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

GSTDTAP

项目编号	NE/T001895/1
	Component-Specific Air pollutant Drivers of Disease Risk in Early to Midlife: a pathway approach. (DREaM)
	Ian Stanley Mudway
主持机构	King's College London
项目开始年	2019
	2019-02-13
项目结束日期	2022-02-12
资助机构	UK-NERC
项目类别	Research Grant
项目经费	1285073(GBP)
国家	英国
英文摘要	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.
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文献类型	项目
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/87519
专题	环境与发展全球科技态势
推荐引用方式 GB/T 7714	Ian Stanley Mudway.Component-Specific Air pollutant Drivers of Disease Risk in Early to Midlife: a pathway approach. (DREaM).2019.