Hazard Identification Platform to Define the Health Impacts associated with Indoor and Outdoor Air Pollutant Exposures, through the Application of Mechanistic Toxicity

Over the last decade our understanding of the impact of air pollution on both short- and long-term population health has advanced considerably, with increased appreciation of impacts below current regulatory limits and beyond the cardiopulmonary systems, particularly upon the brain in relation to poor mental health and dementia risk. However, there are still major gaps in our understanding of the most harmful components within the air we breathe and the mechanisms by which they induce adverse effects.

The challenges associated with outdoor exposures to air pollution are further magnified when a more holistic view of individual exposures of increasing chemical complexity, including indoor air, are considered in relation to an adverse health outcome. This requires a multidisciplinary approach in which we will apply toxicological principles across a range of in vitro and animal model systems to human subject exposures, to evaluate the mechanisms by which source-specific aerosols (reflecting commonly emitted pollutants within indoor and outdoor air) induce negative impacts on brain function. In addition to acute neuronal injury, adverse pathways linked with severe neurological effects of long-term exposures include induction of neuro inflammation and oxidative stress.

The aim of this project is to provide a platform for the relative ranking of the hazard of specific aerosols across the indoor-outdoor continuum, and the identification of the causal chemical components driving these adverse health effects. Ultimately these data will allow greater refinement in policy actions aimed at mitigating against the harmful effects of air pollution, by identifying priority sources and components for more targeted actions to protect the health of vulnerable groups and to prevent avoidable chronic disease in the future.

A world-leading interdisciplinary and self-sustaining research consortium will develop an Air Pollution Hazard Identification Platform. This facility will be centred at the University of Manchester and will support deployable aerosol generating infrastructure for in vitro and in vivo toxicological work programmes between partners and longer-term to the wider UK research community. Our aims are:

1. Equipping the UK to proactively tackle air quality challenges, related to changing emissions
2. To investigate impacts on groups of people most at risk, specifically to promote our understanding of the toxicology and health impacts of future exposure and emission scenarios.

Integration of in vitro, in vivo (animal-based studies) and human experimental exposures will deliver translational toxicological findings directly relevant to critical policy questions across the indoor to outdoor exposure continuum. Establishment of the platform will enable us to deliver the following outputs:

i)    To provide a ranking of the relative hazard of specific sources against adverse responses,

ii)   To identify specific causal chemicals, or chemical classes linked to disease aetiology, progression, and exacerbation; importantly benchmarked against human in vivo responses.

The application of in vitro cell systems and genetically modified animal models, adds research power to enhance our understanding of underlying toxicology mechanisms driving adverse effects, including in the most susceptible members of society.

PI: Dr Ian Mudway