Using metabolomics to investigate the metabolic signatures and associated pathways linked to short-term exposure to air pollutants
Lead Research Organisation:
King's College London
Department Name: Analytical & Environmental Sciences
Abstract
Human exposure to air pollution contributes to approximately 7 million deaths per year worldwide and owing to the high prevalence of heart disease across the globe, the majority of deaths are attributed to cardiovascular disease (CVD). The epidemiological evidence for independent associations between exposure to poor air quality and CVD mortality is compelling. With respect to illness, heart disease, furring of the arteries (atherosclerosis), heart failure, abnormal heart rhythms and stroke have all been associated with air pollution. For long-term exposure to particulate matter (PM), associated detrimental effects have been shown to persist at concentrations below current annual national standards, whilst reductions in ambient PM (particularly, PM less than 2.5 microns in diameter, PM2.5) have been associated with a slower progression of atherosclerosis.
To better understand whether the associations between air pollution and risk of CVD reported in such studies are causal, requires a more comprehensive characterisation of the underlying biochemical pathways and accompanying mechanisms. In particular, if we can identify intermediate steps that lie on the casual pathway(s) linking air pollution to CVD, this could guide appropriate policy and action, including technical solutions and behavioural change, to mitigate the effects of air pollution on health.
In this proposal, we aim to use emerging 'whole systems' approaches to study the mechanistic pathways linking ambient air pollution exposure to CVD. These approaches involve metabolic phenotyping technologies (metabolomics) that have emerged as a powerful tool to capture information on a range of toxicological and disease processes. Such metabolic profiling captures a wide range of end products of human metabolism and detects signals from a variety of sources including genetic, dietary, other lifestyle, gut microbial and environmental influences such as air pollutants.
Specifically, we will use the concept of the metabolome-wide association study, pioneered by our Centre, to investigate the metabolic fingerprint, which will enable us to discover novel blood-based markers of air pollution exposure (PM2.5 and nitrogen dioxide). Establishing such bio-markers is a key initial step in understanding which biochemical pathways are influenced by air pollution. The results of this research should better our understanding of the mode of action and toxic properties of particulates and gaseous pollutants. Such advances are essential to design and implement better air pollution abatement and control policies, and hence reduce the high burden of air pollution related illness and mortality.
To better understand whether the associations between air pollution and risk of CVD reported in such studies are causal, requires a more comprehensive characterisation of the underlying biochemical pathways and accompanying mechanisms. In particular, if we can identify intermediate steps that lie on the casual pathway(s) linking air pollution to CVD, this could guide appropriate policy and action, including technical solutions and behavioural change, to mitigate the effects of air pollution on health.
In this proposal, we aim to use emerging 'whole systems' approaches to study the mechanistic pathways linking ambient air pollution exposure to CVD. These approaches involve metabolic phenotyping technologies (metabolomics) that have emerged as a powerful tool to capture information on a range of toxicological and disease processes. Such metabolic profiling captures a wide range of end products of human metabolism and detects signals from a variety of sources including genetic, dietary, other lifestyle, gut microbial and environmental influences such as air pollutants.
Specifically, we will use the concept of the metabolome-wide association study, pioneered by our Centre, to investigate the metabolic fingerprint, which will enable us to discover novel blood-based markers of air pollution exposure (PM2.5 and nitrogen dioxide). Establishing such bio-markers is a key initial step in understanding which biochemical pathways are influenced by air pollution. The results of this research should better our understanding of the mode of action and toxic properties of particulates and gaseous pollutants. Such advances are essential to design and implement better air pollution abatement and control policies, and hence reduce the high burden of air pollution related illness and mortality.
Technical Summary
Air pollution contributes to 7 million deaths per year worldwide; the vast majority of those deaths are attributed to cardiovascular disease (CVD). The objective of this proposal is to examine the initial steps that lie on the causal pathway(s) linking exposure to air pollution and disease risk using multivariate metabolic phenotyping technologies (metabolomics) that have emerged as a powerful new method to capture biomarker information on a range of toxicological and disease processes.
Our proposal takes advantage of existing data and samples from human chamber studies with three exposure scenarios (diesel, biodiesel, wood smoke), a 'real world' study of urban and peri-urban residents in Beijing with extensive personal exposure monitoring during winter and summer (AIRLESS and Oxford Street II with its extensive monitoring of air pollutants and already available metabolic data.
We will use the metabolome-wide association study paradigm to investigate the metabolic fingerprint associated with (a) short- and long-term exposures to air pollutants and whether these are these replicated across different exposure scenarios. We will then apply chemometric, statistical and analytical chemistry approaches to structurally detect the significant metabolic features, followed by bioinformatics, statistical methods and analysis to identify the underlying metabolic pathways involved in different exposures and exposure scenarios, as well as exposure-specific pathways. The resulting data are expected to provide novel insights into the mechanisms underlying the adverse health effects of air pollution and provide a firm foundation for future work which addresses the possible links between these perturbations and early disease events.
Our proposal takes advantage of existing data and samples from human chamber studies with three exposure scenarios (diesel, biodiesel, wood smoke), a 'real world' study of urban and peri-urban residents in Beijing with extensive personal exposure monitoring during winter and summer (AIRLESS and Oxford Street II with its extensive monitoring of air pollutants and already available metabolic data.
We will use the metabolome-wide association study paradigm to investigate the metabolic fingerprint associated with (a) short- and long-term exposures to air pollutants and whether these are these replicated across different exposure scenarios. We will then apply chemometric, statistical and analytical chemistry approaches to structurally detect the significant metabolic features, followed by bioinformatics, statistical methods and analysis to identify the underlying metabolic pathways involved in different exposures and exposure scenarios, as well as exposure-specific pathways. The resulting data are expected to provide novel insights into the mechanisms underlying the adverse health effects of air pollution and provide a firm foundation for future work which addresses the possible links between these perturbations and early disease events.
Planned Impact
This work will have academic, economic and societal impact, effectively enhancing the knowledge economy across disciplines (toxicology, biochemistry [metabolomics], epidemiology, biostatistics, and bioinformatics). Our applied scientific research will be widely disseminated and applicable internationally and as such, its generation will enhance the status of UK science.
The project has considerable potential to deliver strategic impact at the public health level in that the knowledge gained has potential to improve our understanding of a fundamental environmental influence (i.e the air we breathe) on health. The results of this research could help identify the most toxic forms of pollution (i.e. diesel, woodsmoke, brake wear PM) and may guide environmental strategies to improve air quality and potentially lead to improved public health. Together these should result in reductions in health-care costs and lead to significant health gains and a better quality of life.
In addition, this work has potential to contribute to policy development. Advances into understanding the mode of action and toxic properties of particulates and gaseous pollutants will empower the design and help implement effective air pollution abatement and control policies and measures, including policy, technical and behavioural change, thereby reducing the high burden of air pollution related morbidity and mortality. With the advancement of evidence-based policy, UK led research of this nature can become a test-bed for cities around the world, therefore generating international interest and leadership.
The project has considerable potential to deliver strategic impact at the public health level in that the knowledge gained has potential to improve our understanding of a fundamental environmental influence (i.e the air we breathe) on health. The results of this research could help identify the most toxic forms of pollution (i.e. diesel, woodsmoke, brake wear PM) and may guide environmental strategies to improve air quality and potentially lead to improved public health. Together these should result in reductions in health-care costs and lead to significant health gains and a better quality of life.
In addition, this work has potential to contribute to policy development. Advances into understanding the mode of action and toxic properties of particulates and gaseous pollutants will empower the design and help implement effective air pollution abatement and control policies and measures, including policy, technical and behavioural change, thereby reducing the high burden of air pollution related morbidity and mortality. With the advancement of evidence-based policy, UK led research of this nature can become a test-bed for cities around the world, therefore generating international interest and leadership.
Organisations
Publications
Abbasi S
(2020)
Elemental and magnetic analyses, source identification, and oxidative potential of airborne, passive, and street dust particles in Asaluyeh County, Iran.
in The Science of the total environment
Carter E
(2019)
Household Transitions to Clean Energy in a Multi-Provincial Cohort Study in China.
in Nature sustainability
Chatzidiakou L
(2020)
Using low-cost sensor technologies and advanced computational methods to improve dose estimations in health panel studies: results of the AIRLESS project.
in Journal of exposure science & environmental epidemiology
Chatzidiakou L
(2019)
Characterising low-cost sensors in highly portable platforms to quantify personal exposure in diverse environments
in Atmospheric Measurement Techniques
Chng KR
(2020)
Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment.
in Nature medicine
Chung Y
(2019)
Our change of Co-Editor-in-Chief and the journal's prospects
in Air Quality, Atmosphere & Health
Evangelopoulos D
(2020)
The role of burden of disease assessment in tracking progress towards achieving WHO global air quality guidelines.
in International journal of public health
Evangelopoulos D
(2021)
Personal exposure to air pollution and respiratory health of COPD patients in London.
in The European respiratory journal
Friberg M
(2023)
Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response.
in Particle and fibre toxicology
Han Y
(2020)
Effects of AIR pollution on cardiopuLmonary disEaSe in urban and peri-urban reSidents in Beijing: protocol for the AIRLESS study
in Atmospheric Chemistry and Physics
Hoffmann B
(2020)
Air pollution and health: recent advances in air pollution epidemiology to inform the European Green Deal: a joint workshop report of ERS, WHO, ISEE and HEI.
in The European respiratory journal
Karima Zitouni
(2019)
Arteriosclerosis, Thrombosis and Vascular Biology
in Cross-sectional analysis of the relationship of 8-OHdG and vascular compliance in patients with type 2 diabetes at high risk of cardio-renal disease
Kelly F
(2020)
Toxicity of airborne particles-established evidence, knowledge gaps and emerging areas of importance
in Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
Kelly F
(2020)
Oxidative Stress
Kelly FJ
(2021)
Air Pollution and Asthma: Critical Targets for Effective Action.
in Pulmonary therapy
Kelly FJ
(2020)
Our change of Co-Editor-in-Chief and why the journal's future is bright.
in Air quality, atmosphere, & health
Kelly FJ
(2020)
Global nature of airborne particle toxicity and health effects: a focus on megacities, wildfires, dust storms and residential biomass burning.
in Toxicology research
Kelly FJ
(2019)
Urban air quality and health: two steps forward, one step back.
in The European respiratory journal
Koelmans A
(2019)
A scientific perspective on microplastics in nature and society
Lee M
(2021)
Determinants of personal exposure to PM2.5 and black carbon in Chinese adults: A repeated-measures study in villages using solid fuel energy
in Environment International
Levermore J
(2020)
Detection of Microplastics in Ambient Particulate Matter Using Raman Spectral Imaging and Chemometric Analysis
in Analytical Chemistry
Liang L
(2019)
Associations between daily air quality and hospitalisations for acute exacerbation of chronic obstructive pulmonary disease in Beijing, 2013-17: an ecological analysis.
in The Lancet. Planetary health
Meng Y
(2020)
Advances and challenges of microplastic pollution in freshwater ecosystems: A UK perspective
in Environmental Pollution
Mudway I
(2020)
Oxidative stress in air pollution research
in Free Radical Biology and Medicine
Mudway IS
(2020)
Air pollution: Consequences for cellular redox signaling, antioxidant defenses and disease.
in Free radical biology & medicine
Newbury JB
(2019)
Association of Air Pollution Exposure With Psychotic Experiences During Adolescence.
in JAMA psychiatry
Preston GW
(2020)
Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study.
in Chemosphere
Rachel B Smith
(2020)
Environment International
in Impacts of air pollution and noise on risk of preterm birth and stillbirth in London
Rivas I
(2019)
Indoor Air Pollution
Rivas I
(2020)
Source apportionment of particle number size distribution in urban background and traffic stations in four European cities.
in Environment international
Robert S
(2019)
Psychiatry Research
in Exploration of NO2 and PM2.5 air pollution and mental health problems using high-resoultion data in London-based children from the UK longitudinal cohort study
Smith James
(2020)
Environmental International
in PM2.5 on the London Underground
Smith JD
(2020)
PM2.5 on the London Underground.
in Environment international
Smith R
(2020)
Impacts of air pollution and noise on risk of preterm birth and stillbirth in London
in Environment International
Steyn M
(2019)
Sex Differences in Glutathione Peroxidase Activity and Central Obesity in Patients with Type 2 Diabetes at High Risk of Cardio-Renal Disease.
in Antioxidants (Basel, Switzerland)
Steyn Mia
(2020)
Antioxidants
in Sex Differences in Glutathione Peroxidase Activity and Central Obesity in Patients with Type 2 Diabetes at High Risk of Cardio-Renal Disease
Trechera P
(2021)
Comprehensive evaluation of potential coal mine dust emissions in an open-pit coal mine in Northwest China
in International Journal of Coal Geology
Trechera P
(2020)
Mineralogy, geochemistry and toxicity of size-segregated respirable deposited dust in underground coal mines.
in Journal of hazardous materials
Wright S
(2019)
Raman Spectral Imaging for the Detection of Inhalable Microplastics in Ambient Particulate Matter Samples
in Environmental Science & Technology
Wright SL
(2020)
Atmospheric microplastic deposition in an urban environment and an evaluation of transport.
in Environment international
Yan L
(2019)
Study protocol: The INTERMAP China Prospective (ICP) study
in Wellcome Open Research
Zazouli MA
(2021)
Physico-chemical properties and reactive oxygen species generation by respirable coal dust: Implication for human health risk assessment.
in Journal of hazardous materials
Zitouni K
(2020)
Derepression of glomerular filtration, renal blood flow and antioxidant defence in patients with type 2 diabetes at high-risk of cardiorenal disease.
in Free radical biology & medicine
Related Projects
| Project Reference | Relationship | Related To | Start | End | Award Value |
|---|---|---|---|---|---|
| MR/S020810/1 | 31/03/2019 | 30/03/2020 | £684,265 | ||
| MR/S020810/2 | Transfer | MR/S020810/1 | 31/03/2020 | 30/03/2023 | £615,557 |