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"Kelly, Frank J."
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Air pollution and public health: emerging hazards and improved understanding of risk
Despite past improvements in air quality, very large parts of the population in urban areas breathe air that does not meet European standards let alone the health-based World Health Organisation Air Quality Guidelines. Over the last 10 years, there has been a substantial increase in findings that particulate matter (PM) air pollution is not only exerting a greater impact on established health endpoints, but is also associated with a broader number of disease outcomes. Data strongly suggest that effects have no threshold within the studied range of ambient concentrations, can occur at levels close to PM₂.₅ background concentrations and that they follow a mostly linear concentration–response function. Having firmly established this significant public health problem, there has been an enormous effort to identify what it is in ambient PM that affects health and to understand the underlying biological basis of toxicity by identifying mechanistic pathways—information that in turn will inform policy makers how best to legislate for cleaner air. Another intervention in moving towards a healthier environment depends upon the achieving the right public attitude and behaviour by the use of optimal air pollution monitoring, forecasting and reporting that exploits increasingly sophisticated information systems. Improving air quality is a considerable but not an intractable challenge. Translating the correct scientific evidence into bold, realistic and effective policies undisputedly has the potential to reduce air pollution so that it no longer poses a damaging and costly toll on public health.
Journal Article
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.
Journal Article
Are noise and air pollution related to the incidence of dementia? A cohort study in London, England
ObjectiveTo investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London.DesignRetrospective cohort study using primary care data.Setting75 Greater London practices.Participants130 978 adults aged 50–79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence.Primary and secondary outcome measuresA first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer’s disease and vascular dementia during 2005–2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.Results2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer’s disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2 concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5 specifically from primary traffic sources only and Lnight, but only NO2 and PM2.5 remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer’s disease than vascular dementia.ConclusionsWe have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.
Journal Article
Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter
Particulate matter (PM) pollutant exposure, which induces oxidative stress and inflammation, and vitamin D insufficiency, which compromises immune regulation, are detrimental in asthma.
Mechanistic cell culture experiments were undertaken to ascertain whether vitamin D abrogates PM-induced inflammatory responses of human bronchial epithelial cells (HBECs) through enhancement of antioxidant pathways.
Transcriptome analysis, PCR and ELISA were undertaken to delineate markers of inflammation and oxidative stress; with comparison of expression in primary HBECs from healthy and asthmatic donors cultured with reference urban PM in the presence/absence of vitamin D.
Transcriptome analysis identified over 500 genes significantly perturbed by PM-stimulation, including multiple pro-inflammatory cytokines. Vitamin D altered expression of a subset of these PM-induced genes, including suppressing IL6. Addition of vitamin D suppressed PM-stimulated IL-6 production, although to significantly greater extent in healthy versus asthmatic donor cultures. Vitamin D also differentially affected PM-stimulated GM-CSF, with suppression in healthy HBECs and enhancement in asthmatic cultures. Vitamin D increased HBEC expression of the antioxidant pathway gene G6PD, increased the ratio of reduced to oxidised glutathione, and in PM-stimulated cultures decreased the formation of 8-isoprostane. Pre-treatment with vitamin D decreased CXCL8 and further decreased IL-6 production in PM-stimulated cultures, an effect abrogated by inhibition of G6PD with DHEA, supporting a role for this pathway in the anti-inflammatory actions of vitamin D.
In a study using HBECs from 18 donors, vitamin D enhanced HBEC antioxidant responses and modulated the immune response to PM, suggesting that vitamin D may protect the airways from pathological pollution-induced inflammation.
Journal Article
Potential health benefits of eliminating traffic emissions in urban areas
Traffic is one of the major contributors to PM
2.5
in cities worldwide. Quantifying the role of traffic is an important step towards understanding the impact of transport policies on the possibilities to achieve cleaner air and accompanying health benefits. With the aim of estimating potential health benefits of eliminating traffic emissions, we carried out a meta-analysis using the World Health Organisation (WHO) database of source apportionment studies of PM
2.5
concentrations. Specifically, we used a Bayesian meta-regression approach, modelling both overall and traffic-related (tailpipe and non-tailpipe) concentrations simultaneously. We obtained the distributions of expected PM
2.5
concentrations (posterior densities) of different types for 117 cities worldwide. Using the non-linear Integrated Exposure Response (IER) function of PM
2.5
, we estimated percent reduction in different disease endpoints for a scenario with complete removal of traffic emissions. We found that eliminating traffic emissions results in achieving the WHO-recommended concentration of PM
2.5
only for a handful of cities that already have low concentrations of pollution. The percentage reduction in premature mortality due to cardiovascular and respiratory diseases increases up to a point (30–40 ug/m
3
), and above this concentration, it flattens off. For diabetes-related mortality, the percentage reduction in mortality decreases with increasing concentrations—a trend that is opposite to other outcomes. For cities with high concentrations of pollution, the results highlight the need for multi-sectoral strategies to reduce pollution. The IER functions of PM
2.5
result in diminishing returns of health benefits at high concentrations, and in case of diabetes, there are even negative returns. The results show the significant effect of the shape of IER functions on health benefits. Overall, despite the diminishing results, a significant burden of deaths can be prevented by policies that aim to reduce traffic emissions even at high concentrations of pollution.
Journal Article
Long-Term Exposure to Primary Traffic Pollutants and Lung Function in Children: Cross-Sectional Study and Meta-Analysis
There is widespread concern about the possible health effects of traffic-related air pollution. Nitrogen dioxide (NO2) is a convenient marker of primary pollution. We investigated the associations between lung function and current residential exposure to a range of air pollutants (particularly NO2, NO, NOx and particulate matter) in London children. Moreover, we placed the results for NO2 in context with a meta-analysis of published estimates of the association.
Associations between primary traffic pollutants and lung function were investigated in 4884 children aged 9-10 years who participated in the Child Heart and Health Study in England (CHASE). A systematic literature search identified 13 studies eligible for inclusion in a meta-analysis. We combined results from the meta-analysis with the distribution of the values of FEV1 in CHASE to estimate the prevalence of children with abnormal lung function (FEV1<80% of predicted value) expected under different scenarios of NO2 exposure. In CHASE, there were non-significant inverse associations between all pollutants except ozone and both FEV1 and FVC. In the meta-analysis, a 10 μg/m3 increase in NO2 was associated with an 8 ml lower FEV1 (95% CI: -14 to -1 ml; p: 0.016). The observed effect was not modified by a reported asthma diagnosis. On the basis of these results, a 10 μg/m3 increase in NO2 level would translate into a 7% (95% CI: 4% to 12%) increase of the prevalence of children with abnormal lung function.
Exposure to traffic pollution may cause a small overall reduction in lung function and increase the prevalence of children with clinically relevant declines in lung function.
Journal Article
Respiratory Health Effects of Airborne Particulate Matter: The Role of Particle Size, Composition, and Oxidative Potential — The RAPTES Project
BACKGROUND: Specific characteristics of particulate matter (PM) responsible for associations with respiratory health observed in epidemiological studies are not well established. High correlations among, and differential measurement errors of, individual components contribute to this uncertainty. OBJECTIVES: We investigated which characteristics of PM have the most consistent associations with acute changes in respiratory function in healthy volunteers. METHODS: We used a semiexperimental design to accurately assess exposure. We increased exposure contrast and reduced correlations among PM characteristics by exposing volunteers at five different locations: an underground train station, two traffic sites, a farm, and an urban background site. Each of the 31 participants was exposed for 5 hr while exercising intermittendy, three to seven times at different locations during March— October 2009. We measured PM₁₀ , PM₂.₅, particle number concentrations (PNC), absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and PM oxidative potential. Lung function [FEV₁ (forced expiratory volume in 1 sec), FVC (forced vital capacity), FEF₂₅_₇₅ (forced expiratory flow at 25-75% of vital capacity), and PEF (peak expiratory flow)] and fractional exhaled nitric oxide (FENQ) were measured before and at three time points after exposure. Data were analyzed with mixed linear regression. RESULTS: An interquartile increase in PNC (33,000 particles/cm³) was associated with an 11% [95% confidence interval (CI): 5, 17%] and 12% (95% CI: 6, 17%) FENO increase over baseline immediately and at 2 hr postexposure, respectively. A 7% (95% CI: 0.5, 14%) increase persisted until the following morning. These associations were robust and insensitive to adjustment for other pollutants. Similarly consistent associations were seen between FVC and FEV₁ with PNC, NO₂ (nitrogen dioxide), and NOX (nitrogen oxides). CONCLUSIONS: Changes in PNC, NO₂, and NOX were associated with evidence of acute airway inflammation (i. e., FENO) and impaired lung function. PM mass concentration and PM₁₀ oxidative potential were not predictive of the observed acute responses.
Journal Article
Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers
Introduction We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects. Methods We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm and an urban background site. Each volunteer visited at least three sites. We conducted health measurements before exposure, 2 h after exposure and the next morning. We measured air pollution on site and characterised the OP of PM2.5 and PM10 using three a-cellular assays; dithiotreitol (OPDTT), electron spin resonance (OPESR) and ascorbic acid depletion (OPAA). Results In single-pollutant models, all measures of OP were significantly associated with increases in fractional exhaled nitric oxide and increases in interleukin-6 in nasal lavage 2 h after exposure. These OP associations remained significant after adjustment for co-pollutants when only the four outdoor sites were included, but lost significance when measurements at the underground site were included. Other health end points including lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Conclusions We found significant associations between three a-cellular measures of OP of PM and markers of airway and nasal inflammation. However, consistency of these effects in two-pollutant models depended on how measurements at the underground site were considered. Lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Our study, therefore, provides limited support for a role of OP in predicting acute health effects of PM in healthy young adults.
Journal Article
Short-term exposure to traffic-related air pollution and daily mortality in London, UK
Epidemiological studies have linked daily concentrations of urban air pollution to mortality, but few have investigated specific traffic sources that can inform abatement policies. We assembled a database of >100 daily, measured and modelled pollutant concentrations characterizing air pollution in London between 2011 and 2012. Based on the analyses of temporal patterns and correlations between the metrics, knowledge of local emission sources and reference to the existing literature, we selected,
a priori
, markers of traffic pollution: oxides of nitrogen (general traffic); elemental and black carbon (EC/BC) (diesel exhaust); carbon monoxide (petrol exhaust); copper (tyre), zinc (brake) and aluminium (mineral dust). Poisson regression accounting for seasonality and meteorology was used to estimate the percentage change in risk of death associated with an interquartile increment of each pollutant. Associations were generally small with confidence intervals that spanned 0% and tended to be negative for cardiovascular mortality and positive for respiratory mortality. The strongest positive associations were for EC and BC adjusted for particle mass and respiratory mortality, 2.66% (95% confidence interval: 0.11, 5.28) and 2.72% (0.09, 5.42) per 0.8 and 1.0
μ
g/m
3
, respectively. These associations were robust to adjustment for other traffic metrics and regional pollutants, suggesting a degree of specificity with respiratory mortality and diesel exhaust containing EC/BC.
Journal Article