Follow-up of the manganese-exposed workers healthy cohort (MEWHC) and biobank management from 2011 to 2017 in China.

BACKGROUND: Long-term excess exposure to environmental manganese (Mn) can lead to multi-system damage, especially in occupational populations. Therefore, we established a manganese-exposed workers healthy cohort (MEWHC), focusing on the systemic health effects related to Mn exposure. Here, we aimed to describe the follow-up activity for the MEWHC study and establish a standardized biological sample bank for the scientific management of high-quality biospecimens and the attached data from 2011 to 2017. METHODS: Baseline examinations for onsite workers were conducted, and the biobank for the MEWHC was first established in 2011; follow-up examinations occurred four times between July 2012 and November 2017. All questionnaires, clinical data and biological samples were routinely collected during each follow-up activity. Additional workers were recruited in 2016, which further enriched the resources of the biobank. RESULTS: A total of 2359 onsite workers and 612 retired workers at a ferromanganese refinery were enrolled in the prospective cohort, and their biological samples were obtained in the preliminary baseline survey and the follow-up investigation, including 2971 blood and urine samples from the cohort. In addition, 1524 hair samples, 1404 nail (toe and finger nails) and 1226 fecal samples were also collected. All specimens were preserved in the biobank, and the data were scientifically managed using a computer system. CONCLUSIONS: The MEWHC study in China provides an effective way to obtain biological samples such as plasma, DNA, hair and urine for storage in a biobank for further study. The standardized management of various samples is crucial for accessing high-quality biospecimens.

Manganese in blood cells as an exposure biomarker in manganese-exposed workers healthy cohort.

Elevated exposure to manganese (Mn) has long been a public health concern. However, there is currently no consensus on the best exposure biomarker. Here we aimed to investigate the exposomic characteristics of plasma metals among Mn-exposed workers and explore the potential biomarkers of Mn exposure in the blood pool. First, total sixteen plasma metals (Calcium, Magnesium, Iron, Zinc, Copper, Selenium, Lead, Chromium, Arsenic, Manganese, Nickel, Molybdenum, Cadmium, Mercury, Thallium, and Cobalt) were determined among 40 occupationally Mn-exposed subjects. Second, Mn levels in both plasma and blood cells were detected among 234 workers from the manganese-exposed workers healthy cohort (MEWHC), respectively. Analysis of plasma metal exposome showed that the plasma Mn concentrations were positively correlated to plasma Fe (r=0.361), Ni (r=0.363), Cr (r=0.486), and Hg (r=0.313) (all p<0.05). Mn concentrations in plasma were not significantly correlated to external exposure levels (ptrend=0.200), and it was further confirmed among the 234 subjects (ptrend=0.452). However, Mn concentrations in blood cells progressively increased as the external exposure dose increased (low-exposure group vs high-exposure group, median 11.53µg/L vs 20.41µg/L, ptrend=0.001). Our results suggest that Mn in blood cells, but not plasma, could serve as a potential internal exposure biomarker. Larger validation studies are needed to establish the utility of this biomarker.

Synergistic impaired effect between smoking and manganese dust exposure on pulmonary ventilation function in Guangxi manganese-exposed workers healthy cohort (GXMEWHC).

PURPOSE: The aims of this study were to investigate the effects of manganese (Mn) dust exposure on lung functions and evaluate the potential synergistic effect between smoking and Mn dust exposure among refinery workers. METHODS: A retrospective study including 1658 workers in a ferromanganese refinery was conducted, with subjects who were from the Guangxi manganese-exposed workers healthy cohort (GXMEWHC). Based on the Mn manganese cumulative exposure index (Mn-CEI), all subjects were divided into the low exposure group (n = 682) and the high exposure group (n = 976). A pulmonary function test was performed using an electronic spirometer, including the values and percentages of FVC, FEV1, FEV1/FVC, MMEF, PEFR, MVV, respectively. RESULTS: No significant effect of Mn dust exposure on the pulmonary function was found in the female workers (all p>0.05). However, there was an obvious decrease in the male workers in the high exposure group compared with those in the low exposure group (FVC -60 ml, FEV1 -120 ml, MMEF -260 ml/s, MVV -5.06 L, all p<0.05). In the high exposure group, the reduction in FVC% predicted, MMEF and MMEF% predicted was 1.0%, 210 mL/s, and 4.9%, respectively. In particular, among the exposed subjects smokers had a statistically significant decrease in lung function compared with non-smokers and the reduction in FVC% predicted, MMEF and MMEF% predicted was 1.0%, 210 mL/s, and 4.9%, respectively (p<0.05). Partial correlation analysis showed that there was also negative correlation between Mn-CEI and decreased changes in MMEF (r = -0.159, p = 0.018) and also MMEF% predicted (r = -0.163, p = 0.015). CONCLUSIONS: Mn dust can impair the pulmonary ventilation function of male workers but not females, and individual smoking habits and manganese exposure had a synergistic effect on the lung function decrease.

Rationale, design and baseline results of the Guangxi manganese-exposed workers healthy cohort (GXMEWHC) study.

OBJECTIVE: To determine the relationship between biomarkers of exposure, disease and susceptibility, and early health effects and long-term diseases related to occupational manganese (Mn) exposure. DESIGN: Baseline survey of a longitudinal cohort study of workers in a ferromanganese refinery. PARTICIPANTS: A total of 1888 individuals (1197 men, 691 women; average seniority 15.34 years) were enrolled in the Guangxi manganese-exposed workers healthy cohort (GXMEWHC) study. Participants were between 18 and 60 years of age (mean 40.31 years), had worked in the ferromanganese refinery for at least 1 year and lived in the local area. RESULTS: The GXMEWHC study included a baseline survey. Participants were divided into four groups according to manganese (Mn) cumulative exposure index (Mn-CEI) levels: an internal control group (Mn-CEI <1.0 mg/m(3) year), a low exposure group (1.0 mg/m(3) year≤Mn-CEI<2.0 mg/m(3) year), a medium exposure group (2.0 mg/m(3) year≤Mn-CEI<5.0 mg/m(3) year) and a high exposure group (Mn-CEI≥5.0 mg/m(3) year). Genome-wide association studies of quantitative trait loci and binary trait loci in 500 Mn-exposed workers were performed using Illumina Infinium HumanExome BeadChip arrays. Stored plasma, DNA, hair and urine are available for further study. Participants will be followed up every 3 years. CONCLUSIONS: The GXMEWHC study provides abundant data for exploring the systemic health effects of occupational Mn exposure using biomarkers of exposure, disease and susceptibility.

Cognitive function and plasma BDNF levels among manganese-exposed smelters.

OBJECTIVES: To explore the potential dose-response relationship between manganese (Mn) exposure and cognitive function and also plasma brain-derived neurotrophic factor (BDNF) levels in occupational Mn exposure workers. METHODS: A total 819 workers were identified from our Mn-exposed workers, and 293 control workers were recruited in the same region. All exposed workers were divided into three groups based on Mn cumulative exposure index. The Montreal Cognitive Assessment (MoCA) test was applied to estimate cognitive function for all subjects. Plasma BDNF levels were determined by ELISA in 248 selected exposed workers and 100 controls. RESULTS: Mn-exposed workers had significantly lower MoCA scores than those in the control group (25.62 ± 0.25): those in high-exposure group had the lowest scores (21.33 ± 0.32), compared with the intermediate-exposure group (23.22 ± 0.30) and low-exposure group (23.57 ± 0.23). Mn exposure levels were inversely associated with MoCA total scores, all p<0.05. A positive correlation was found between plasma BDNF levels and MoCA total scores (r=0.278, p<0.01). Moreover, compared with the control group (288.7 ± 181.7 pg/mL), BDNF levels were lower in the high-exposure group (127.5 ± 99.8 pg/mL), and in the intermediate-exposure (178.2 ± 138.1 pg/mL) and low-exposure groups (223.4 ± 178.3 pg/mL). Additionally, plasma BDNF levels decreased significantly as Mn exposure levels increased (ptrend<0.01). CONCLUSIONS: Mn exposure may be associated with decreased plasma BDNF levels and cognition impairment in this large cross-sectional study.