How can we reduce biomedical research's carbon footprint?

Biomedical research is a significant contributor to the global carbon footprint. Practices are available that could make a difference; however, there are significant obstacles ahead, including a lack of specialist expertise in sustainable research practices.

Multiomic Signatures of Traffic-Related Air Pollution in London Reveal Potential Short-Term Perturbations in Gut Microbiome-Related Pathways.

This randomized crossover study investigated the metabolic and mRNA alterations associated with exposure to high and low traffic-related air pollution (TRAP) in 50 participants who were either healthy or were diagnosed with chronic pulmonary obstructive disease (COPD) or ischemic heart disease (IHD). For the first time, this study combined transcriptomics and serum metabolomics measured in the same participants over multiple time points (2 h before, and 2 and 24 h after exposure) and over two contrasted exposure regimes to identify potential multiomic modifications linked to TRAP exposure. With a multivariate normal model, we identified 78 metabolic features and 53 mRNA features associated with at least one TRAP exposure. Nitrogen dioxide (NO2) emerged as the dominant pollutant, with 67 unique associated metabolomic features. Pathway analysis and annotation of metabolic features consistently indicated perturbations in the tryptophan metabolism associated with NO2 exposure, particularly in the gut-microbiome-associated indole pathway. Conditional multiomics networks revealed complex and intricate mechanisms associated with TRAP exposure, with some effects persisting 24 h after exposure. Our findings indicate that exposure to TRAP can alter important physiological mechanisms even after a short-term exposure of a 2 h walk. We describe for the first time a potential link between NO2 exposure and perturbation of the microbiome-related pathways.

Long-term ambient ozone, omega-3 fatty acid, genetic susceptibility, and risk of mental disorders among middle-aged and older adults in UK biobank.

BACKGROUND: Evidence linking ozone to depression and anxiety disorders remains sparse and results are heterogeneous. It remains unknown whether omega-3 fatty acid, or genetic susceptibility of mental disorders modify the impacts of ozone. The aim is to assess the associations of ambient ozone with depression and anxiety, and further explore the potential modification effects of omega-3 fatty acid and genetic susceptibility. METHODS: In total of 257,534 participants were enrolled from 2006 to 2010 and followed up to 2016. Depression and anxiety were assessed using mental health questionnaires, primary care records and hospital admission records. The annual average concentrations of ozone were calculated and linked to individuals by home address. Dietary intake and plasma concentration were selected to reflect levels of omega-3 fatty acid. Polygenetic risk scores were selected to reflect genetic susceptibility. We examined the associations of ozone and incident mental disorders, and potential modification of omega-3 fatty acid and genetic susceptibility. RESULTS: Incidences of depression (N = 6957) and anxiety (N = 6944) was associated with increase of ozone. Higher levels of omega-3 fatty acid might attenuate the ozone related depression risk. However, the modification effects of genetic susceptibility were not found. CONCLUSIONS: Long-term exposure to ambient ozone increase the risk of mental disorders among the middle aged and older adults, and omega-3 fatty acid could reduce the adverse effects of ozone on mental health. Higher intake of omega-3 fatty acid is a potential strategy to prevent the risks caused by ozone on public mental health.

Could the association between ozone and arterial stiffness be modified by fish oil supplementation?

BACKGROUND: Arterial stiffness (AS) is an important predicting factor for cardiovascular disease. However, no epidemiological studies have ever explored the mediating role of biomarkers in the association between ozone and AS, nor weather fish oil modified such association. METHODS: Study participants were drawn from the UK biobank, and a total of 95,699 middle-aged and older adults were included in this study. Ozone was obtained from Community Multiscale Air Quality (CMAQ) model matched to residential addresses, fish oil from self-reported intake, and arterial stiffness was based on device measurements. First, we applied a double robust approach to explore the association between ozone or fish oil intake and arterial stiffness, adjusting for potential confounders at the individual and regional levels. Then, how triglycerides, apolipoprotein B (Apo B)/apolipoprotein A (ApoA) and non-high-density lipoprotein cholesterol (Non-HDL-C) mediate the relationship between ozone and AS. Last, the modifying role of fish oil was further explored by stratified analysis. RESULTS: The mean age of participants was 55 years; annual average ozone exposure was associated with ASI (beta:0.189 [95%CI: 0.146 to 0.233], P < 0.001), and compared to participants who did not consume fish oil, fish oil users had a lower ASI (beta: 0.061 [95%CI: -0.111 to -0.010], P = 0.016). The relationship between ozone exposure and AS was mediated by triglycerides, ApoB/ApoA, and Non-HDL-C with mediation proportions ranging from 10.90% to 18.30%. Stratified analysis showed lower estimates on the ozone-AS relationship in fish oil users (P = 0.011). CONCLUSION: Ozone exposure was associated with higher levels of arterial stiffness, in contrast to fish oil consumption, which showed a protective association. The association between ozone exposure and arterial stiffness was partially mediated by some biomarkers. In the general population, fish oil consumption might provide protection against ozone-related AS.

Cross-sectional study of household solid fuel use and renal function in older adults in China.

BACKGROUND: Emerging evidence links outdoor air pollution and declined renal function but the relationship between household air pollution and renal function is not well understood. METHODS: Using cross-sectional data from the multi-provincial INTERMAP-China Prospective Study, we collected blood samples and questionnaire information on stove use and socio-demographic factors. We calculated estimated glomerular filtration rate (eGFR) from serum creatinine to assess renal function. Participants with eGFR <60 mL/min per 1.73 m2 were defined as having chronic kidney disease (CKD) in this analysis. Generalized estimating equations were used to estimate the association of household fuel with renal function and prevalent CKD in models adjusting for confounders. RESULTS: Among the 646 enrolled adults (40-79y; 56% female), one-third exclusively used clean fuel (gas and electric) cookstoves and 11% of northern China participants (n = 49 of 434) used only clean fuel heaters, whereas the rest used solid fuel. In multivariable models, use of solid fuel cookstoves was associated with 0.17 ml/min/1.73 m2 (95% CI: -0.30, 0.64) higher eGFR and 19% (0.86, 1.64) higher prevalence of CKD than exclusive clean fuel use. Greater intensity of solid fuel use was associated with 0.25 ml/min/1.73 m2 (-0.71, 0.21) lower eGFR per 5 stove-use years, though the confidence intervals included the null, while greater current intensity of indoor solid fuel use was associated with 1.02 (1.00, 1.04) higher prevalent CKD per 100 stove-use days per year. Larger associations between current solid fuel use and intensity of use with lower eGFR and prevalent CKD were observed among participants in southern China, those with hypertension or diabetes (eGFR only), and females (CKD only), through these groups had small sample sizes and some confidence intervals included the null. CONCLUSION: We found inconsistent evidence associating household solid fuel use and renal function in this cross-sectional study of peri-urban Chinese adults.

Investigating the impact of London's ultra low emission zone on children's health: children's health in London and Luton (CHILL) protocol for a prospective parallel cohort study.

BACKGROUND: Air pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are urgently needed both to improve public health now, and prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver health benefits is lacking. We describe a natural experiment study (CHILL: Children's Health in London and Luton) to evaluate the impacts of the introduction of London's Ultra Low Emission Zone (ULEZ) on children's health. METHODS: CHILL is a prospective two-arm parallel longitudinal cohort study recruiting children at age 6-9 years from primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site), with the primary outcome being the impact of changes in annual air pollutant exposures (nitrogen oxides [NOx], nitrogen dioxide [NO2], particulate matter with a diameter of less than 2.5micrograms [PM2.5], and less than 10 micrograms [PM10]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV1) over five years. Secondary outcomes include physical activity, cognitive development, mental health, quality of life, health inequalities, and a range of respiratory and health economic data. DISCUSSION: CHILL's prospective parallel cohort design will enable robust conclusions to be drawn on the effectiveness of the ULEZ at improving air quality and delivering improvements in children's respiratory health. With increasing proportions of the world's population now living in large urban areas exceeding World Health Organisation air pollution limit guidelines, our study findings will have important implications for the design and implementation of Low Emission and Clean Air Zones in the UK, and worldwide. CLINICALTRIALS: GOV: NCT04695093 (05/01/2021).

Exposure to Elevated Nitrogen Dioxide Concentrations and Cardiac Remodeling in Patients With Dilated Cardiomyopathy.

BACKGROUND: Empirical evidence suggests a strong link between exposure to air pollution and heart failure incidence, hospitalizations, and mortality, but the biological basis of this remains unclear. We sought to determine the relationship between differential air pollution levels and changes in cardiac structure and function in patients with dilated cardiomyopathy. METHODS AND RESULTS: We undertook a prospective longitudinal observational cohort study of patients in England with dilated cardiomyopathy (enrollment 2009-2015, n = 716, 66% male, 85% Caucasian) and conducted cross sectional analysis at the time of study enrollment. Annual average air pollution exposure estimates for nitrogen dioxide (NO2) and particulate matter with diameter of 2.5 µm or less (PM2.5) at enrolment were assigned to each residential postcode (on average 12 households). The relationship between air pollution and cardiac morphology was assessed using linear regression modelling. Greater ambient exposure to NO2 was associated with higher indexed left ventricular (LV) mass (4.3 g/m2 increase per interquartile range increase in NO2, 95% confidence interval 1.9-7.0 g/m2) and lower LV ejection fraction (-1.5% decrease per interquartile range increase in NO2, 95% confidence interval -2.7% to -0.2%), independent of age, sex, socioeconomic status, and clinical covariates. The associations were robust to adjustment for smoking status and geographical clustering by postcode area. The effect of air pollution on LV mass was greatest in women. These effects were specific to NO2 exposure. CONCLUSIONS: Exposure to air pollution is associated with raised LV mass and lower LV ejection fraction, with the strongest effect in women. Although epidemiological associations between air pollution and heart failure have been established and supported by preclinical studies, our findings provide novel empirical evidence of cardiac remodeling and exposure to air pollution with important clinical and public health implications.

A Review of Road Traffic-Derived Non-Exhaust Particles: Emissions, Physicochemical Characteristics, Health Risks, and Mitigation Measures.

Implementation of regulatory standards has reduced exhaust emissions of particulate matter from road traffic substantially in the developed world. However, nonexhaust particle emissions arising from the wear of brakes, tires, and the road surface, together with the resuspension of road dust, are unregulated and exceed exhaust emissions in many jurisdictions. While knowledge of the sources of nonexhaust particles is fairly good, source-specific measurements of airborne concentrations are few, and studies of the toxicology and epidemiology do not give a clear picture of the health risk posed. This paper reviews the current state of knowledge, with a strong focus on health-related research, highlighting areas where further research is an essential prerequisite for developing focused policy responses to nonexhaust particles.

Automated classification of time-activity-location patterns for improved estimation of personal exposure to air pollution.

BACKGROUND: Air pollution epidemiology has primarily relied on measurements from fixed outdoor air quality monitoring stations to derive population-scale exposure. Characterisation of individual time-activity-location patterns is critical for accurate estimations of personal exposure and dose because pollutant concentrations and inhalation rates vary significantly by location and activity. METHODS: We developed and evaluated an automated model to classify major exposure-related microenvironments (home, work, other static, in-transit) and separated them into indoor and outdoor locations, sleeping activity and five modes of transport (walking, cycling, car, bus, metro/train) with multidisciplinary methods from the fields of movement ecology and artificial intelligence. As input parameters, we used GPS coordinates, accelerometry, and noise, collected at 1 min intervals with a validated Personal Air quality Monitor (PAM) carried by 35 volunteers for one week each. The model classifications were then evaluated against manual time-activity logs kept by participants. RESULTS: Overall, the model performed reliably in classifying home, work, and other indoor microenvironments (F1-score>0.70) but only moderately well for sleeping and visits to outdoor microenvironments (F1-score=0.57 and 0.3 respectively). Random forest approaches performed very well in classifying modes of transport (F1-score>0.91). We found that the performance of the automated methods significantly surpassed those of manual logs. CONCLUSIONS: Automated models for time-activity classification can markedly improve exposure metrics. Such models can be developed in many programming languages, and if well formulated can have general applicability in large-scale health studies, providing a comprehensive picture of environmental health risks during daily life with readily gathered parameters from smartphone technologies.

Personal exposure to air pollution and respiratory health of COPD patients in London.

Previous studies have investigated the effects of air pollution on chronic obstructive pulmonary disease (COPD) patients using either fixed-site measurements or a limited number of personal measurements, usually for one pollutant and a short time period. These limitations may introduce bias and distort the epidemiological associations as they do not account for all the potential sources or the temporal variability of pollution.We used detailed information on individuals' exposure to various pollutants measured at fine spatiotemporal scale to obtain more reliable effect estimates. A panel of 115 patients was followed up for an average continuous period of 128 days carrying a personal monitor specifically designed for this project that measured temperature, nitrogen dioxide (NO2), ozone (O3), nitric oxide (NO), carbon monoxide (CO), and particulate matter with aerodynamic diameter <2.5 and <10 µm at 1-min time resolution. Each patient recorded daily information on respiratory symptoms and measured peak expiratory flow (PEF). A pulmonologist combined related data to define a binary variable denoting an "exacerbation". The exposure-response associations were assessed with mixed effects models.We found that gaseous pollutants were associated with a deterioration in patients' health. We observed an increase of 16.4% (95% CI 8.6-24.6%), 9.4% (95% CI 5.4-13.6%) and 7.6% (95% CI 3.0-12.4%) in the odds of exacerbation for an interquartile range increase in NO2, NO and CO, respectively. Similar results were obtained for cough and sputum. O3 was found to have adverse associations with PEF and breathlessness. No association was observed between particulate matter and any outcome.Our findings suggest that, when considering total personal exposure to air pollutants, mainly the gaseous pollutants affect COPD patients' health.

Difference in ambient-personal exposure to PM2.5 and its inflammatory effect in local residents in urban and peri-urban Beijing, China: results of the AIRLESS project.

Measurement of ambient fine particulate matter (PM2.5) is often used as a proxy of personal exposure in epidemiological studies. However, the difference between personal and ambient exposure, and whether it biases the estimates of health effects remain unknown. Based on an epidemiological study (AIRLESS) and simultaneously launched intensive monitoring campaigns (APHH), we quantified and compared the personal and ambient exposure to PM2.5 and the related health impact among residents in Beijing, China. In total, 123 urban and 128 peri-urban non-smoking participants were recruited from two well-established cohorts in Beijing. During winter 2016 and summer 2017, each participant was instructed to carry a validated personal air monitor (PAM) to measure PM2.5 concentration at high spatiotemporal resolution for seven consecutive days in each season. Multiple inflammatory biomarkers were measured, including exhaled NO, blood monocytes counts and C-reactive protein. Linear mixed-effect models were used for the associations between exposure and health outcomes with adjustment for confounders. The average level of daily personal exposure to PM2.5 was consistently lower than using corresponding ambient concentration, and the difference is greater during the winter. The personal to ambient (P/A) ratio of exposure to PM2.5 exhibited an exponentially declining trend, and showed larger variations when ambient PM2.5 levels < 25 µg m-3. Personal exposure to PM2.5 was significantly associated with the increase in respiratory and systemic inflammatory biomarkers; however, the associations were weaker or became insignificant when ambient concentrations were used. Exposure to ambient PM2.5 might not be a good proxy to estimate the health effect of exposure to personal PM2.5.

Chemical Investigation of Household Solid Fuel Use and Outdoor Air Pollution Contributions to Personal PM2.5 Exposures.

In communities with household solid fuel use, transitioning to clean stoves/fuels often results in only moderate reductions in fine particulate matter (PM2.5) exposures; the chemical composition of those exposures may help explain why. We collected personal exposure (men and women) and outdoor PM2.5 samples in villages in three Chinese provinces (Shanxi, Beijing, and Guangxi) and measured chemical components, including water-soluble organic carbon (WSOC), ions, elements, and organic tracers. Source contributions from chemical mass balance modeling (biomass burning, coal combustion, vehicles, dust, and secondary inorganic aerosol) were similar between outdoor and personal PM2.5 samples. Principal component analysis of organic and inorganic components identified analogous sources, including a regional ambient source. Chemical components of PM2.5 exposures did not differ significantly by gender. Participants using coal had higher personal/outdoor (P/O) ratios of coal combustion tracers (picene, sulfate, As, and Pb) than those not using coal, but no such trend was observed for biomass burning tracers (levoglucosan, K+, WSOC). Picene and most levoglucosan P/O ratios exceeded 1 even among participants not using coal and biomass, respectively, indicating substantial indirect exposure to solid fuel emissions from other homes. Contributions of community-level emissions to exposures suggest that meaningful exposure reductions will likely require extensive fuel use changes within communities.

Detection of Microplastics in Ambient Particulate Matter Using Raman Spectral Imaging and Chemometric Analysis.

Microplastics have been observed in indoor and outdoor air. This raises concern for human exposure, especially should they occur in small enough sizes, which if inhaled, reach the central airway and distal lung. As yet, methods for their detection have not spectroscopically verified the chemical composition of microplastics in this size-range. One proposed method is an automated spectroscopic technique, Raman spectral imaging; however, this generates large and complex data sets. This study aims to optimize Raman spectral imaging for the identification of microplastics (≥2 µm) in ambient particulate matter, using different chemometric techniques. We show that Raman spectral images analyzed using chemometric statistical approaches are appropriate for the identification of both virgin and environmental microplastics ≥2 µm in size. On the basis of the sensitivity, we recommend using the developed Pearson's correlation and agglomerative hierarchical cluster analysis for the identification of microplastics in spectral data sets. Finally, we show their applicability by identifying airborne microplastics >4.7 µm in an outdoor particulate matter sample obtained at an urban sampling site in London, United Kingdom. This semiquantitative method will enable the procurement of exposure concentrations of airborne microplastics guiding future toxicological assessments.

Toxicity of airborne particles-established evidence, knowledge gaps and emerging areas of importance.

Epidemiological research has taught us a great deal about the health effects of airborne particulate matter (PM), particularly cardiorespiratory effects of combustion-related particles. This has been matched by toxicological research to define underlying mechanistic pathways. To keep abreast of the substantial challenges that air pollution continues to throw at us requires yet more strides to be achieved. For example, being aware of the most toxic components/sources and having a definitive idea of the range of associated disease outcomes. This review discusses approaches designed to close some of these knowledge gaps. These include a focus on particles arising from non-exhaust PM at the roadside and microplastics-both of which are becoming more relevant in the light of a shift in PM composition in response to global pressure to reduce combustion emissions. The application of hypothesis-free approaches in both mechanistic studies and epidemiology in unveiling unexpected relationships and generating novel insights is also discussed. Previous work, strengthening the evidence for both the adverse effects and benefits of intervention tell us that the sooner we act to close knowledge gaps, increase awareness and develop creative solutions, the sooner we can reduce the public health burden attributable to these complex and insidious environmental pollutants. This article is part of a discussion meeting issue 'Air quality, past present and future'.

Respiratory and cardiovascular responses to walking down a traffic-polluted road compared with walking in a traffic-free area in participants aged 60 years and older with chronic lung or heart disease and age-matched healthy controls: a randomised, crossover study.

BACKGROUND: Long-term exposure to pollution can lead to an increase in the rate of decline of lung function, especially in older individuals and in those with chronic obstructive pulmonary disease (COPD), whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD. We aimed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults. METHODS: In this randomised, crossover study, we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease (GOLD) COPD who had been clinically stable for 6 months, and age-matched healthy volunteers. Individuals with ischaemic heart disease or COPD were recruited from existing databases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing databases. All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants' doctors during the study. Participants were randomly assigned by drawing numbered disks at random from a bag to do a 2 h walk either along a commercial street in London (Oxford Street) or in an urban park (Hyde Park). Baseline measurements of participants were taken before the walk in the hospital laboratory. During each walk session, black carbon, particulate matter (PM) concentrations, ultrafine particles, and nitrogen dioxide (NO2) concentrations were measured. FINDINGS: Between October, 2012, and June, 2014, we screened 135 participants, of whom 40 healthy volunteers, 40 individuals with COPD, and 39 with ischaemic heart disease were recruited. Concentrations of black carbon, NO2, PM10, PM2.5, and ultrafine particles were higher on Oxford Street than in Hyde Park. Participants with COPD reported more cough (odds ratio [OR] 1·95, 95% CI 0·96-3·95; p<0·1), sputum (3·15, 1·39-7·13; p<0·05), shortness of breath (1·86, 0·97-3·57; p<0·1), and wheeze (4·00, 1·52-10·50; p<0·05) after walking down Oxford Street compared with Hyde Park. In all participants, irrespective of their disease status, walking in Hyde Park led to an increase in lung function (forced expiratory volume in the first second [FEV1] and forced vital capacity [FVC]) and a decrease in pulse wave velocity (PWV) and augmentation index up to 26 h after the walk. By contrast, these beneficial responses were attenuated after walking on Oxford Street. In participants with COPD, a reduction in FEV1 and FVC, and an increase in R5-20 were associated with an increase in during-walk exposure to NO2, ultrafine particles and PM2.5, and an increase in PWV and augmentation index with NO2 and ultrafine particles. In healthy volunteers, PWV and augmentation index were associated both with black carbon and ultrafine particles. INTERPRETATION: Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD, ischaemic heart disease, and those free from chronic cardiopulmonary diseases. Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease. Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects. FUNDING: British Heart Foundation.

Raman Spectral Imaging for the Detection of Inhalable Microplastics in Ambient Particulate Matter Samples.

Microplastics are ubiquitous contaminants, with preliminary evidence indicating they are a novel component of air pollution. This presents a plausible inhalation exposure pathway, should microplastics occur in the inhalable size range; however, this remains an analytical challenge. Here, we develop a filter-based sampling method compatible with both air quality monitoring and Raman spectral imaging (RSI) for the detection of inhalable-sized microplastics. Clean and particulate matter (PM) contaminated filters of a range of compositions were screened. RSI was validated using a plastic microbead suspension (poly(methyl methacrylate) (5-27 µm), polyethylene (10-27 µm), and polystyrene (4 and 10 µm)). Filters were loaded with the suspension before being analyzed. RSI analysis was conducted using a univariate analysis, fitting unique plastic bands to the spectral data sets, where high spatial intensity indicated the presence of microplastics. Inhalable microplastics were not visibly detectable against quartz or spectroscopically detectable against polytetrafluoroethylene (PTFE)- and alumina-based filters. While microplastics were detectable against cellulose, the PM-contaminated filters (4 and 24 h) burned during analysis. The greatest intensities for microplastics were observed against the silver membrane filter, and inhalable microplastics were still detectable in a 24 h PM sample. These findings will facilitate the acquisition of inhalable microplastic concentrations, which are necessary for understanding microplastic exposure and, ultimately, what their potential role in PM-associated health effects might be.

Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes.

Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) -stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T-lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naive CD8 T-cell responses. Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow cytometry after stimulation with UPMin vitro in the presence/absence of granulocyte-macrophage colony-stimulating factor (GM-CSF). The capacity of these mDCs to stimulate naive CD8 T-lymphocyte responses in allogeneic co-culture was then assessed by measuring T-cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon-γ (IFN-γ)-producing T lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of mDCs enhanced CD8 T-cell proliferation and the frequency of IFN-γ+ cells. The secretion of tumour necrosis factor-α, interleukin-13, Granzyme A and Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced many of these T-cell functions. The PM-induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and increases production of pro-inflammatory cytokines. Such UPM-induced stimulation of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.

Cys34 Adductomes Differ between Patients with Chronic Lung or Heart Disease and Healthy Controls in Central London.

Oxidative stress generates reactive species that modify proteins, deplete antioxidant defenses, and contribute to chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD). To determine whether protein modifications differ between COPD or IHD patients and healthy subjects, we performed untargeted analysis of adducts at the Cys34 locus of human serum albumin (HSA). Biospecimens were obtained from nonsmoking participants from London, U.K., including healthy subjects (n = 20) and patients with COPD (n = 20) or IHD (n = 10). Serum samples were digested with trypsin and analyzed by liquid chromatography-high resolution mass spectrometry. Effects of air pollution on adduct levels were also investigated based on estimated residential exposures to PM2.5, O3 and NO2. For the 39 adducts with sufficient data, levels were essentially identical in blood samples collected from the same subjects on two consecutive days, consistent with the 28 day residence time of HSA. Multivariate linear regression revealed 21 significant associations, mainly with the underlying diseases but also with air-pollution exposures (p-value < 0.05). Interestingly, most of the associations indicated that adduct levels decreased with the presence of disease or increased pollutant concentrations. Negative associations of COPD and IHD with the Cys34 disulfide of glutathione and two Cys34 sulfoxidations, were consistent with previous results from smoking and nonsmoking volunteers and nonsmoking women exposed to indoor combustion of coal and wood.

Land use regression models for the oxidative potential of fine particles (PM2.5) in five European areas.

Oxidative potential (OP) of particulate matter (PM) is proposed as a biologically-relevant exposure metric for studies of air pollution and health. We aimed to evaluate the spatial variability of the OP of measured PM2.5 using ascorbate (AA) and (reduced) glutathione (GSH), and develop land use regression (LUR) models to explain this spatial variability. We estimated annual average values (m-3) of OPAA and OPGSH for five areas (Basel, CH; Catalonia, ES; London-Oxford, UK (no OPGSH); the Netherlands; and Turin, IT) using PM2.5 filters. OPAA and OPGSH LUR models were developed using all monitoring sites, separately for each area and combined-areas. The same variables were then used in repeated sub-sampling of monitoring sites to test sensitivity of variable selection; new variables were offered where variables were excluded (p > .1). On average, measurements of OPAA and OPGSH were moderately correlated (maximum Pearson's maximum Pearson's R = = .7) with PM2.5 and other metrics (PM2.5absorbance, NO2, Cu, Fe). HOV (hold-out validation) R2 for OPAA models was .21, .58, .45, .53, and .13 for Basel, Catalonia, London-Oxford, the Netherlands and Turin respectively. For OPGSH, the only model achieving at least moderate performance was for the Netherlands (R2 = .31). Combined models for OPAA and OPGSH were largely explained by study area with weak local predictors of intra-area contrasts; we therefore do not endorse them for use in epidemiologic studies. Given the moderate correlation of OPAA with other pollutants, the three reasonably performing LUR models for OPAA could be used independently of other pollutant metrics in epidemiological studies.

Oxidative potential (OP) and mineralogy of iron ore particulate matter at the Gol-E-Gohar Mining and Industrial Facility (Iran).

Concentrations of total suspended particulate matter, particulate matter with aerodynamic diameter <2.5 µm (PM2.5), particulate matter <10 µm (PM10), and fallout dust were measured at the Iranian Gol-E-Gohar Mining and Industrial Facility. Samples were characterized in terms of mineralogy, morphology, and oxidative potential. Results show that indoor samples exceeded the 24-h PM2.5 and PM10 mass concentration limits (35 and 150 µg m-3, respectively) set by the US National Ambient Air Quality Standards. Calcite, magnetite, tremolite, pyrite, talc, and clay minerals such as kaolinite, vermiculite, and illite are the major phases of the iron ore PM. Accessory minerals are quartz, dolomite, hematite, actinolite, biotite, albite, nimite, laumontite, diopside, and muscovite. The scanning electron microscope structure of fibrous-elongated minerals revealed individual fibers in the range of 1.5 nm to 71.65 µm in length and 0.2 nm to 3.7 µm in diameter. The presence of minerals related to respiratory diseases, such as talc, crystalline silica, and needle-shaped minerals like amphibole asbestos (tremolite and actinolite), strongly suggests the need for detailed health-based studies in the region. The particulate samples show low to medium oxidative potential per unit of mass, in relation to an urban road side control, being more reactive with ascorbate than with glutathione or urate. However, the PM oxidative potential per volume of air is exceptionally high, confirming that the workers are exposed to a considerable oxidative environment. PM released by iron ore mining and processing activities should be considered a potential health risk to the mine workers and nearby employees, and strategies to combat the issue are suggested.