The role of puff volume in vaping emissions, inhalation risks, and metabolic perturbations: a pilot study.

Secondhand vaping exposure is an emerging public health concern that remains understudied. In this study, saliva and exhaled emissions from ENDS users (secondhand) and non-ENDS users (baseline) were collected, firsthand emissions were generated using an automated ENDS aerosol generation system programmed to simulate puffing topography profiles collected from ENDS users. Particulate concentrations and sizes along with volatile organic compounds were characterized. We revealed puffing topography metrics as potential mediators of firsthand and secondhand particle and chemical exposures, as well as metabolic and respiratory health outcomes. Particle deposition modeling revealed that while secondhand emissions displayed smaller deposited mass, total and pulmonary particle deposition fractions were higher than firsthand deposition levels, possibly due to smaller secondhand emission particle diameters. Lastly, untargeted metabolomic profiling of salivary biomarkers of lung injury due to firsthand ENDS exposures revealed potential early indicators of respiratory distress that may also be relevant in bystanders exposed to secondhand vaping scenarios. By leveraging system toxicology, we identified 10 metabolites, including leukotriene D4, that could potentially serve as biomarkers for ENDS use, exposure estimation, and the prediction of vaping-related disease. This study highlights characterization of vaping behavior is an important exposure component in advancing our understanding of potential health effects in ENDS users and bystanders.

Investigation of pulmonary inflammatory responses following intratracheal instillation of and inhalation exposure to polypropylene microplastics.

BACKGROUND: Microplastics have been detected in the atmosphere as well as in the ocean, and there is concern about their biological effects in the lungs. We conducted a short-term inhalation exposure and intratracheal instillation using rats to evaluate lung disorders related to microplastics. We conducted an inhalation exposure of polypropylene fine powder at a low concentration of 2 mg/m3 and a high concentration of 10 mg/m3 on 8-week-old male Fischer 344 rats for 6 h a day, 5 days a week for 4 weeks. We also conducted an intratracheal instillation of polypropylene at a low dose of 0.2 mg/rat and a high dose of 1.0 mg/rat on 12-week-old male Fischer 344 rats. Rats were dissected from 3 days to 6 months after both exposures, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected to analyze lung inflammation and lung injury. RESULTS: Both exposures to polypropylene induced a persistent influx of inflammatory cells and expression of CINC-1, CINC-2, and MPO in BALF from 1 month after exposure. Genetic analysis showed a significant increase in inflammation-related factors for up to 6 months. The low concentration in the inhalation exposure of polypropylene also induced mild lung inflammation. CONCLUSION: These findings suggest that inhaled polypropylene, which is a microplastic, induces persistent lung inflammation and has the potential for lung disorder. Exposure to 2 mg/m3 induced inflammatory changes and was thought to be the Lowest Observed Adverse Effect Level (LOAEL) for acute effects of polypropylene. However, considering the concentration of microplastics in a real general environment, the risk of environmental hazards to humans may be low.

Lung carcinogenicity by whole body inhalation exposure to Anatase-type Nano-titanium Dioxide in rats.

To investigate the carcinogenicity of anatase-type nano-titanium dioxide (aNTiO2), F344/DuCrlCrlj rats were exposed to aNTiO2 aerosol at concentrations of 0, 0.5, 2, and 8 mg/m3. The rats were divided into 2 groups: carcinogenicity study groups were exposed for two years, and satellite study groups were exposed for one year followed by recovery for 1 day, 26 weeks, and 52 weeks after the end of exposure. In the carcinogenicity groups, bronchiolo-alveolar carcinomas were observed in two 8 mg/m3-exposed males, showing an increasing trend by Peto's test. However, this incidence was at the upper limit of JBRC's historical control data. Bronchiolo-alveolar adenomas were observed in 1, 2, 3, and 4 rats of the 0, 0.5, 2, and 8 mg/m3-exposed females and were not statistically significant. However, the incidence in the 8 mg/m3-exposed females exceeded JBRC's historical control data. Therefore, we conclude there is equivocal evidence for the carcinogenicity of aNTiO2 in rats. No lung tumors were observed in the satellite groups. Particle-induced non-neoplastic lesions (alveolar epithelial hyperplasia and focal fibrosis) were observed in exposed males and females in both the carcinogenicity and satellite groups. Increased lung weight and neutrophils of bronchoalveolar lavage fluid were observed in the 8 mg/m3-exposed carcinogenicity groups. The aNTiO2 deposited in the lungs of the satellite group rats was decreased at 26 weeks after the end of exposure compared to 1 day after the end of exposure. At 52 weeks after the end of exposure, the decreased level was the same at 26 weeks after the end of exposure.

Depleted Housing Elicits Cardiopulmonary Dysfunction After a Single Flaming Eucalyptus Wildfire Smoke Exposure in a Sex-Specific Manner in ApoE Knockout Mice.

Although it is well established that wildfire smoke exposure can increase cardiovascular morbidity and mortality, the combined effects of non-chemical stressors and wildfire smoke remains understudied. Housing is a non-chemical stressor that is a major determinant of cardiovascular health, however, disparities in neighborhood and social status have exacerbated the cardiovascular health gaps within the United States. Further, pre-existing cardiovascular morbidities, such as atherosclerosis, can worsen the response to wildfire smoke exposures. This represents a potentially hazardous interaction between inadequate housing and stress, cardiovascular morbidities, and worsened responses to wildfire smoke exposures. The purpose of this study was to examine the effects of enriched (EH) versus depleted (DH) housing on pulmonary and cardiovascular responses to a single flaming eucalyptus wildfire smoke (WS) exposure in male and female apolipoprotein E (ApoE) knockout mice, which develop an atherosclerosis-like phenotype. The results of this study show that cardiopulmonary responses to WS exposure occur in a sex-specific manner. EH blunts adverse WS-induced ventilatory responses, specifically an increase in tidal volume (TV), expiratory time (Te), and relaxation time (RT) after a WS exposure, but only in females. EH also blunted an increase in isovolumic relaxation time (IVRT) and the myocardial performance index (MPI) 1-week after exposures, also only in females. Our results suggest that housing alters the cardiovascular response to a single WS exposure, and that DH might cause increased susceptibility to environmental exposures that manifest in altered ventilation patterns and diastolic dysfunction in a sex-specific manner.

Impact of Respiratory Dust on Health: A Comparison Based on the Toxicity of PM2.5, Silica, and Nanosilica.

Respiratory dust of different particle sizes in the environment causes diverse health effects when entering the human body and makes acute or chronic damage through multiple systems and organs. However, the precise toxic effects and potential mechanisms induced by dust of different particle sizes have not been systematically summarized. In this study, we described the sources and characteristics of three different particle sizes of dust: PM2.5 (<2.5 µm), silica (<5 µm), and nanosilica (<100 nm). Based on their respective characteristics, we further explored the main toxicity induced by silica, PM2.5, and nanosilica in vivo and in vitro. Furthermore, we evaluated the health implications of respiratory dust on the human body, and especially proposed potential synergistic effects, considering current studies. In summary, this review summarized the health hazards and toxic mechanisms associated with respiratory dust of different particle sizes. It could provide new insights for investigating the synergistic effects of co-exposure to respiratory dust of different particle sizes in mixed environments.

The oxidative stress-dependent pulmonary inflammation of inhalable multi-walled carbon nanotube-containing nano-concrete dust and its comparison with conventional concrete dust and DQ12.

Nano-concrete, which is an admixture of nanomaterials in concrete recipes, has been investigated to overcome the limitations of existing concrete, such as its stability and strength. However, there is no information on the human health effects of broken-down dust released during the construction and demolition efforts. In this study, we prepared an inhalable fraction of multi-walled carbon nanotube-containing nano-concrete dust and performed comparative toxicity studies with conventional concrete dust and DQ12 using a rat intratracheal instillation model. Although the recipes for concrete and nano-concrete are entirely different, the pulverized dust samples showed similar physicochemical properties, such as 0.46-0.48 µm diameter and chemical composition. Both concrete and nano-concrete dust exhibited similar patterns and magnitudes, representing acute neutrophilic inflammation and chronic active inflammation with lymphocyte infiltration. The toxicity endpoints of the tested particles at both time points showed an excellent correlation with the reactive oxygen species levels released from the alveolar macrophages, highlighting that alveolar macrophages are the primary target cells and that the oxidative stress paradigm is the main toxicity mechanism of the tested particles. In addition, the toxicity potentials of both concrete and nano-concrete dust were more than 10 times lower than that of DQ12.

Occupational exposure to welding fume in Australia: An online survey.

OBJECTIVE: This survey aimed to investigate exposure to welding fume in Australian workplaces and the use of protective and control measures among workers. METHODS: Data were collected via a cross-sectional online survey of workers and employers involved in welding in Australia. Survey questions focused on the determinants of exposure to welding fume, welding experience and qualifications, and use of control measures. RESULTS: There were 634 respondents to the survey across Australia of whom 577 (91%) were assessed as being exposed to welding fume, most at high levels. Welders undertook a wide range of types of welding, and higher-risk welding such as in confined and restricted spaces was common. Most workplaces did not have any form of mechanical ventilation, and use of air-supplied respiratory protection was poor even when ventilation was not used. CONCLUSION: Welders in Australia are exposed to several carcinogens, particularly welding fume, hexavalent chromium (CrVI) and nickel, and the use of control measures is sub-optimal. IMPLICATIONS FOR PUBLIC HEALTH: Higher-order controls are the best way to reduce exposure to carcinogens in the workplace. The lack of use of these controls by Australian welders is concerning and needs to be a focus of attention by regulators and companies.

Toxicity and biokinetics following pulmonary exposure to aluminium (aluminum): A review.

During the manufacture and use of aluminium (aluminum), inhalation exposure may occur. We reviewed the pulmonary toxicity of this metal including its toxicokinetics. The normal serum/plasma level based on 17 studies was 5.7 ± 7.7 µg Al/L (mean ± SD). The normal urine level based on 15 studies was 7.7 ± 5.3 µg/L. Bodily fluid and tissue levels during occupational exposure are also provided, and the urine level was increased in aluminium welders (43 ± 33 µg/L) based on 7 studies. Some studies demonstrated that aluminium from occupational exposure can remain in the body for years. Excretion pathways include urine and faeces. Toxicity studies were mostly on aluminium flakes, aluminium oxide and aluminium chlorohydrate as well as on mixed exposure, e.g. in aluminium smelters. Endpoints affected by pulmonary aluminium exposure include body weight, lung function, lung fibrosis, pulmonary inflammation and neurotoxicity. In men exposed to aluminium oxide particles (3.2 µm) for two hours, lowest observed adverse effect concentration (LOAEC) was 4 mg Al2O3/m3 (= 2.1 mg Al/m3), based on increased neutrophils in sputum. With the note that a similar but not statistically significant increase was seen during control exposure. In animal studies LOAECs start at 0.3 mg Al/m3. In intratracheal instillation studies, all done with aluminium oxide and mainly nanomaterials, lowest observed adverse effect levels (LOAELs) started at 1.3 mg Al/kg body weight (bw) (except one study with a LOAEL of ∼0.1 mg Al/kg bw). The collected data provide information regarding hazard identification and characterisation of pulmonary exposure to aluminium.

Impact of climate change on paediatric respiratory health: pollutants and aeroallergens.

Paediatric populations are particularly vulnerable to respiratory diseases caused and exacerbated by aeroallergens, pollutants and infectious agents. Worsening climate change is expected to increase the prevalence of pollutants and aeroallergens while amplifying disease severity and causing disproportionate effects in under-resourced areas. The purpose of this narrative review is to summarise the role of anthropogenic climate change in the literature examining the future impact of aeroallergens, pollutants and infectious agents on paediatric respiratory diseases with a focus on equitable disease mitigation. The aeroallergens selected for discussion include pollen, dust mites and mould as these are prevalent triggers of paediatric asthma worldwide. Human rhinovirus and respiratory syncytial virus are key viruses interacting with climate change and pollution and are primary causal agents of viral respiratory disease. Within this review, we present the propensity for aeroallergens, climate change and pollution to synergistically exacerbate paediatric respiratory disease and outline measures that can ameliorate the expected increase in morbidity and severity of disease through a health equity lens. We support shifting from fossil fuels to renewable energy worldwide, across sectors, as a primary means of reducing increases in morbidity.

Microplastic and plastic pollution: impact on respiratory disease and health.

Throughout their lifecycle, from production to use and upon disposal, plastics release chemicals and particles known as micro- and nanoplastics (MNPs) that can accumulate in the environment. MNPs have been detected in different locations of the human body, including in our lungs. This is likely a consequence of MNP exposure through the air we breathe. Yet, we still lack a comprehensive understanding of the impact that MNP exposure may have on respiratory disease and health. In this review, we have collated the current body of evidence on the implications of MNP inhalation on human lung health from in vitro, in vivo and occupational exposure studies. We focused on interactions between MNP pollution and different specific lung-resident cells and respiratory diseases. We conclude that it is evident that MNPs possess the capacity to affect lung tissue in disease and health. Yet, it remains unclear to which extent this occurs upon exposure to ambient levels of MNPs, emphasising the need for a more comprehensive evaluation of environmental MNP exposure levels in everyday life.

Characterization of Mild Delayed Gestational Hypertension in Rats Following Ozone Exposure.

The contribution of air pollution-induced cardiopulmonary damage on the development of hypertensive disorders of pregnancy and other adverse outcomes of pregnancy has gained increased attention as epidemiological data continue to highlight spatiotemporal pregnancy trends related to air pollution exposure. However clinical mechanistic data surrounding gestational complications remain sparse, necessitating the need for the use of animal models to study these types of complications of pregnancy. The current study seeks to examine the real-time effects of mid-gestational ozone exposure on maternal blood pressure and body temperature through the use of radiotelemetry in a rat model. The exposure resulted in acute depression of heart rate and core body temperature as compared to control animals. Ozone-exposed animals also presented with a slight but significant increase in arterial blood pressure which was perpetuated until term. The data presented here illustrates the feasibility of murine models to assess cardiovascular complications caused by inhaled toxicants during the window of pregnancy.

Transcriptome changes in humans acutely exposed to nanoparticles during grinding of dental nanocomposites.

Aim: Today, there is a lack of research studies concerning human acute exposure to nanoparticles (NPs). Our investigation aimed to simulate real-world acute inhalation exposure to NPs released during work with dental nanocomposites in a dental office or technician laboratory. Methods: Blood samples from female volunteers were processed before and after inhalation exposure. Transcriptomic mRNA and miRNA expression changes were analyzed. Results: We detected large interindividual variability, 90 significantly deregulated mRNAs, and 4 miRNAs when samples of participants before and after dental nanocomposite grinding were compared. Conclusion: The results suggest that inhaled dental NPs may present an occupational hazard to human health, as indicated by the changes in the processes related to oxidative stress, synthesis of eicosanoids, and cell division.

What is this article about? We searched for a possible impact of acute inhalation exposure to nanoparticles (NPs) released during the grinding of dental nanocomposites used for teeth reconstruction. The exposure design utilized in our study simulated the acute exposure of the dental staff to the NPs. Our research fills the gaps in knowledge in the field of acute human inhalation exposure to dental nanocomposites.What were the results? Results indicate that the impact of exposure to NPs is dependent on the style of working as well as on the interindividual biological variability among study subjects. Changes in expression levels of genes associated with an increase of oxidative stress, synthesis of eicosanoids (signaling molecules related to e.g., immune responses), and cell division were detected.What do the results of the study mean? All the observed changes may contribute to the pathogenesis of neurodegenerative disorders, carcinogenesis, or problems during pregnancy. Occupational exposure to inhaled NPs, including those generated in dental practice can pose a significant health risk, and protective measures when working with these materials should be considered. More research is needed to compare our results with chronic (long-term) exposure to similar materials to show the hazards related to their inhalation.

PM10-bound microplastics and trace metals: A public health insight from the Korean subway and indoor environments.

Inhalable airborne microplastics (MPs) presented in indoor and outdoor environments, can deeply penetrate the lungs, potentially triggering inflammation and respiratory illnesses. The present study aims to evaluate human health risks from respirable particulate matter (PM)-bound trace metals and MPs in indoor (SW- subway and IRH- indoor residential houses) and outdoor (OD) environments. This research provides an initial approach to human respiratory tract (HRT) mass depositions of PM10-bound total MPs and nine specific MP types to predict potential human health threats from inhalation exposure. Results indicate that PM-bound trace metals and MPs were around 4 times higher in SW microenvironments compared to OD locations. In IRH, cancer risk (CR) levels were estimated 9 and 4 times higher for PM10 and PM2.5, respectively. Additionally, MP particle depositions per gram of lung cell weight were highest in IRH (23.77), followed by OD and SW. Whereas, lifetime alveoli depositions of MPs were estimated at 13.73 MP/g, which exceeds previously reported respiratory disease fatality cases by 10 to 5 times. Prolonged exposure duration at IRH emerged as a key factor contributing to increased CR and MP lung deposition levels. This research highlights severe lung risks from inhaling PM-bound MPs and metals, offering valuable health insights.

Risk assessment for perfluorooctanoic acid (PFOA) in air, blood serum and water: mortality from liver and kidney disease.

BACKGROUND: Cancer and non-cancer associations have been observed with PFAS (perfluoroalkyl and polyfluoroalkyl) substances in the general population, in populations from locally contaminated environments and in exposed workers. METHODS: A quantitative risk assessment on the PFAS substance perfluorooctanoic acid (PFOA) was conducted for six outcomes using two occupational mortality studies that reported sufficient data to estimate exposure-relationships in relation to serum PFOA levels. Excess lifetime mortality risks were calculated using a life table procedure that applies an exposure response to time-dependent PFOA serum levels for a surviving hypothetical population from ages 20 to 85. Both occupational and general population exposures were described as serum levels, and as air and drinking water concentrations. RESULTS: The estimated occupational inhalation concentrations conferring the benchmark one-per-thousand lifetime risk were 0.21 µg/m3 for chronic kidney disease, 1.0 µg/m3 for kidney cancer and (from the two studies) 0.67 and 1.97 µg/m3 for chronic liver disease. Specific excess lifetime risks estimated in the general population at current PFOA serum levels (~ 1 ng/mL) range 1.5-32 per 100 000 which corresponds to drinking water concentrations of less than 10 ppt. CONCLUSION: Over eight outcome risk estimates, the serum PFOA concentrations conferring 1/1000 occupational lifetime risk ranged 44 to 416 ng/mL corresponding to air concentrations ranging 0.21 to 1.99 µg/m3. The analyses provide a preliminary PFOA quantitative risk assessment for liver and kidney disease mortality which, together with reported assessments for several other end-points, would inform policy on PFAS.

Tralopyril poisoning due to respiratory exposure.

INTRODUCTION: Tralopyril is a metabolite of the pesticide chlorfenapyr. Direct toxicity by tralopyril has not been described. We report two cases of tralopyril poisoning via inhalation. CASE PRESENTATIONS: Two workers developed heat intolerance, diaphoresis, and weight loss after occupational inhalational exposure to tralopyril. Patient 1: The exposure was due to the absence of respiratory protection. Magnetic resonance imaging showed abnormal signals in the bilateral periventricular white matter, corpus callosum, basal ganglia, brainstem, and spinal cord. The patient's blood tralopyril concentrations on days 1, 3, 5, 8, and 11 post-admission were 1.09 mg/L, 1.04 mg/L, 1.01 mg/L, 0.71 mg/L, and 0.313 mg/L, respectively. Haemoperfusion (HA330), haemoperfusion (HA380), and haemodiafiltration were performed on days 1-3, 5-8, and 9-10, respectively. Patient 2: The patient's symptoms followed inappropriate use of respiratory protection. His blood tralopyril concentrations on days 1, 4, 5, and 6 were 0.592 mg/L, 0.482 mg/L, 0.370 mg/L, and 0.228 mg/L, respectively. DISCUSSION: The patients presented with features typical of chlorfenapyr poisoning, which suggests that tralopyril is the main toxic metabolite of chlorfenapyr. CONCLUSION: Tralopyril can be absorbed by inhalation, leading to delayed clinical symptoms and organ damage, including toxic encephalopathy and spinal cord damage.

3D printer emissions elicit filament-specific and dose-dependent metabolic and genotoxic effects in human airway epithelial cells.

Three-dimensional (3D) printers have become popular educational tools in secondary and post-secondary STEM curriculum; however, concerns have emerged regarding inhalation exposures and associated health risks. Current evidence suggests that filament materials and site conditions may cause differences in the chemical profiles and toxicological properties of 3D printer emissions; however, few studies have evaluated exposures directly in the classroom. In this study, we monitored and sampled particulate matter (PM) emitted from acrylonitrile-butadiene-styrene (ABS) and polylactic acid (PLA) filaments during a 3-hour 3D printing session in a high school classroom using aerosol monitoring instrumentation and collection media. To evaluate potential inhalation risks, Multiple Path Particle Dosimetry (MPPD) modeling was used to estimate inhaled doses and calculate in vitro concentrations based on the observed aerosol data and specific lung and breathing characteristics. Dynamic light scattering was used to evaluate the hydrodynamic diameter, zeta potential, and polydispersity index (PDI) of extracted PM emissions dispersed in cell culture media. Small airway epithelial cells (SAEC) were employed to determine cellular viability, genotoxic, inflammatory, and metabolic responses to each emission exposure using MTS, ELISA, and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. Aerosol monitoring data revealed that emissions from ABS and PLA filaments generated similar PM concentrations within the ultrafine and fine ranges. However, DLS analysis showed differences in the physicochemical properties of ABS and PLA PM, where the hydrodynamic diameter of PLA PM was greater than ABS PM, which may have influenced particle deposition rates and cellular outcomes. While exposure to both ABS and PLA PM reduced cell viability and induced MDM2, an indicator of genomic instability, PLA PM alone increased gamma-H2AX, a marker of double-stranded DNA breaks. ABS and PLA emissions also increased the release of pro-inflammatory cytokines, although this did not reach significance. Furthermore, metabolic profiling via high performance liquid chromatography-mass spectrometry (HPLC-MS) and subsequent pathway analysis revealed filament and dose dependent cellular metabolic alterations. Notably, our metabolomic analysis also revealed key metabolites and pathways implicated in PM-induced oxidative stress, DNA damage, and respiratory disease that were perturbed across both tested doses for a given filament. Taken together, these findings suggest that use of ABS and PLA filaments in 3D printers within school settings may potentially contribute to adverse respiratory responses especially in vulnerable populations.

Exposure to tungsten particles via inhalation triggers early toxicity marker expression in the rat brain.

OBJECTIVE: Our work is focused on tungsten, considered as an emerging contaminant. Its environmental dispersion is partly due to mining and military activities. Exposure scenario can also be occupational, in areas such as the hard metal industry and specific nuclear facilities. Our study investigated the cerebral effects induced by the inhalation of tungsten particles. METHODS: Inhalation exposure campaigns were carried out at two different concentrations (5 and 80 mg/m3) in single and repeated modes (4 consecutive days) in adult rats within a nose-only inhalation chamber. Processes involved in brain toxicity were investigated 24 h after exposure. RESULTS AND DISCUSSION: Site-specific effects in terms of neuroanatomy and concentration-dependent changes in specific cellular actors were observed. Results obtained in the olfactory bulb suggest a potential early effect on the survival of microglial cells. Depending on the mode of exposure, these cells showed a decrease in density accompanied by an increase in an apoptotic marker. An abnormal phenotype of the nuclei of mature neurons, suggesting neuronal suffering, was also observed in the frontal cortex, and can be linked to the involvement of oxidative stress. The differential effects observed according to exposure patterns could involve two components: local (brain-specific) and/or systemic. Indeed, tungsten, in addition to being found in the lungs and kidneys, was present in the brain of animals exposed to the high concentration. CONCLUSION: Our data question the perceived innocuity of tungsten relative to other metals and raise hypotheses regarding possible adaptive or neurotoxic mechanisms that could ultimately alter neuronal integrity.

Worse pulmonary function in association with cumulative exposure to nanomaterials. Hints of a mediation effect via pulmonary inflammation.

BACKGROUND: Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project. RESULTS: Our findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV1 and FEF25 - 75%, which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1ß and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV1/FVC ratio. This pattern was not observed for other pulmonary function parameters. CONCLUSIONS: Safeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time.

Controlled human exposures to diesel exhaust or particle-depleted diesel exhaust with allergen modulates transcriptomic responses in the lung.

The evidence associating traffic-related air pollution (TRAP) with allergic asthma is growing, but the underlying mechanisms for this association remain unclear. The airway epithelium is the primary tissue exposed to TRAP, hence understanding its interactions with TRAP and allergen is important. Diesel exhaust (DE), a paradigm of TRAP, consists of particulate matter (PM) and gases. Modern diesel engines often have catalytic diesel particulate filters to reduce PM output, but these may increase gaseous concentrations, and their benefits on human health cannot be assumed. We conducted a randomized, double-blinded, crossover study using our unique in vivo human exposure system to investigate the effects of DE and allergen co-exposure, with or without particle depletion as a proxy for catalytic diesel particulate filters, on the airway epithelial transcriptome. Participants were exposed for 2 h before an allergen inhalation challenge, with each receiving filtered air and saline (FA-S), filtered air and allergen (FA-A), DE and allergen (DE-A), or particle-depleted DE and allergen (PDDE-A), over four different occasions, each separated by a 4-week washout period. Endobronchial brushings were collected 48 h after each exposure, and total RNA was sequenced. Differentially expressed genes (DEGs) were identified using DESeq2, followed by GO enrichment and pathway analysis. FA-A, DE-A, and PDDE-A exposures significantly modulated genes relative to FA-S, with 462 unique DEGs identified. FA-A uniquely modulated the highest number (↑178, ↓155), followed by DE-A (↑44, ↓23), and then PDDE-A exposure (↑15, ↓2); 6 DEGs (↑4, ↓2) were modulated by all three conditions. Exposure to PDDE-A resulted in modulation of 285 DEGs compared to DE-A exposure, further revealing 26 biological process GO terms, including "cellular response to chemokine" and "inflammatory response". The transcriptional epithelial response to diesel exhaust and allergen co-exposure is enriched in inflammatory mediators, the pattern of which is altered upon particle depletion.