas chromatography-electron capture negative ionization quadrupole mass spectrometry (GC-NICI-qMS). The statistical comparisons were conducted by Student's t-test and principal component analysis with further stratification by maternal age and parity. The maternal total PCBs levels in Japan (426 ± 244 pg/g wet wt) were significantly higher than those in Taiwan (254 ± 155 pg/g wet wt), and the similar results were found in cord total PCBs levels (97 ± 76 and 58 ± 87 pg/g wet wt). It showed different distributions of PCB congeners between two countries. Whether in maternal or cord serum, the CB138, CB153 and CB180 were the highest detectable congeners whether in Japan or Taiwan. And, the CB66, CB99, CB206 and CB209 were only detected in maternal serum of Taiwan. The women of advanced maternal age had higher levels of PCB congeners, especially in Taiwan, and the primiparous women had higher levels of PCB congeners in two countries. In summary, the PCB congeners in Japan's mother-child pairs were with higher levels and different distributions when compared to those in Taiwan, and the maternal age and parity were important factors associated with the PCB levels.

Characteristics of neonicotinoid and metabolite residues in Taiwanese tea leaves.

BACKGROUND: Neonicotinoids are widely used insecticides, and tea is a popular non-alcoholic beverage in Taiwan. However, the levels of neonicotinoids in Taiwanese tea leaves remain unclear. Therefore, this study aims to understand the characteristics of neonicotinoid and metabolite residues in Taiwanese tea leaves. METHODS: In this study, 12 tea leaf samples were collected in Taiwan and extracted by solid-phase extraction before analysis by liquid chromatography-tandem mass spectrometry. In addition, the levels of neonicotinoids were compared with the maximum residue level standards from other countries. RESULTS: In Taiwanese tea leaves, five neonicotinoids and seven metabolites were detected. Different tea species influenced the levels of neonicotinoids and their metabolites in the present study. Moreover, the levels of neonicotinoids and their metabolites in partially fermented leaves were higher than in completely fermented leaves. In Jin-Xuan tea, the levels of neonicotinoids and their metabolites in most winter-harvested teas were lower than in summer-harvested teas. CONCLUSION: The residue levels of neonicotinoids and their metabolites were detectable in Taiwanese tea leaves. Moreover, different tea species, manufacturing processes, and harvest seasons might influence the levels of these pesticides. Therefore, the government should monitor the use of neonicotinoids. © 2021 Society of Chemical Industry.

Air-polluted environmental heavy metal exposure increase lung cancer incidence and mortality: A population-based longitudinal cohort study.

BACKGROUND: An increased risk of lung cancer has been observed due to exposure to certain environmental heavy metals. This study elucidated the role of air-polluted heavy metals in the development of lung cancer. METHODS: A longitudinal cohort study involving the general population was conducted to compare heavy metal content among lung cancer patients. The urine concentrations of heavy metals were measured. Questionnaire surveys were designed to collect exposure-related demographic and lifestyle data of the study subjects. RESULTS: Participants residing near the petrochemical industrial area with higher air Cd concentration had relatively higher urinary concentration of Cd. After adjusting for sociodemographic and behavioral factors, tobacco smoking and air pollution remained as potential sources of Cd exposure. An increased prevalence of lung cancer was observed in the highly polluted zone. The risk of lung cancer incidence increased 1.25-fold for each 1 µg/g-creatinine increase in urine Cd level. Patients with lung cancer had significantly higher urinary Cd concentrations. Lung cancer patients with higher urinary Cd level had significantly poor survival (urine Cd level ≥ 1.58 vs <1.58 µg/g-creatinine; survival, medium, 192.0 vs 342.5 days, p < 0.001). At the longitudinal follow-up, participants with higher urinary Cd level had a higher risk of lung cancer incidence (urine Cd level ≥ 1.58 vs <1.58 µg/g-creatinine: 3.91% v.s. 0.87%, hazard ratio: 4.65, p < 0.001). CONCLUSIONS: Accumulation of Cd could be a risk of lung cancer occurrence. High exposure to Cd may result in poor prognosis in lung cancer patients.

Lipidomics of children and adolescents exposed to multiple industrial pollutants.

BACKGROUND: There are limited studies on the lipidomics of children and adolescents exposed to multiple industrial pollutants. OBJECTIVES: In this study, we aimed to investigate lipid profile perturbations in 99 children and adolescents (aged 9-15) who lived in a polluted area surrounding the largest petrochemical complex in Taiwan. Previous studies have reported increased risks of acute and chronic diseases including liver dysfunctions and chronic kidney disease (CKD) in residents living in this area. METHODS: We measured urinary concentrations of 11 metals and metalloids and polycyclic aromatic hydrocarbons (PAHs) metabolite 1-hydroxypyrene (1-OHP) as exposure biomarkers, and urinary oxidative stress biomarkers and serum acylcarnitines as early health effect biomarkers. The association between individual exposure biomarkers and early health effect biomarkers were analyzed using linear regression, while association of combined exposure biomarkers with four oxidative stress biomarkers and acylcarnitines were analyzed using weighted quantile sum (WQS) regression. Lipid profiles were analyzed using an untargeted liquid chromatography mass spectrometry-based technique. "Meet-in-the-middle" approach was applied to identify potential lipid features that linked multiple industrial pollutants exposure with early health effects. RESULTS: We identified 15 potential lipid features that linked elevated multiple industrial pollutants exposure with three increased oxidative stress biomarkers and eight deregulated serum acylcarnitines, including one lysophosphatidylcholines (LPCs), four phosphatidylcholines (PCs), and two sphingomyelins (SMs) that were up-regulated in high exposure group compared to low exposure group, and two LPCs, four PCs, and two phosphatidylinositols (PIs) down-regulated in high exposure group compared to low exposure group. CONCLUSION: Our findings could provide information for understanding the health effects, including early indicators and biological mechanism identification, of children and adolescents exposed to multiple industrial pollutants during critical stages of development.

Relationship between renal function and metal exposure of residents living near the No. 6 Naphtha Cracking Complex: A cross-sectional study.

BACKGROUND/PURPOSE: Heavy metals impair renal function, causing chronic kidney disease (CKD), and the petrochemical industry is one of the major environmental metal emission sources. This study aimed to investigate the relationship between renal function and metal exposure among the Taiwanese residents living near a petrochemical industry site. METHODS: We recruited residents near the No. 6 Naphtha Cracking Complex, and they were categorized into a high-exposure (HE) group (N = 190) in Taisi Village and a low-exposure (LE) group (N = 1184) in other villages of Dacheng Township in Changhua County of Taiwan. The urinary nickel, chromium, and vanadium levels of the study subjects were measured and the levels were standardized by urine creatinine, and the estimated glomerular filtration rates (eGFRs) were calculated to estimate renal function by one-time health data. Linear regression models were applied to illustrate the correlations between the distance to the complex and urinary metal levels and renal function; linear and logistic regression models were applied to evaluate the associations between urinary metal levels and renal function indicators. RESULTS: The study subjects living closer to the petrochemical complex had significantly higher urinary nickel, chromium, and vanadium levels and worse renal function than study subjects living farther away. The urinary nickel and chromium levels of the study subjects were associated with their renal function indicators. When the subject's urinary nickel level increased 1-fold, the eGFR level significantly decreased by 0.820 ml/min/1.73 m2. CONCLUSION: Residents living closer to the petrochemical industry were exposed to higher metal levels and had worse renal function, and the nickel exposure of residents was potentially related to their decline in renal function.

Assessment of the hyperlipidemia risk for residents exposed to potential emitted metals in the vicinity of a petrochemical complex.

Hyperlipidemia, which is associated with certain environmental factors, is a risk factor for cardiovascular disease. Heavy metals are important pollutants from industrial emissions. However, the relationship between the exposure to heavy metals and the occurrence of hyperlipidemia is limited. This study aimed to investigate the association between serum metal levels and the risk of hyperlipidemia in adults living near a petrochemical complex. Our study subjects were 959 residents aged above 35 years in 11 townships near the largest petrochemical complex in central Taiwan. The serum levels of chromium, arsenic, and mercury in the study subjects were measured. The basic characteristics of the study subjects were collected via a questionnaire survey, and the levels of blood lipid biomarkers were analyzed by health examination. The definition of hyperlipidemia was defined in the provided guidelines. Adjusted generalized linear and logistic regression models were applied to evaluate the associations between petrochemical-related metal exposure and hyperlipidemia. The study subjects had chromium, arsenic, and mercury serum levels of 3.24±3.45, 3.45±4.66, and 1.24±1.08 (µg/L), respectively, and close proximity of the study subjects to the petrochemical complex was significantly associated with increased serum metal levels. The results showed that the total cholesterol levels were significantly associated with the increased serum chromium, arsenic, and mercury levels. And, the LDL-C levels were significantly associated with the increased serum mercury levels. In addition, the increased serum arsenic and mercury levels of the study subjects were significantly associated with higher odds ratios for abnormal total cholesterol levels and the risk of hyperlipidemia. Residing in close proximity to a petrochemical complex and high arsenic and mercury exposure were associated with elevated blood lipid levels and an increased risk of hyperlipidemia among the residential population in the vicinity of the petrochemical industry.

Emission-related Heavy Metal Associated with Oxidative Stress in Children: Effect of Antioxidant Intake.

Heavy metals, the common pollutants emitted from industrial activities, are believed to cause harmful effects, partially through the mechanism of elevated oxidative stress, and antioxidant intake has been hypothesized to provide a potential protective effect against oxidative stress. This study aims to investigate the heavy metal exposure and the associated oxidative damage of young children living near a petrochemical complex and to assess the protective effect of antioxidant intake. There were 168 children recruited from the kindergartens near a huge petrochemical complex, with 87 as the high exposure group and 81 as the low exposure group. Urinary concentrations of eleven metals were detected by inductively coupled plasma mass spectrometry, and four biomarkers of oxidative stress were measured in urine by liquid chromatography-tandem mass spectrometry. The food frequency questionnaire was collected to assess participants' intake of antioxidants. Multiple linear regression was performed to determine the predictors of metals for oxidative stress and to measure the beneficial effect of antioxidants. Weighted quantile sum regression was performed to determine the contributors among metals to the oxidative stress. Results showed that high exposure group had significantly higher concentrations of chromium, manganese, nickel, arsenic, strontium, cadmium, and lead when compared to those in low exposure group. There was no obviously difference on the total antioxidant intake and dietary profile between two groups. The elevated levels of two oxidative stress markers were significantly associated with most of the urinary metal concentrations in all study subjects after adjusting confounders, while no significant association was found between oxidative stress and antioxidant intake. Among the metals, mercury and strontium showed the dominated contributions for elevated levels of oxidative stress. It concluded that higher metal exposure was associated with elevated oxidative stress but with no protective effect by antioxidant intake among the young children residents near a petrochemical industry.

Liver fibrosis associated with potential vinyl chloride and ethylene dichloride exposure from the petrochemical industry.

BACKGROUND: The understanding of the relationship between exposure to carcinogenic vinyl chloride (VCM) and ethylene dichloride (EDC) and liver fibrosis is limited. OBJECTIVE: This study aimed to investigate the associations between the urinary metabolite levels of VCM and EDC and the risk of liver fibrosis in residents living near a petrochemical complex. METHODS: Our study comprised 447 adult residents of two townships with questionnaire survey and health examination near the largest petrochemical complex in central Taiwan. The urinary levels of thiodiglycolic acid (TdGA), the metabolite of VCM and EDC, were detected in study subjects. We utilized fibrosis-4 (FIB-4) as the noninvasive liver fibrosis index. Adjusted linear model was applied to evaluate the associations between the distance from the complex and the urinary TdGA levels. Adjusted logistic regression model was applied to evaluate the associations between the urinary TdGA levels and the risk of liver fibrosis. RESULTS: The study subjects living in the closer township had significant higher urinary TdGA levels than those living in the more distant township (269.6 ± 200.7 vs. 199.2 ± 164.7 µg/g creatinine) (p < 0.001). It showed that urinary TdGA levels were decreased 0.53-fold when the distances from the complex were increased 1-fold after adjusting for confounding factors. It demonstrated that the study subjects with the highest TdGA levels (>343.3 µg/g creatinine) had a higher risk of FIB-4>1.29 (OR = 2.09; 95% CI: 1.17, 3.78), and those with higher TdGA levels (232.7 to 343.3 µg/g creatinine) had a marginally higher risk of FIB-4>1.29 (OR = 1.65; 95% CI: 0.94, 2.90). CONCLUSION: The residents living closer to the VCM/PVC plant in the petrochemical complex had higher urinary TdGA levels, which were associated with an increased risk of fibrosis. This confirmed that the EDC and VCM potentially emitted from the petrochemical industry may have an impact on the liver health of nearby residents.

Associations of soluble metals and lung and liver toxicity in mice induced by fine particulate matter originating from a petrochemical complex.

Adverse health effects have been observed in nearby residents due to exposure to petrochemical-derived chemicals. The objective of this study was to examine associations of soluble metals with lung and liver toxicity in fine particulate matter (PM2.5) in the vicinity of a petrochemical complex. PM2.5 was collected in the vicinity of a petrochemical complex of Mailiao Township (Yunlin County, Taiwan) to investigate lung and liver toxicity in BALB/c mice. The PM2.5 concentration was 30.2 ± 11.2 µg/m3, and the PM2.5 was clustered in major local emissions (19.1 µg/m3) and minor local emissions (14.1 µg/m3) using a k-means clustering model. The PM2.5 (50 and 150 µg/kg) and PM2.5-equivalent soluble nickel (Ni), vanadium (V), and lead (Pb) concentrations were intratracheally instilled into BALB/c mice. PM2.5 and V significantly decreased the tidal volume after exposure (p < 0.05). The peak expiratory flow (PEF) and peak inspiratory flow (PIF)/PEF ratio were significantly altered by 150 µg/kg V (p < 0.05). V and Pb significantly increased total protein and lactate dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (BALF) (p < 0.05). Interleukin (IL)-6 in BALF significantly increased after exposure to Pb (p < 0.05) accompanied by lung inflammatory infiltration. PM2.5 and Pb significantly increased levels of 8-isoprostane (p < 0.05). The level of caspase-3 activity significantly increased after exposure to Pb (p < 0.05). LDH in the liver was significantly increased by PM2.5 (p < 0.05). 8-Isoprostane in the liver was significantly increased by PM2.5 and Pb (p < 0.05). IL-6 in the liver was significantly increased by PM2.5, Ni, V, and Pb after exposure (p < 0.05), accompanied by liver inflammatory infiltration. Our results demonstrated that V in PM2.5 was associated with an increase in 8-isoprostane for all emissions and major local petrochemical emissions. In conclusion, V contributes to in vivo liver toxicity induced by PM2.5 in the vicinity of a petrochemical complex.

Associations between renal functions and exposure of arsenic and polycyclic aromatic hydrocarbon in adults living near a petrochemical complex.

BACKGROUND: The understanding for the impact of petrochemical pollutants exposure on renal functions is limited. OBJECTIVES: Our study examined the associations between renal functions and pollutants exposure in adult residents living in the vicinity of a petrochemical industry. METHODS: We recruited 2069 adult residents near a big petrochemical complex in Taiwan in 2009-2012, and they were categorized into high exposure (HE) and low exposure (LE) groups based on their address to source by 10 km radius. Study subjects were measured the urinary levels of arsenic, cadmium, mercury, thallium, and 1-hydroxypyrene (1-OHP). The estimated glomerular filtration rate (eGFR) was calculated using the Taiwanese Chronic Kidney Disease Epidemiology Collaboration equation, and the chronic kidney disease (CKD) prevalence and risks were defined according to KDIGO 2012 guidelines. Adjusted generalized linear and logistic regression models were applied to evaluate the associations between petrochemical exposure and renal functions. RESULTS: Subjects in the HE areas had significantly lower eGFR, higher CKD prevalence, and higher levels of urinary arsenic, cadmium, mercury, thallium and 1-OHP. The closer to complex and high exposure group of study subjects were significantly associated with the decrease in eGFR, higher ORs for CKD and high-intermediate risk of CKD. In addition, the study subjects who had two-fold urinary arsenic and 1-OHP levels were significantly with decreased 0.68 and 0.49 ml/min/1.73 m2 of eGFR, respectively. CONCLUSIONS: Residing closer and higher arsenic and polycyclic aromatic hydrocarbon exposure were associated with the renal impairment and risks of CKD among the residential population near the petrochemical industry.

Metabolomics of Children and Adolescents Exposed to Industrial Carcinogenic Pollutants.

Studies on metabolomes of carcinogenic pollutants among children and adolescents are limited. We aim to identify metabolic perturbations in 107 children and adolescents (aged 9-15) exposed to multiple carcinogens in a polluted area surrounding the largest petrochemical complex in Taiwan. We measured urinary concentrations of eight carcinogen exposure biomarkers (heavy metals and polycyclic aromatic hydrocarbons (PAHs) represented by 1-hydroxypyrene), and urinary oxidative stress biomarkers and serum acylcarnitines as biomarkers of early health effects. Serum metabolomics was analyzed using a liquid chromatography mass spectrometry-based method. Pathway analysis and "meet-in-the-middle" approach were applied to identify potential metabolites and biological mechanisms linking carcinogens exposure with early health effects. We found 10 potential metabolites possibly linking increased exposure to IARC group 1 carcinogens (As, Cd, Cr, Ni) and group 2 carcinogens (V, Hg, PAHs) with elevated oxidative stress and deregulated serum acylcarnitines, including inosine monophosphate and adenosine monophosphate (purine metabolism), malic acid and oxoglutaric acid (citrate cycle), carnitine (fatty acid metabolism), and pyroglutamic acid (glutathione metabolism). Purine metabolism was identified as the possible mechanism affected by children and adolescents' exposure to carcinogens. These findings contribute to understanding the health effects of childhood and adolescence exposure to multiple industrial carcinogens during critical periods of development.

Cluster analysis of fine particulate matter (PM2.5) emissions and its bioreactivity in the vicinity of a petrochemical complex.

This study evaluated associations between the bioreactivity of PM2.5in vitro and emission sources in the vicinity of a petrochemical complex in Taiwan. The average PM2.5 was 30.2 µg/m3 from 9 February to 23 March 2016, and the PM2.5 was clustered in long-range transport (with major local source) (12.8 µg/m3), and major (17.3 µg/m3) and minor industrial emissions (4.7 µg/m3) using a k-means clustering model. A reduction in cell viability and increases in the cytotoxicity-related lactate dehydrogenase (LDH), oxidative stress-related 8-isoprostane, and inflammation-related interleukin (IL)-6 occurred due to PM2.5 in a dose-dependent manner. The PM2.5 from major industrial emissions was significantly correlated with increased 8-isoprostane and IL-6, but this was not observed for long-range transport or minor industrial emissions. The bulk metal concentration was 9.52 ng/m3 in PM2.5. We further observed that As, Ba, Cd, and Se were correlated with LDH in the long-range transport group. Pb in PM2.5 from the major industrial emissions was correlated with LDH, whereas Pb and Se were correlated with 8-isoprostane. Sr was correlated with cell viability in the minor industrial emissions group. We demonstrated a new approach to investigate particle bioreactivity, which suggested that petrochemical-emitted PM2.5 should be a concern for surrounding residents' health.

Increased cancer incidence of Changhua residents living in Taisi Village north to the No. 6 Naphtha Cracking Complex.

BACKGROUND/PURPOSE: Cancer risks of residents living north to the No. 6 Naphtha Cracking Complex has not been studied before. METHODS: Our study subjects were recruited in 2014-16 from three zones north to the No. 6 Naphtha Cracking Complex, which included 229 participants from the Taisi Village (average 5.5 km from the complex), 1333 participants from the other 14 villages in Dacheng Township (9.2 km), and 372 participants from the Zhutang Township (19.9 km). Their occurrence of cancer in years-post-complex-operation (YPO) was defined by having a new cancer recorded (ICD-9: 140-208) in National Health Insurance Research Database since 1999. Poisson regression was conducted to compare incidence rate ratio among three zones in 10-16 YPO. RESULTS: We found that all-cause cancer incidence of 10-16 YPO (per 1,000 person-years) in Taisi Village (8.44) was higher than that in Dacheng (3.42) and Zhutang (2.72). Taisi residents had significantly higher concentrations of V, Cr, Mn, Ni, Cu, As, Cd, and Tl than Dacheng and Zhutang residents. The all-cause cancer incidence rate ratio between 10-16 and 0-9 YPO was 8.44 for Taisi residents. All-cause cancer incidence rate of Taisi residents was 2.55 times higher than Dacheng residents (95% CI: 1.89-3.45) and 2.43 times higher than Zhutang residents (95% CI: 1.54-3.84) in 10-16 YPO. CONCLUSION: We conclude that all-cause cancer risk was significantly increased for Taisi residents living near the No. 6 Naphtha Cracking Complex for 10-16 years after the complex began operating.

Increased cancers among residents living in the neighborhood of a petrochemical complex: A 12-year retrospective cohort study.

This study investigates whether cancers are increased for residents living in the vicinity of a petrochemical complex with coal power plants and refineries. We recruited a residential cohort of 2388 long-term residents aged above 35 years in 2009-2012 who lived within a 40 km radius of the complex. We measured their internal exposure biomarkers of urinary carcinogenic metals and retrospectively compared cancer incidences between those who lived fewer than 10 km from the complex (high exposure, HE) and those who lived more than 10 km from the complex (low exposure, LE). Residents had lived in their respective areas for 12 years, since the complex began operating in mid-1999. This included two periods of operation: 0-9 years and 10-12 years. Crude cumulative incident rates (CIRs) of all cancers were calculated for new cancer cases (ICD-9: 140-165, 170-176, 179-208) recorded in the Taiwan Health Insurance Database over total person-years at risk in each study period. Poisson regression was applied to estimate relative risks for the CIRs of all cancers between HE and LE areas during the 10-12 years since the beginning of the complex's operation, adjusting for age, gender, body mass index, smoking, hepatitis C, and occupational exposure. We found that our study subjects in HE areas had higher urinary carcinogenic metal levels, including As, Cd, Hg, Pb, and V, and higher prevalence rates of hepatitis C than those in LE areas. After the complex had been operating for 10-12 years, SIRs per 1000 person-years for all cancers in HE and LE areas were 4.44 vs. 2.48 for all subjects, 15.2 vs. 4.86 for elder subjects aged above 60 years, and 2.94 vs. 2.71 for female subjects. Correspondingly, the adjusted relative risks of CIRs for all cancers between HE and LE areas were 1.29 (95% CI: 0.99-1.68) for all subjects, 1.52 (1.04-2.22) for elder subjects, 1.41 (1.00-1.97) for female subjects, and 1.91 (1.15-3.19) for female elderly subjects. We conclude that elder and female residents living within 10 km of a petrochemical complex had higher carcinogenic exposure and cancers than those living farther away from the complex after the complex had been operating for 10 years.

Linking sources to early effects by profiling urine metabolome of residents living near oil refineries and coal-fired power plants.

BACKGROUND: This study aims at identifying metabolic changes linking external exposure to industrial air toxics with oxidative stress biomarkers. METHODS: We classified 252 study subjects as 111 high vs. 141 low exposure subjects by the distance from their homes to the two main emission sources, oil refineries and coal-fired power plants. We estimated individual's external exposure to heavy metals and polycyclic aromatic hydrocarbons (PAHs) by dispersion and kriging models, respectively. We measured urinary levels of heavy metals and 1-hydroxypyrene (1-OHP) as biomarkers of internal exposure, and 8-OHdG, HNE-MA, 8-isoPGF2α, and 8-NO2Gua as biomarkers of early health effects. We used two-dimensional gas chromatography time-of-flight mass spectrometry to identify urine metabolomics. We applied "meet-in-the-middle" approach to identify potential metabolites as putative intermediate biomarkers linking multiple air toxics exposures to oxidative stress with plausible exposures-related pathways. RESULTS: High exposure subjects showed elevated ambient concentrations of vanadium and PAHs, increased urine concentrations of 1-OHP, vanadium, nickel, copper, arsenic, strontium, cadmium, mercury, and thallium, and higher urine concentrations of all four urine oxidative stress biomarkers compared to low exposure subjects. We identified a profile of putative intermediate biomarkers that were associated with both exposures and oxidative stress biomarkers in participants. Urine metabolomics identified age-dependent biological pathways, including tryptophan metabolism and phenylalanine metabolism in children subjects (aged 9-11), and glycine, serine, and threonine metabolism in elderly subjects (aged>55), that could associate multiple exposures with oxidative stress. CONCLUSION: By profiling urine biomarkers and metabolomics in children and elderly residents living near a petrochemical complex, we can link their internal exposure to oxidative stress biomarkers through biological pathways associated with common complex chronic diseases and allergic respiratory diseases. The internal exposure may possibly be traced to multiple air toxics emitted from specific sources of oil refineries and coal-fired power plants.