Associations between daily mortality in London and combined oxidant capacity, ozone and nitrogen dioxide.

Both nitrogen dioxide (NO2) and ozone (O3) are powerful oxidants in ambient air that are intimately linked through atmospheric chemistry and which continuously interchange over very short timescales. Based upon atmospheric chemistry alone, there is a strong, a priori, reason for considering O3 and NO2 together in epidemiological studies, rather than either of the two pollutants separately in single-pollutant models. This paper compares two approaches to this, using Ox, defined as O3 + NO2, as a single metric and also using O3 and NO2 together in two-pollutant models. We hypothesised that the magnitude of the association between Ox and daily mortality would be greater than for NO2 and O3 individually. Using collocated hourly measurements for O3 and NO2 in London, from 2000 to 2005, we carried out a time series analysis of daily mortality. We investigated O3, NO2 and Ox individually in single-pollutant Poisson regression models and NO2 and O3 jointly in two-pollutant models in both all-year and season-specific analyses. We observed larger associations for mean 24-h concentrations of Ox (1.30 % increase in mortality per 10 ppb) than for O3 (0.87 %) and NO2 (0 %) individually. However, when analysed jointly in two-pollutant models, associations for O3 (1.54 %) and NO2 (1.07 %) were comparable to the Ox association. Season-specific analyses broadly followed this pattern irrespective of whether the Ox concentrations were driven by O3 production (summer) or depletion (winter). This novel approach in air pollution epidemiology captures the simultaneous impact of both oxidants whilst avoiding many of the statistical issues associated with two-pollutant models and potentially simplifies health impact calculations

Role of oxidative stress in cardiovascular disease outcomes following exposure to ambient air pollution

Exposure to ambient air pollution is associated with adverse cardiovascular outcomes. These are manifested through several, likely overlapping, pathways including at the functional level, endothelial dysfunction, atherosclerosis, pro-coagulation and alterations in autonomic nervous system balance and blood pressure. At numerous points within each of these pathways, there is potential for cellular oxidative imbalances to occur. The current review examines epidemiological, occupational and controlled exposure studies and research employing healthy and diseased animal models, isolated organs and cell cultures in assessing the importance of the pro-oxidant potential of air pollution in the development of cardiovascular disease outcomes. The collective body of data provides evidence that oxidative stress (OS) is not only central to eliciting specific cardiac endpoints, but is also implicated in modulating the risk of succumbing to cardiovascular disease, sensitivity to ischemia/reperfusion injury and the onset and progression of metabolic disease following ambient pollution exposure. To add to this large research effort conducted to date, further work is required to provide greater insight into areas such as (a) whether an oxidative imbalance triggers and/or worsens the effect and/or is representative of the consequence of disease progression, (b) OS pathways and cardiac outcomes caused by individual pollutants within air pollution mixtures, or as a consequence of inter-pollutant interactions and (c) potential protection provided by nutritional supplements and/or pharmacological agents with antioxidant properties, in susceptible populations residing in polluted urban cities

Sex Differences in Glutathione Peroxidase Activity and Central Obesity in Patients with Type 2 Diabetes at High Risk of Cardio-Renal Disease.

Women with type 2 diabetes (T2DM) have an increased susceptibility of developing cardio-renal disease compared to men, the reasons and the mechanisms of this vulnerability are unclear. Since oxidative stress plays a key role in the development of cardio-renal disease, we investigated the relationship between sex, plasma antioxidants status (glutathione peroxidase (GPx-3 activity), vitamin E and selenium), and adiposity in patients with T2DM at high risk of cardio-renal disease. Women compared to men had higher GPx-3 activity (p = 0.02), bio-impedance (p ≤ 0.0001), and an increase in waist circumference in relation to recommended cut off-points (p = 0.0001). Waist circumference and BMI were negatively correlated with GPx-3 activity (p ≤ 0.05 and p ≤ 0.01, respectively) and selenium concentration (p ≤ 0.01 and p ≤ 0.02, respectively). In multiple regression analysis, waist circumference and sex were independent predictors of GPx-3 activity (p ≤ 0.05 and p ≤ 0.05, respectively). The data suggest that increased central fat deposits are associated with reduced plasma antioxidants which could contribute to the future risk of cardio-renal disease. The increased GPx-3 activity in women could represent a preserved response to the disproportionate increase in visceral fat. Future studies should be aimed at evaluating if the modulation of GPx-3 activity reduces cardio-renal risk in men and women with T2DM

Mechanisms underlying the health effects of desert sand dust

Desertification and climate change indicate a future expansion of the global area of dry land and an increase in the risk of drought. Humans may therefore be at an ever-increasing risk of frequent exposure to, and resultant adverse health effects of desert sand dust. This review appraises a total of 52 experimental studies that have sought to identify mechanisms and intermediate endpoints underlying epidemiological evidence of an impact of desert dust on cardiovascular and respiratory health. Toxicological studies, in main using doses that reflect or at least approach real world exposures during a dust event, have demonstrated that virgin sand dust particles and dust storm particles sampled at remote locations away from the source induce inflammatory lung injury and aggravate allergen-induced nasal and pulmonary eosinophilia. Effects are orchestrated by cytokines, chemokines and antigen-specific immunoglobulin potentially via toll-like receptor/myeloid differentiation factor signaling pathways. Findings suggest that in addition to involvement of adhered chemical and biological pollutants, mineralogical components may also be implicated in the pathogenesis of human respiratory disorders during a dust event. Whilst comparisons with urban particulate matter less than 2.5 μm in diameter (PM2.5) suggest that allergic inflammatory responses are greater for microbial element-rich dust- PM2.5, aerosols generated during dust events appear to have a lower oxidative potential compared to combustion-generated PM2.5 sampled during non-dust periods. In vitro findings suggest that the significant amounts of suspended desert dust during storm periods may provide a platform to intermix with chemicals on its surfaces, thereby increasing the bioreactivity of PM2.5 during dust storm episodes, and that mineral dust surface reactions are an unrecognized source of toxic organic chemicals in the atmosphere, enhancing toxicity of aerosols in urban environments. In summary, the experimental research on desert dust on respiratory endpoints go some way in clarifying the mechanistic effects of atmospheric desert dust on the upper and lower human respiratory system. In doing so, they provide support for biological plausibility of epidemiological associations between this particulate air pollutant and events including exacerbation of asthma, hospitalization for respiratory infections and seasonal allergic rhinitis

Global nature of airborne particle toxicity and health effects: a focus on megacities, wildfires, dust storms and residential biomass burning

Since air pollutants are difficult and expensive to control, a strong scientific underpinning to policies is needed to guide mitigation aimed at reducing the current burden on public health. Much of the evidence concerning hazard identification and risk quantification related to air pollution comes from epidemiological studies. This must be reinforced with mechanistic confirmation to infer causality. In this review we focus on data generated from four contrasting sources of particulate air pollution that result in high population exposures and thus where there remains an unmet need to protect health: urban air pollution in developing megacities, household biomass combustion, wildfires and desert dust storms. Taking each in turn, appropriate measures to protect populations will involve advocating smart cities and addressing economic and behavioural barriers to sustained adoption of clean stoves and fuels. Like all natural hazards, wildfires and dust storms are a feature of the landscape that cannot be removed. However, many efforts from emission containment (land/fire management practices), exposure avoidance and identifying susceptible populations can be taken to prepare for air pollution episodes and ensure people are out of harm’s way when conditions are life-threatening. Communities residing in areas affected by unhealthy concentrations of any airborne particles will benefit from optimum communication via public awareness campaigns, designed to empower people to modify behaviour in a way that improves their health as well as the quality of the air they breathe

Combustion of dried animal dung as biofuel results in the generation of highly redox active fine particulates.

BACKGROUND: The burning of biomass in the developing world for heating and cooking results in high indoor particle concentrations. Long-term exposure to airborne particulate matter (PM) has been associated with increased rates of acute respiratory infections, chronic obstructive lung disease and cancer. In this study we determined the oxidative activity of combustion particles derived from the biomass fuel dung cake by examining their capacity to deplete antioxidants from a model human respiratory tract lining fluid (RTLF). For comparison, the observed oxidative activity was compared with that of particles derived from industrial and vehicular sources. RESULTS: Incubation of the dung cake particle suspensions in the RTLF for 4 h resulted in a mean loss of ascorbate of 72.1 +/- 0.7 and 89.7 +/- 2.5% at 50 and 100 microg/ml, respectively. Reduced glutathione was depleted by 49.6 +/- 4.3 and 63.5 +/- 22.4% under the same conditions. The capacity of these samples to deplete ascorbate was in excess of that observed with diesel or gasoline particles, but comparable to that seen with residual oil fly ash and considerably in excess of all three control particles in terms of glutathione depletion. Co-incubation with the metal chelator diethylenetriaminepentaacetate inhibited these losses, whilst minimal inhibition was seen with superoxide dismutase and catalase treatment. The majority of the activity observed appeared to be contained within aqueous particle extracts. CONCLUSION: These data demonstrate that biomass derived particles have considerable oxidative activity, largely attributable to their transition metal content

Dynamic compression can inhibit chondrogenesis of mesenchymal stem cells

Funding was provided by Science Foundation Ireland (07-RFP-ENMF142) and Enterprise Ireland (PC/2006/384)

An automated online instrument to quantify aerosol-bound reactive oxygen species (ROS) for ambient measurement and health-relevant aerosol studies

The adverse health effects associated with ambient aerosol particles have been well documented, but it is still unclear which aerosol properties are most important for their negative health impact. Some studies suggest the oxidative effects of particle-bound reactive oxygen species (ROS) are potential major contributors to the toxicity of particles. Traditional ROS measurement techniques are labour-intensive, give poor temporal resolution and generally have significant delays between aerosol sampling and ROS analysis. However, many oxidising particle components are reactive and thus potentially short-lived. Thus, a technique to quantify particle-bound ROS online would be beneficial to quantify also the short-lived ROS components. We introduce a new portable instrument to allow online, continuous measurement of particle-bound ROS using a chemical assay of 2$^\prime$7$^\prime$-dichlorofluorescein (DCFH) with horseradish peroxidase (HRP), via fluorescence spectroscopy. All components of the new instrument are attached to a containing shell, resulting in a compact system capable of automated continuous field deployment over many hours or days. From laboratory measurements, the instrument was found to have a detection limit of ~4 nmol [H$_2$O$_2$] equivalents per cubic metre (m$^3$) air, a dynamic range up to at least ~2000 nmol [H$_2$O$_2$] equivalents per m$^3$ air and a time resolution of ≤ 12 min. The instrument allows for ~16 h automated measurement if unattended and shows a fast response to changes in concentrations of laboratory-generated oxidised organic aerosol. The instrument was deployed at an urban site in London, and particulate ROS levels of up to 24 nmol [H$_2$O$_2$] equivalents per m$^3$ air were detected with PM$_{2.5}$ concentrations up to 28 µg m$^{−3}$. The new and portable Online Particle-bound ROS Instrument (OPROSI) allows fast-response quantification; this is important due to the potentially short-lived nature of particle-bound ROS as well as fast-changing atmospheric conditions, especially in urban environments. The instrument design allows for automated operation and extended field operation with twice-daily presence of an operator. As well as having sensitivity suitable for ambient level measurement, the instrument is also suitable at concentrations such as those required for laboratory and chamber toxicological studies.The authors would like to thank ERC (the European Research Council, grant no. 279405) for their funding of this study. Infrastructure at Marylebone Road was supported by NERC (the Natural Environment Research Council, Clearflo grant no. NE/H003231/1) and Defra (Department of Environment Food and Rural Affairs, contract AQ0643 Automatic London Network (2010-14) RMP 5442)

The role of burden of disease assessment in tracking progress towards achieving WHO global air quality guidelines

OBJECTIVES: More than 90% of the global population live in areas exceeding the PM2.5 air quality guidelines (AQGs). We provide an overview of the ambient PM2.5-related burden of disease (BoD) studies along with scenario analysis in the framework of the WHO AQG update on the estimated reduction in the BoD if AQGs were achieved globally. METHODS: We reviewed the literature for large-scale studies for the BoD attributed to ambient PM2.5. Moreover, we used the latest WHO statistics to calculate the BoD at current levels and the scenarios of aligning with interim targets and AQG levels. RESULTS: The most recent BoD studies (2010 onwards) share a similar methodology, but there are differences in the input data which affect the estimates for attributable deaths (2.9-8.9 million deaths annually). Moreover, we found that if AQGs were achieved, the estimated BoD would be reduced by up to 50% in total deaths worldwide. CONCLUSIONS: Understanding the BoD across countries, especially in those that do not align with the AQGs, is essential in order to inform actions to reduce air pollution globally