Metal and oxidative potential exposure through particle inhalation and oxidative stress biomarkers: a 2-week pilot prospective study among Parisian subway workers.

OBJECTIVE: In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field. METHODS: We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2'deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times. RESULTS: The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDAEBC generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day. CONCLUSION: Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter.

Malondialdehyde and anion patterns in exhaled breath condensate among subway workers.

BACKGROUND: Underground transportation systems can contribute to the daily particulates and metal exposures for both commuter and subway workers. The redox and metabolic changes in workers exposed to such metal-rich particles have yet to be characterized. We hypothesize that the distribution of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) are modified depending on exposures. RESULTS: Particulate number and size as well as mass concentration and airborne metal content were measured in three groups of nine subway workers (station agents, locomotive operators and security guards). In parallel, pre- and post-shift EBC was collected daily during two consecutive working weeks. In this biological matrix, malondialdehyde, lactate, acetate, propionate, butyrate, formate, pyruvate, the sum of nitrite and nitrate (ΣNOx) and the ratio nitrite/nitrate as well as metals and nanoparticle concentrations was determined. Weekly evolution of the log-transformed selected biomarkers as well as their association with exposure variables was investigated using linear mixed effects models with the participant ID as random effect. The professional activity had a strong influence on the pattern of anions and malondialdehyde in EBC. The daily number concentration and the lung deposited surface area of ultrafine particles was consistently and mainly associated with nitrogen oxides variations during the work-shift, with an inhibitory effect on the ΣNOx. We observed that the particulate matter (PM) mass was associated with a decreasing level of acetate, lactate and ΣNOx during the work-shift, suggestive of a build-up of these anions during the previous night in response to exposures from the previous day. Lactate was moderately and positively associated with some metals and with the sub-micrometer particle concentration in EBC. CONCLUSIONS: These results are exploratory but suggest that exposure to subway PM could affect concentrations of nitrogen oxides as well as acetate and lactate in EBC of subway workers. The effect is modulated by the particle size and can correspond to the body's cellular responses under oxidative stress to maintain the redox and/or metabolic homeostasis.

Probable aerosol transmission of SARS-CoV-2 in a poorly ventilated courtroom.

There is increasing evidence of SARS-CoV-2 transmission via aerosol; the number of cases of transmission via this route reported in the literature remains however limited. This study examines a case of clustering that occurred in a courtroom, in which 5 of the 10 participants were tested positive within days of the hearing. Ventilation loss rates and dispersion of fine aerosols were measured through CO2 injections and lactose aerosol generation. Emission rate and influencing parameters were then computed using a well-mixed dispersion model. The emission rate from the index case was estimated at 130 quanta h-1 (interquartile (97-155 quanta h-1 ). Measured lactose concentrations in the room were found relatively homogenous (n = 8, mean 336 µg m-3 , SD = 39 µg m-3 ). Air renewal was found to play an important role for event durations greater than 0.5 h and loss rate below 2-3 h-1 . The estimated emission rate suggests a high viral load in the index case and/or a high SARS-CoV-2 infection coefficient. High probabilities of infection in similar indoor situations are related to unfavorable conditions of ventilation, emission rate, and event durations. Source emission control appears essential to reduce aerosolized infection in events lasting longer than 0.5 h.

Analytical techniques for multiplex analysis of protein biomarkers.

INTRODUCTION: The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research. AREAS COVERED: We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses. EXPERT COMMENTARY: The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine.

Site-directed introduction of disulfide groups on antibodies for highly sensitive immunosensors.

The interface between the sample and the transducer surface is critical to the performance of a biosensor. In this work, we compared different strategies for covalent self-assembly of antibodies onto bare gold substrates by introducing disulfide groups into the immunoglobulin structure, which acted as anchor molecules able to chemisorb spontaneously onto clean gold surfaces. The disulfide moieties were chemically introduced to the antibody via the primary amines, carboxylic acids, and carbohydrates present in its structure. The site-directed modification via the carbohydrate chains exhibited the best performance in terms of analyte response using a model system for the detection of the stroke marker neuron-specific enolase. SPR measurements clearly showed the potential for creating biologically active densely packed self-assembled monolayers (SAMs) in a one-step protocol compared to both mixed SAMs of alkanethiol compounds and commercial immobilization layers. The ability of the carbohydrate strategy to construct an electrochemical immunosensor was investigated using electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) transduction. Graphical Abstract Left: Functionalization strategies of bare gold substrates via direct bio-SAM using disulfide-containing antibody chemically modified via their primary amines (A), carbohydrates (B) and carboxylic acids (C). Right: Dependence of the peak height with NSE concentration at NSE21-CHO modified electrochemical immunosensor. Inset: Logarithmic calibration plot.

Increase in oxidative stress levels following welding fume inhalation: a controlled human exposure study.

BACKGROUND: Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. METHODS: Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H2O2), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. RESULTS: Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H2O2 concentrations ([95%CI: 4 % to 46 %], p = 0.01); a 91 % increase in urinary-H2O2 ([2 % to 258 %], p = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure (p = 0.01). CONCLUSION: A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is recommended that additional exposure metrics such as PNC are considered for occupational risk assessments. Our findings highlight the importance of increasing awareness of TIG welding fume toxicity, especially given the realities of welding workplaces that may lack ventilation; and beliefs among interviewed welders that TIG represents a cleaner and safer welding process.

Long-term exposure to PM10 and respiratory health among Parisian subway workers.

Exposure to ambient PM10 may increase the risk of chronic obstructive pulmonary disease (COPD) and lung function decline. We evaluated the long-term exposure to PM10 and its relationship with COPD prevalence and lung function in Parisian subway workers. Participants were randomly selected from a 15,000-subway worker cohort. Individual annual external exposure to PM10 (ePM10) was estimated using a company-specific job-exposure-matrix based on PM10 measurements conducted between 2004 and 2019 in the Parisian subway network. Mean annual inhaled PM10 exposure (iPM10) was modeled as function of ePM10 exposure, inhalation rate, and filtration efficiency of the respiratory protection used. COPD diagnosis was performed in March-May 2021 based on post-bronchodilator spirometry. The relationship between iPM10 and outcomes was assessed using logistic and linear regression models, adjusted for exposure duration and potential confounders. Amongst 254 participants with complete data, 17 were diagnosed as COPD. The mean employment duration was 23.2 ± 7.3years, with annual mean ePM10 of 71.8 ± 33.7 µg/m3 and iPM10 of 0.59 ± 0.27 µg/shift, respectively. A positive but statistically non-significant association was found for COPD prevalence with iPM10 (OR = 1.034, 95%-CI = 0.781; 1.369, per 100 ng/shift) and ePM10 (OR = 1.029, 95%-CI = 0.879; 1.207, per 10 µg/m3). No decline in lung function was associated with PM10 exposure. However, forced expiratory volume during the first second and forced vital capacity lower than normal were positively associated with exposure duration (OR = 1.125, 95%-CI = 1.004; 1.260 and OR = 1.171, 95%-CI = 0.989; 1.386 per year, respectively). Current smoking was strongly associated with COPD prevalence (OR = 6.85, 95%-CI = 1.87; 25.10) and most lung function parameters. This is the first study assessing the relationship between long-term exposure to subway PM10 and respiratory health in subway workers. The risk estimates related with subway PM10 exposure are compatible with those related to outdoor PM10 exposure in the large recent studies. Large cohorts of subway workers are necessary to confirm these findings.

Discriminative potential of exhaled breath condensate biomarkers with respect to chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affecting 334 million people in the world remains a major cause of morbidity and mortality. Proper diagnosis of COPD is still a challenge and largely solely based on spirometric criteria. We aimed to investigate the potential of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) to discriminate COPD patients. METHODS: Three hundred three participants were randomly selected from a 15,000-transit worker cohort within the Respiratory disease Occupational Biomonitoring Collaborative Project (ROBoCoP). COPD was defined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second to Forced Vital Capacity < 0.7 in spirometry validated by an experienced pulmonologist. Discriminative power of biomarker profiles in EBC was analyzed using linear discriminant analyses. RESULTS: Amongst 300 participants with validated spirometry, 50.3% were female, 52.3 years old in average, 36.0% were current smokers, 12.7% ex-smokers with mean tobacco exposure of 15.4 pack-years. Twenty-one participants (7.0%) were diagnosed as COPD, including 19 new diagnoses, 12 of which with a mild COPD stage (GOLD 1). Amongst 8 biomarkers measured in EBC, combination of 2 biomarkers, Lactate and Malondialdehyde (MDA) significantly discriminated COPD subjects from non-COPD, with a 71%-accuracy, area under the receiver curve of 0.78 (p-value < 0.001), and a negative predictive value of 96%. CONCLUSIONS: These findings support the potential of biomarkers in EBC, in particular lactate and MDA, to discriminate COPD patients even at a mild or moderate stage. These EBC biomarkers present a non-invasive and drugless technique, which can improve COPD diagnosis in the future.

Job Exposure Matrix, a Solution for Retrospective Assessment of Particle Exposure in a Subway Network and Their Long-Term Effects.

INTRODUCTION: Health effects after long-term exposure to subway particulate matter (PM) remain unknown due to the lack of individual PM exposure data. This study aimed to apply the job exposure matrix (JEM) approach to retrospectively assess occupational exposure to PM in the Parisian subway. METHODS: Job, the line and sector of the transport network, as well as calendar period were four JEM dimensions. For each combination of these dimensions, we generated statistical models to estimate the annual average PM10 concentration using data from an exhaustive inventory of the PM measurement campaigns conducted between 2004 and 2020 in the Parisian subway and historical data from the Parisian air pollution monitoring network. The resulting JEM and its exposure estimates were critically examined by experts using the uncertainty analysis framework. RESULTS: The resulting JEM allows for the assignment of the estimated annual PM10 concentration to three types of professionals working in the subway: locomotive operators, station agents, and security guards. The estimates' precision and validity depend on the amount and quality of PM10 measurement data used in the job-, line-, and sector-specific models. Models using large amounts of personal exposure measurement data produced rather robust exposure estimates compared to models with lacunary data (i.e., in security guards). The analysis of uncertainty around the exposure estimates allows for the identification of the sources of uncertainty and parameters to be addressed in the future in order to refine and/or improve the JEM. CONCLUSIONS: The JEM approach seems relevant for the retrospective exposure assessment of subway workers. When applied to available data on PM10, it allows for the estimation of this exposure in locomotive operators and station agents with an acceptable validity. Conversely, for security guards, the current estimates have insufficient validity to recommend their use in an epidemiological study. Therefore, the current JEM should be considered as a valid prototype, which shall be further improved using more robust measurements for some jobs. This JEM can also be further refined by considering additional exposure determinants.

Repeated Human Exposure to Semivolatile Organic Compounds by Inhalation: Novel Protocol for a Nonrandomized Study.

BACKGROUND: Semivolatile organic compounds (SVOCs) comprise several different chemical families used mainly as additives in many everyday products. SVOCs can be released into the air as aerosols and deposit on particulate matter during use by dispersion, evaporation, or abrasion. Phthalates are SVOCs of growing concern due to their endocrine-disrupting effects. Human data on the absorption, distribution, metabolism, and excretion (ADME) of these compounds upon inhalation are almost nonexistent. OBJECTIVE: The goal of this study is to develop a method for repeated inhalation exposures to SVOCs to characterize their ADME in humans. METHODS: We will use diethylhexyl phthalate (DEHP), a major indoor air pollutant, as a model SVOC in this novel protocol. The Swiss official Commission on Ethics in Human Research, Canton de Vaud, approved the study on October 14, 2020 (project-ID 2020-01095). Participants (n=10) will be repeatedly exposed (2 short daily exposures over 4 days) to isotope-labeled DEHP (DEHP-d4) to distinguish administered exposures from background exposures. DEHP-d4 aerosols will be generated with a small, portable, aerosol-generating device. Participants will inhale DEHP-d4-containing aerosols themselves with this device at home. Air concentrations of the airborne phthalates will be less than or equal to their occupational exposure limit (OEL). DEHP-d4 and its metabolites will be quantified in urine and blood before, during, and after exposure. RESULTS: Our developed device can generate DEHP-d4 aerosols with diameters of 2.5 µm or smaller and a mean DEHP-d4 mass of 1.4 (SD 0.2) µg per puff (n=6). As of May 2023, we have enrolled 5 participants. CONCLUSIONS: The portable device can be used to generate phthalate aerosols for repeated exposure in human studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51020.

Occupational exposure to nanomaterials and biomarkers in exhaled air and urine: Insights from the NanoExplore international cohort.

The current evidence on nanomaterial toxicity is mostly derived from experimental studies making it challenging to translate it into human health risks. We established an international cohort (N = 141 workers) within the EU-LIFE project "NanoExplore" to address possible health effects from occupational exposures to nanomaterials. We used a handheld direct-reading optical particle counter to measure airborne nanoparticle number concentrations (PNC) and lung-deposited surface areas (LDSAs). Airborne particles were characterized by TEM and SEM-EDAX. We assessed oxidative/nitrosative stress with a panel of biomarkers in exhaled breath condensate (EBC) (8-isoprostane, malondialdehyde, nitrotyrosine), inflammation (high-sensitivity C reactive protein (hs-CRP), IL-1ß, TNF-α, IL-10) and KL-6 (considered as biomarker of interstitial lung fibrosis) and urine (total antioxidant power (TAP), 8-isoprostane, and malondialdehyde). Exhaled breath sampled in gas-sampling bags were assessed for oxidative potential. These biomarkers were quantified pre-shift at the beginning of the workweek and post-shift the 4th day. Relationships between airborne nanoparticle concentration and biomarkers were assessed by multiple linear regression with log-transformed exposure and biomarker concentrations adjusted for potential confounders. We found a positive dose-response relationship for three inflammation biomarkers (IL-10, IL-1ß and TNF-α) in EBC with both PNC and LDSA. A negative dose-response relationship was observed between PNC and TAP. This study suggests that occupational exposures to nanoparticles can affect the oxidative balance and the innate immunity in occupationally exposed workers. However, owing to the intrinsic variability of biomarkers, the observed changes along with their health significance should be assessed in a long-term perspective study.

A harmonized protocol for an international multicenter prospective study of nanotechnology workers: the NanoExplore cohort.

Nanotechnology applications are fast-growing in many industrial fields. Consequently, health effects of engineered nanomaterials (ENMs) should be investigated. Within the EU-Life project NanoExplore, we developed a harmonized protocol of an international multicenter prospective cohort study of workers in ENM-producing companies. This article describes the development of the protocol, sample size calculation, data collection and management procedures and discusses its relevance with respect to research needs. Within this protocol, workers' ENM exposure will be assessed over four consecutive working days during the initial recruitment campaign and the subsequent follow-up campaigns. Biomonitoring using noninvasive sampling of exhaled breath condensate (EBC), exhaled air, and urine will be collected before and after 4-day exposure monitoring. Both exposure and effect biomarkers, will be quantified along with pulmonary function tests and diagnosed diseases reported using a standardized epidemiological questionnaire available in four languages. Until now, this protocol was implemented at seven companies in Switzerland, Spain and Italy. The protocol is well standardized, though sufficiently flexible to include company-specific conditions and occupational hygiene measures. The recruitment, to date, of 140 participants and collection of all data and samples, enabled us launching the first international cohort of nanotechnology workers. All companies dealing with ENMs could join the NanoExplore Consortium, apply this harmonized protocol and enter in the cohort, concieved as an open cohort. Its protocol meets all requirements of a hypotheses-driven prospective study, which will assess and reassess effects of ENM exposure on workers' health by updating the follow-up of the cohort. New hypothesis could be also considered.

Challenges in Quantifying 8-OHdG and 8-Isoprostane in Exhaled Breath Condensate.

Exhaled breath condensate (EBC) has attracted substantial interest in the last few years, enabling the assessment of airway inflammation with a non-invasive method. Concentrations of 8-Hydroxydesoxyguanosine (8-OHdG) and 8-isoprostane in EBC have been suggested as candidate biomarkers for lung diseases associated with inflammation and oxidative stress. EBC is a diluted biological matrix and consequently, requires highly sensitive chemical analytic methods (picomolar range) for biomarker quantification. We developed a new liquid chromatography coupled to tandem mass spectrometry method to quantify 8-OHdG and 8-isoprostane in EBC simultaneously. We applied this novel biomarker method in EBC obtained from 10 healthy subjects, 7 asthmatic subjects, and 9 subjects with chronic obstructive pulmonary disease. Both biomarkers were below the limit of detection (LOD) despite the good sensitivity of the chemical analytical method (LOD = 0.5 pg/mL for 8-OHdG; 1 pg/mL for 8-isoprostane). This lack of detection might result from factors affecting EBC collections. These findings are in line with methodological concerns already raised regarding the reliability of EBC collection for quantification of 8-OHdG and 8-isoprostane. Precaution is therefore needed when comparing literature results without considering methodological issues relative to EBC collection and analysis. Loss of analyte during EBC collection procedures still needs to be resolved before using these oxidative stress biomarkers in EBC.

Measuring Short-Term Exposures to H2O2 Among Exposed Workers; A Feasibility Study.

Hydrogen peroxide (H2O2) is a strong oxidizing agent often used in hair coloring and as a component in disinfecting and bleaching processes. Exposures to H2O2 generate reactive oxygen species (ROS) that can cause significant airway irritation and inflammation. Even though workers have reported symptoms associated with sensitivity and irritation from acute exposures below the H2O2 occupational exposure levels (OELs), a lack of sensitive analytical methods for measuring airborne concentrations currently prevents evaluating low or peak H2O2 exposures. To fill these gaps, we propose two different sensitive approaches: (i) luminol chemiluminescence (CL) to specifically measure H2O2; and (ii) photonic sensor method based on the ferrous-xylenol orange assay to evaluate total oxidative potential (OP), a measure of ROS in sampled air. We chose two exposure scenarios: hairdressers preparing and applying hair color to clients (both in simulated and field environments) and workers operating disinfecting cycles at a bottling company. Hair coloring took about 1 h for each client, and the application of the coloring product generated the highest H2O2 concentrations. OP values were highly correlated with H2O2 concentrations (CL measurement) and allowed peak measurements as low as 6 µg m-3 of H2O2 concentrations. The bottling company used a disinfectant containing H2O2, acetic acid and peracetic acid (PAA) in an enclosed process. The photonic sensor was immediately saturated. The CL results showed that the process operator had the highest exposures during a 15-min cycle. There is still a need to develop these direct reading methods for operating in the field, but we believe that in the future an OEL for OP could protect workers from developing airway irritation and inflammation by reducing exposures to oxidizing chemicals.

A Real-Time Comparison of Four Particulate Matter Size Fractions in the Personal Breathing Zone of Paris Subway Workers: A Six-Week Prospective Study.

We developed a Bayesian spline model for real-time mass concentrations of particulate matter (PM10, PM2.5, PM1, and PM0.3) measured simultaneously in the personal breathing zone of Parisian subway workers. The measurements were performed by GRIMM, a gravimetric method, and DiSCmini during the workers' work shifts over two consecutive weeks. The measured PM concentrations were analyzed with respect to the working environment, the underground station, and any specific events that occurred during the work shift. Overall, PM0.3 concentrations were more than an order of magnitude lower compared to the other PM concentrations and showed the highest temporal variation. The PM2.5 levels raised the highest exposure concern: 15 stations out of 37 had higher mass concentrations compared to the reference. Station PM levels were not correlated with the annual number of passengers entering the station, the year of station opening or renovation, or the number of platforms and tracks. The correlation with the number of station entrances was consistently negative for all PM sizes, whereas the number of correspondence concourses was negatively correlated with PM0.3 and PM10 levels and positively correlated with PM1 and PM2.5 levels. The highest PM10 exposure was observed for the station platform, followed by the subway cabin and train, while ticket counters had the highest PM0.3, PM1, and PM2.5 mass concentrations. We further found that compared to gravimetric and DiSCmini measurements, GRIMM results showed some discrepancies, with an underestimation of exposure levels. Therefore, we suggest using GRIMM, calibrated by gravimetric methods, for PM sizes above 1µm, and DiSCmini for sizes below 700 nm.

Oxidative Potential in Exhaled Air (OPEA) as a Tool for Predicting Certain Respiratory Disorders in the General Adult Population: Cross-Sectional Analysis Nested in the Swiss Health Study.

In a pilot clinical study, OPEA allowed for distinguishing participants with and without chronic obstructive pulmonary disease. This study aimed to assess whether abnormal spirometry parameters and immunity against SARS-CoV-2 are associated with increased OPEA and estimating the OPEA reference interval. Swiss adult residents of the Vaud Canton aged 20-69 years randomly selected from the Federal Statistical Office's registries, speaking French or German, were included and examined between 1 October 2020 and 31 December 2021. General health status and presence of respiratory diseases were assessed by questionnaire and spirometry. Spirometric results were compared with the predicted values and their lower limits of norms of the Global Lung Function Initiative. SARS-CoV-2-seroprevalence was assessed using the Luminex-based test of IgG. Statistical analysis consisted of unilateral t-tests and ANOVA. Lower and upper limit of OPEA reference interval with associated 90%-confidence interval (90%CI) were estimated for the sub-sample of healthy adults by bootstrap, after excluding outliers. The study sample included 247 participants. SARS-CoV-2-seropositive participants and those with an obstructive syndrome had a significantly higher OPEA than seronegative and healthy participants. The estimated reference interval was: -0.0516 (90%CI = -0.0735; -0.0316); -0.0044 (90%CI = -0.0224; 0.0153). OPEA could predict inflammatory-based respiratory disorders, but needs further validation in different settings and for other pathologies.

A proposed synergetic mechanism for metal fume fever involving ZnO and Fe3O4 nanoparticles.

Metal fumes fever (MFF) is an inflammatory condition, whose mechanism is yet unclear, associated with the inhalation of metal fumes, particularly zinc. In this study we investigate experimentally the hypothesis of a two-step mechanism of MFF onset: (1) the photocatalytic production of airborne hydrogen peroxide (H2O2) via ZnO and (2) the production of hydroxyl radicals (HOׄ) through Fenton reaction via magnetite (Fe3O4) nanoparticles. Photocatalysis and Fenton reaction products were measured using a multiscattering-enhanced absorbance device and assessing the degradation of bromophenol blue with microplate photometry, respectively. We observed that in the presence of UV, ZnO produces 3 to 4-times more H2O2 than UV alone or that non-UV irradiated ZnO. In the presence of biologically-relevant ligands, we also measured a Fenton reaction at physiological pH with either Fe(II), Fe(III) or Fe3O4 nanoparticles. Our results support the hypothesis of a two-step mechanism of MFF onset, in which the prior presence of Fe in the lungs exacerbates the oxidative stress, triggered by the photocatalysis of ZnO, a situation that could occurs when welding galvanized steel. More broadly, this raises the question of the role of the Fenton mechanism in respiratory exposure to metal particles and its possible contribution to other lung diseases.

Method Validation and Characterization of the Associated Uncertainty for Malondialdehyde Quantification in Exhaled Breath Condensate.

There are several methods for quantifying malondialdehyde (MDA), an oxidative stress biomarker, in exhaled breath condensate (EBC). However, due to the very diluted nature of this biological matrix, a high variability is observed at low concentrations. We aimed to optimize a 2,4-dinitrophenylhydrazine-based method using liquid chromatography coupled to tandem mass spectrometry and characterize the uncertainty associated with this method. We investigated the following parameters for the method validation: calibration linearity, limit of detection (LOD), precision, recovery, and matrix effect. The results were used to identify the main sources of uncertainty and calculating the combined uncertainty. The applicability of this method was evaluated in an ongoing epidemiological study by analyzing 164 EBC samples collected from different professional groups in subway environments. The optimized method was sensitive (LOD: 70 pg/mL), precise (inter-day variation < 19%) and accurate (recovery range: 92-106.5%). The calculated analytical uncertainty was the highest at the LOQ level and reached 23%. Although the analytical uncertainty was high at low MDA concentrations, it was significantly lower than that the observed inter-individual variability. Hence, this method performs sufficiently well and can be recommended for future use in epidemiological researches relying on between-subject differences.

Oxidative potential of aerosolized metalworking fluids in occupational settings.

The oxidative potential (OP) measures the ability of pollutants to oxidize a chemical/biological probe. Such assays are starting to gain acceptance as integrative exposure metrics associated with inflammatory-based pathologies. Diseases such as asthma, rhinitis or cancers are reported for workers exposed to oil mist, which are aerosols of metal working fluids (MWF) emitted during the machining of metals. Measuring oil mist in the air is challenging, and exposures are often quantified as the mass fraction, which does not account for exposures to the gaseous fraction. Consequently, exposures are underestimated and furthermore, the hazardous property of oil mist is not assessed. We postulate that it is more relevant to assess occupational exposures to the hazardous fractions of oil mist by measuring OP than by simply measuring mass. We characterized exposures to straight and water-based MWF among workers in the French and Swiss mechanical industry using standard methods for oil mist and the ferrous orange xylenol assay for OP assessment (OPFOX). Considering the particulate fraction, the water-based MWF presented the greatest OPFOX. The OP was associated with organic carbon and iron content. The gaseous fraction of the oil mist presented also an important redox activity, particularly in workshops where straight oils were used. The hexanal concentration was associated with this OPFOX. The OPFOX measurement is thus integrative of multiple parameters, and bring complementary information when assessing MWF exposures. Our results highlight that OPFOX account for MWF type and could be an interesting parameter to characterize such exposure.