Particle and metal exposure in Parisian subway: Relationship between exposure biomarkers in air, exhaled breath condensate, and urine.

Subway particulate toxicity results from in vitro and in vivo studies diverge and call for applied human research on outcomes from chronic exposures and potential exposure biomarkers. We aimed to (1) quantify airborne particulate matter (PM) concentrations (mass and number) and metal concentrations in exhaled breath condensate (EBC), urine, and PM; (2) investigate their associations (EBC vs. PM vs. urine); and (3) assess the relevance of EBC in biomonitoring. Nine subway workers in three jobs: station agents, locomotive operators and security guards were monitored during their 6-h shifts over two consecutive weeks. Six-hour weighed average mass concentrations expressed as PM10, PM2.5 and their metal concentrations were determined. Urine and EBC samples were collected pre- and post-shift. Ultrafine particle (UFP) number concentrations were quantified in PM and EBC samples. Metal concentrations in urine and EBC were standardized by creatinine and EBC volume, respectively, and log-transformed. Associations were investigated using Pearson correlation and linear mixed regression models, with participant's ID as random effect. PM concentrations were below occupational exposure limits (OEL) and varied significantly between jobs. Locomotive operators had the highest exposure (189 and 137 µg/m3 for PM10 and PM2.5, respectively), while station agents had the highest UFP exposure (1.97 × 104 particles/cm3). Five metals (Al, Fe, Zn, Cu, and Mn) in PM2.5 and three (Al, Fe, and Zn) in PM10 were above the limit of quantification (LOQ). Fe, Cu, Al and Zn were the most abundant by mass fraction in PM. In EBC, the metal concentrations in decreasing order were: Zn > Cu > Ni > Ba > Mn. Security guards had the highest EBC metal concentrations, and in particular Zn and Cu. Urinary metal concentrations in decreasing order were: Si > Zn > Mo > Ti > Cu > Ba ≈ Ni > Co. All urinary metal concentrations from the subway workers were similar to concentrations found in the general population. A statistically significant relationship was found for ultrafine particle number concentrations in PM and in EBC. Zn and Cu concentrations in post-shift EBC were associated with Zn and Cu concentrations in PM10 and with post-shift urinary Zn and Cu concentrations. Therefore, EBC appears a relevant matrix for assessing exposure to UFP in human biomonitoring when inhalation is a primary route of exposure. We found different temporal variation patterns between particle and metal exposures in three matrices (PM, urine, EBC) quantified daily over two full weeks in subway workers. These patterns might be related to metal oxidation, particulates' solubility and size as well as their lung absorption capabilities, which need to be further explored in toxicological research. Further research should also focus on understanding possible influences of low chronic exposures to subway particulates on health in larger cohorts.

Respiratory Disease Occupational Biomonitoring Collaborative Project (ROBoCoP): A longitudinal pilot study and implementation research in the Parisian transport company.

The ROBoCoP project is launched within the EU COST Action CA16113 "CliniMARK" aiming to increase the number of clinically validated biomarkers and focused on chronic obstructive pulmonary disease (COPD) biomarker development and validation. ROBoCoP encompasses two consecutive studies consisting of a pilot study followed by a field study. The pilot study is a longitudinal exposure assessment and biomarker study aiming at: 1-understanding the suitability of the candidate biomarkers in surveying populations at risk such as workers exposed to COPD causing agents; 2-determining the best sampling plan with respect to the half-life of the candidate biomarkers; 3-implementing and validating the sampling procedures and analytical methods; 4-selecting the best suitable biomarkers to be measured in the field. Each study participant is surveyed every day during the 6-8 h work-shifts for two consecutive weeks. The field study has an implementation research designe that enabled us to demonstrate the applicability of the standardized protocol for biomarker measurements in occupational settings while also assessing the biomarkers' validity. ROBoCoP will focus on particulate matter (PM) exposure measurements, exposure biomarkers and a series of effect biomarkers, including markers of lipoperoxidation: 8-isoprostane, malondialdehyd in exhaled breath condensate (EBC) and urine, potential markers of nitrosative stress: NO2-, NO3- and formate anion in EBC; markers of DNA oxidation: 8-hydroxy-2'deoxyguanosine in EBC and urine, marker of genotoxicity: micronuclei in buccal cells, and oxidative potential in exhaled air (OPEA). OPEA appears particularly promising as a clinical biomarker for detecting COPD, and will be tested independently and as part of a biomarker panel. COPD diagnosis will be performed by an experienced occupational physician according to international diagnostic standards and confirmed by a pulmonologist.This research will include approximatively 300 underground subway workers randomly selected from the personnel registry of a large Parisian transport company. Underground subways are suggested as the most PM polluted urban transport environment. We believe this occupational exposure is relevant for biomonitoring of workers and early detection of respiratory diseases.

Urinary 8-isoprostane as a biomarker for oxidative stress. A systematic review and meta-analysis.

Oxidative stress is defined as an imbalance between the production and elimination of reactive oxygen species (ROS) are associated with various inflammation-related human disease. ROS can oxidize lipids, which subsequently undergo fragmentation to produce F2-isoprostanes (F2-IsoPs). Eight-isoprostane is one of the most extensively studied F2-IsoPs and the most commonly used biomarker for the assessment of oxidative stress in human studies. This urinary biomarker is quantified using either chemical or immunological techniques. A "physiological" range for 8-isoprostanes is needed to use this biomarker as a measure of excess oxidative stress originating from occupational exposures. However, ranges reported in the literature are inconsistent. We designed a standardized protocol of a systematic review and meta-analysis to assess baseline values for 8-isoprostane concentrations in urine of healthy adults and identify determinants of their inter- and intra-individual variability. We searched PubMed from journal inception and up to April 2019, and screened articles for studies containing F2-IsoPs concentrations in urine for healthy adult participants. We grouped studies in three biomarker groups: "8-isoprostane", "Isoprostanes" "15- F2t-Isoprostane". We computed geometric mean (GM) and geometric standard deviation (GSD) as the basis for the meta-analysis. Of the initial 1849 articles retrieved, 63 studies were included and 107 subgroups within these study populations were identified. We stratified the subgroups analyzed with the chemical methods by body mass index (BMI) reported. We provide pooled GM values for urinary 8-isoprostane concentrations in healthy adults, separately for chemical and immunological analysis in this review. The interquartile range (IQR) in subgroups with a mean BMI below 25 measured using chemical methods was 0.18 to 0.40 µg/g creatinine. We show that there is a significant positive association between BMI and urinary 8-isoprostane concentrations. We recommend adjusting urinary 8-isoprostane concentrations in spot urine with creatinine, quantifying 8-isoprostane with chemical analytical methods, and reporting results as median and quartiles. This will help in comparing results across studies.

Reference ranges of oxidative stress biomarkers selected for non-invasive biological surveillance of nanotechnology workers: Study protocol and meta-analysis results for 8-OHdG in exhaled breath condensate.

In the field of engineered nanomaterials (ENMs) and other airborne particulate exposure biomonitoring, circulating oxidative stress biomarkers appear promising. These biomarkers could be monitored in different biological matrices. Exhaled breath condensate (EBC) enables their measurements in the respiratory tract, without affecting airway function or creating inflammation. The 8-hydroxy-2-deoxyguanosine (8-OHdG) was found increased in the EBC of ENM-exposed workers. Our objectives were to assess the reference range of 8-OHdG in the EBC and to identify determinants of its inter- and intra-individual variability. The meta-analysis was stratified by analytical method (chemical versus immunochemical analysis) and resulted in a between-study variability over 99 % of the total variability. The between-study variability completely dominated the within-studies variability. By using a mixed model with study ID as a random effect rather than a meta-regression, only smoking was evidenced as a potential determinant of 8-OHdG inter-individual variability, and only when immunochemical analysis was used. To our knowledge, this is the first meta-analysis aimed at estimating reference values for 8-OHdG in the EBC. The estimated values should be considered preliminary, as they are based on a limited number of studies, mostly of moderate to low quality of evidence. Further research is necessary to standardize EBC sampling, storage and analytical methods. Such a standardization would enable a more accurate estimation of the reference ranges of the 8-OHdG and potentially other biomarkers measurable in the EBC, which are essential for a meaningful interpretation of the biomonitoring results.