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Details of Award

NERC Reference : NE/T001895/2

Component-Specific Air pollutant Drivers of Disease Risk in Early to Midlife: a pathway approach. (DREaM)

Grant Award

Principal Investigator:
Dr IS Mudway, Imperial College London, School of Public Health
Co-Investigator:
Professor P Vineis, Imperial College London, School of Public Health
Co-Investigator:
Professor B Castellani, Durham University, Sociology
Co-Investigator:
Dr Q Chan, Imperial College London, School of Public Health
Co-Investigator:
Dr D Fecht, Imperial College London, School of Public Health
Co-Investigator:
Dr SD Beevers, Imperial College London, School of Public Health
Co-Investigator:
Dr B Barratt, Imperial College London, School of Public Health
Science Area:
Atmospheric
Overall Classification:
Unknown
ENRIs:
Environmental Risks and Hazards
Science Topics:
Environment & Health
Environmental Genomics
Pollution
Atmospheric aerosols
Epigenetics
Methylation
Epigenetics
Population Genetics/Evolution
Air pollution
Air pollution
Oxidative stress
Toxicity
Abstract:
Air pollution remains the major environmental cause of premature death globally, with long-term exposures to elevated concentrations of microscopic airborne particles and pollutant gases associated with both increased cardiovascular and respiratory hospital admissions and deaths. These adverse effects of living for long periods in areas of elevated pollutant concentrations are much greater than the those associated with short-term exposures, such as those associated with an air pollution episode, which has led to the hypothesis that air pollution not only aggravates disease symptoms in vulnerable groups, such as individuals with pre-existing chronic disease but may also contribute to their development. Consistent with this view, air pollution exposures have been shown to be associated with early signs of cardiovascular and respiratory disease, such as hypertension, high cholesterol, inflammation, and poor lung function in otherwise healthy individuals. This has significant policy implications as it implies reducing air pollution exposures in early to midlife has the potential to provide benefits far into the future, reducing age-related disease and their associated health costs. This expands our understanding of the vulnerability of the population to air pollution, emphasizing how important early life exposures are to health in later life. There are however considerable gaps in our knowledge of how air pollution exposures in childhood to mid-life can promote these adverse responses. Part of the problem here is that our understanding of how air pollution causes harm to the human body is largely based on studies that examine short-term responses to pollutants. We know very well that air pollution causes damaging oxidation reactions in the body and elicits inflammation, both in the lung and circulation, but what is less clear is how these responses relate to the effects of long-term, low-level cumulative exposures. Compounding this is the absence of clear biological indicators of long term exposures. Recently it has become apparent that under a range of environmental stresses, DNA can undergo structural changes modifying the way in which genes are switched on and off. While some of these changes occur very rapidly, before resolving, others appear stable over time and potentially even inheritable across generations. As these alterations can occur in genes with functional roles in the regulation of inflammation, or the detoxification of particle components, identifying these DNA changes has the potential to provide insights into the underlying mechanisms contributing to the long-term effects of air pollution. This is the central aim of this study; to identify DNA modifications in genes in both children and adults that are associated with air pollution exposures, are stable across time and can be related to the early life risk factors for cardiovascular disease. To achieve this, we will estimate the exposures of children and adults in three large population cohorts using state of the art modeling that will allow us to consider the impacts of a broad range of chemical components within the air we breathe. This approach has the potential not only to improve our understanding of the components within the air pollution mix that increase our vulnerability to pollution but also to drill down into the underlying causal mechanisms. This will have significant policy impacts, both in terms of the development of targeted pollutant mitigation actions and communication strategies explaining the risks of air pollution to the 'healthy' general public before clinical symptoms become apparent in later life.
Period of Award:
1 Jul 2020 - 31 Oct 2023
Value:
£1,165,125 Lead Split Award
Authorised funds only
NERC Reference:
NE/T001895/2
Grant Stage:
Completed
Scheme:
Directed (RP) - NR1
Grant Status:
Closed
Programme:
Clean Air

This grant award has a total value of £1,165,125  

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FDAB - Financial Details (Award breakdown by headings)

DI - Other CostsIndirect - Indirect CostsDA - InvestigatorsDI - StaffDA - Estate CostsDA - Other Directly AllocatedDI - T&S
£442,390£272,967£25,949£321,229£85,751£1,443£15,396

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