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

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.

The overall aim of this study, in terms of impacts beyond its academic objectives, is to provide an evidential base that supports air pollution mitigation to improve public health and reduce the personal and societal costs associated with NCD.

This project has many potential beneficiaries and its outputs are likely to act across a range of scales from local to international: (1) the most immediate impact will be to the public, particularly to those within the CHILL study areas in London and Luton, and the police within the occupational AIRWAVE cohort, who will kept informed of the research findings arising from this work throughout the course of the study. The study will highlight the early origins of disease and the role that air pollution can play in these processes by impairing lung growth or promoting increases in known risk factor for the development of CVD.(2) The second major group will be policy makers, who will need to respond to these findings to develop new abatement strategies, or mechanisms to reduce exposures in vulnerable groups. The increased focus on PM components, as opposed to simply particle mass has the potential to identify particularly harmful sources, which may aid in the development of more tailored solutions to the current challenges of urban air quality. (3) Relevant professional bodies working in health care (NHS), occupational health, transport or involved in the development of disease prevention strategies at local and national government level. (4) Third sector organisations, especially those involved in health advocacy and efforts to improve urban environments. (5) Industry, especially firms involved in the development of low cost air quality sensors, portable health technologies and air filtration systems for work places in schools. The findings may also influence major car manufacturers, to accelerate the development of low pollution vehicles. (6) Academic and research communities (as described in the academic beneficiaries section).

Dissemination to these wider stakeholder groups will be coordinated via the MRC-PHE Centre for Environment & Health's Community Advisory Board (Chaired by the study PI), comprising NGOs, politicians, patient groups, public health professional and representatives from press and industry. All members of the study team will be encouraged to present to this forum, with a focus on the development of ethical amendments, participant engagement in the CHILL and AIRWAVE cohorts, and effective communication of study findings. Because of the latency period between early to midlife exposures and the emergence of NCDs later in life there are significant challenges in communicating health risks, particularly during middle age, and we will work with closely with PPI/E professionals within our organisations to ensure we address this challenge. The vulnerable, are not only those with pre-existing disease, but those on the pathway to sub-optimal health in later life. More detail on our strategies to ensure effective engagement with the stakeholder communities outline above is included in our Pathways to Impact statement.