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.

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.

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.

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.

Reusability of filtering facepiece respirators after decontamination through drying and germicidal UV irradiation.

INTRODUCTION: During pandemics, such as the SARS-CoV-2, filtering facepiece respirators plays an essential role in protecting healthcare personnel. The recycling of respirators is possible in case of critical shortage, but it raises the question of the effectiveness of decontamination as well as the performance of the reused respirators. METHOD: Disposable respirators were subjected to ultraviolet germicidal irradiation (UVGI) treatment at single or successive doses of 60 mJ/cm2 after a short drying cycle (30 min, 70°C). The germicidal efficacy of this treatment was tested by spiking respirators with two staphylococcal bacteriophages (vB_HSa_2002 and P66 phages). The respirator performance was investigated by the following parameters: particle penetration (NaCl aerosol, 10-300 nm), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry and mechanical tensile tests. RESULTS: No viable phage particles were recovered from any of the respirators after decontamination (log reduction in virus titre >3), and no reduction in chemical or physical properties (SEM, particle penetrations <5%-6%) were observed. Increasing the UVGI dose 10-fold led to chemical alterations of the respirator filtration media (FTIR) but did not affect the physical properties (particle penetration), which was unaltered even at 3000 mJ/cm2 (50 cycles). When respirators had been used by healthcare workers and undergone decontamination, they had particle penetration significantly greater than never donned respirators. CONCLUSION: This decontamination procedure is an attractive method for respirators in case of shortages during a SARS pandemic. A successful implementation requires a careful design and particle penetration performance control tests over the successive reuse cycles.

From nano to micrometer size particles - A characterization of airborne cement particles during construction activities.

Although, photocatalytic cement contains nanosized TiO2, a possibly carcinogen, no exposure assessments exist for construction workers. We characterized airborne nanoparticle exposures during construction activities simulated in an exposure chamber. We collected some construction site samples for regular cement in Switzerland and Thailand for comparison. Airborne nanoparticles were characterized using scanning mobility particle sizer (SMPS), portable aerosol spectrometer (PAS), diffusion size classifier (DiSCmini), transmission electron microscopy (TEM), scanning electron microscope energy dispersive X-ray spectroscopy (SEM-EDX), and X-ray diffraction. Bagged photocatalytic cement had 2.0 wt% (GSD ± 0.55) TiO2, while TiO2 in aerosols reached 16.5 wt% (GSD ± 1.72) during bag emptying and 9.7 wt% (GSD ± 1.36) after sweeping. The airborne photocatalytic cement particles were far smaller (approximately 50 nm) compared to regular cement. Cutting blocks made from photocatalytic cement or concrete, resulted in similar amounts of airborne nano TiO2 (2.0 wt% GSD ± 0.57) particles as in bagged material. Both photocatalytic and regular cement had a geometric mean diameter (GMD) < 3.5 µm. Main exposures for Thai workers were during sweeping and Swiss workers during drilling and polishing cement blocks. Targeted nanoparticle exposure assessments are needed as a significantly greater exposure to nano TiO2 were observed than what would have been predicted from the material's nano- TiO2 contents.

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.

Physicochemical characterization of nebulized superparamagnetic iron oxide nanoparticles (SPIONs).

BACKGROUND: Aerosol-mediated delivery of nano-based therapeutics to the lung has emerged as a promising alternative for treatment and prevention of lung diseases. Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted significant attention for such applications due to their biocompatibility and magnetic properties. However, information is lacking about the characteristics of nebulized SPIONs for use as a therapeutic aerosol. To address this need, we conducted a physicochemical characterization of nebulized Rienso, a SPION-based formulation for intravenous treatment of anemia. METHODS: Four different concentrations of SPION suspensions were nebulized with a one-jet nebulizer. Particle size was measured in suspension by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and nanoparticle tracking analysis (NTA), and in the aerosol by a scanning mobility particle sizer (SMPS). RESULTS: The average particle size in suspension as measured by TEM, PCS, and NTA was 9±2 nm, 27±7 nm, and 56±10 nm, respectively. The particle size in suspension remained the same before and after the nebulization process. However, after aerosol collection in an impinger, the suspended particle size increased to 159±46 nm as measured by NTA. The aerosol particle concentration increased linearly with increasing suspension concentration, and the aerodynamic diameter remained relatively stable at around 75 nm as measured by SMPS. CONCLUSIONS: We demonstrated that the total number and particle size in the aerosol were modulated as a function of the initial concentration in the nebulizer. The data obtained mark the first known independent characterization of nebulized Rienso and, as such, provide critical information on the behavior of Rienso nanoparticles in an aerosol. The data obtained in this study add new knowledge to the existing body of literature on potential applications of SPION suspensions as inhaled aerosol therapeutics.