Theme 1: Epidemiological assessment of low level environmental exposures Lead: Anna Hansell (Imperial); Deputy lead: Tony Fletcher (PHE) Presenter: Tony Fletcher (PHE) 12/11/2014
Theme 1 (Epidemiology) Objective: To use epidemiology and surveillance to quantify associations between disease and exposure to environmental hazards. Projects: A. Science-based policy for assessing suspected environmentally caused disease clusters B. Two contrasting exposures highlighted: Carbon monoxide (significant population health burden) Bio-aerosols (absence of data on population impacts) C. Other exposures of interest: water, soil and food contaminants (including arsenic and heavy metals), exposure to persistent organic pollutants (including perfluorinated substances)
Project 1 - Carbon monoxide (Rebecca Ghosh/Giovanni Leonardi) Extent of low-level exposure to CO to a much larger proportion of the English population than previously thought, but burden still uncertain; project comprises several complementary studies: a) Hospital admissions to investigate trends in CO poisoning (SAHSU data) – Paper submitted on schedule : Analysis of hospital admissions due to Carbon Monoxide poisoning in England, between 2001 and 2010. Rebecca E Ghosh, Rebecca Close, Helen Crabbe, Lucy McCann, Kevin Garwood, Anna L Hansell, Giovanni Leonardi. Journal of Public Health, July 2014 b) Estimated CO-caused attendances to A&E Depts – Paper by September 2015 c) Planned integrated assessment of linked health data across (A&E, admissions and mortality datasets) and exposure and exposure markers for more complete picture of the burden of CO poisoning in England – under development
Project 2 – Bioaerosols from waste composting (Anna Hansell/Tim Gant) Particular concern for DEFRA and EA, lacking evidence base for regulating composting on health grounds. Work plan: systematic reviews, exposure assessment, planning epidemiology study. a) Bioaerosols review paper: submitted Sept 2014 on schedule : Clare Pearson, et al Journal of Toxicology and Environmental Health Part B b) Report to Defra of pilot epidemiological study, Oct 13 th 2014 . c) Poster at the ISEE Barcelona conference Oct 20-21 d) Paper on epidemiological pilot study to journal November 2014 e) Scoping meetings with EA, Defra, PHE, HSL Oct-Dec 2014 f) Further systematic review on bioaerosols on health, Mar 2015 g) Design a national epid study using SAHSU data: asthma and respiratory hospital admissions and low birth weight. 2015 h) A biocomposting emissions modelling paper, March 2016
Project 3 Disease Cluster Policy (Tony Fletcher/Anna Hansell) Two linked activities, in parallel initially, then integrated: Cluster Guidelines a) Develop draft - done on schedule b) consult within PHE (CKO, PHECs, FES) active c) Poster at ISEE Barcelona conference Oct 20-21 d) consult more widely early 2015 e) prepare guidelines Sept 2015 f) prepare scientific paper Dec 2015 RIF Rapid Inquiry Facility development a) reprogramming – underway b) field testing/ user consultations 2015 c) RIF live March 2016 d) prepare Guidelines v2, including access to RIF early 2016
Theme 2 – Modes and Mechanisms of Toxicity Tim Gant: PHE David Phillips: KCL 12/11/2014
Overall Theme Aim Chemical exposures are an unavoidable component of many aspects of modern life. Some exposures are direct and intentional, for example from cosmetics and drugs, and some indirect and unintentional, such as from agricultural chemicals or products of combustion. This theme focuses on using high throughput methods of analysis (sequencing, genomics, mass spectrometry and nuclear magnetic resonance), that are all strengths of the partners, to identify biomarkers and improve mechanistic understanding of environmental hazards being assessed at the population level in the other 3 themes.
T2/P1 - Epigenetic effects of chemical exposure Hypothesis: that environmental chemical exposures lead to specific alteration of the epigenome in target cell types. Milestones • By the end of year 1 the methodology will have been set up for the analysis of methylation marks on the genome using an antibody precipitation and high throughput sequencing analysis – This has been achieved and data analysis is ongoing. • By the end of the second year a hazard characterisation paper will have been delivered that analyses the effects of several environmental chemicals on epigenetic methylation patterns in the genome using the method outlined above – Substantial amounts of work complete; should be achieved. • A further study that is dependent on additional funding from other sources is the analysis of chemicals in human seminal fluid and correlation of these exposures with changes in the miRNA expression in the sperm – Means to facilitate this are being explored. Our primary clinical collaborator has moved to the middle east so we are exploring contacts with the John Radcliffe Hospital and Sheffield University.
T2/P2 - Foetal Exposures Aim: An analysis of foetal blood spots will be undertaken for metals, organic chemicals and if feasible carboxyhemoglobin. Milestones • This is a one year project with an aim to analyse 1000 blood spots. This project is short staffed due to PHE restrictions on hiring including using NIHR monies. This may cause a delay in this project. Some Additional funding has been obtained from PHE
T2/P3 – Toxicokinetics Aim: To develop toxicokinetic models that permit the evaluation of internal exposure at the target site from measures taken in accessible body fluids such as urine and blood. Milestones ; • By month 18 the models will have been established – should be met • From month 18 models will be tested and coded into a computer program – should be met We have an new PhD student working on this project from other funding (PHE) that will contribute to the NIHR project: Alex Cooper registered at Imperial.
T2/P4 - Mechanisms of chemical effects modifying response to aeroallergens Hypothesis: Pollutant chemicals can affect the response to aeroallergens by alteration of type or severity of molecular events that occur after allergenic exposure. Milestones • Within the first 6 months cultures of bronchial epithelial cells from both normal and asthma patients will be cultured - this is done and some data has been presented as a poster • By12 months optimisation of epithelial and dendritic cell co-cultures will be carried to allow both acute and chronic exposure regimes – this will be met • Within 24 months optimised co-culture systems will be exposed to common allergenic material – this will be met A new PhD student Kirsty Meldrum (PHE funded) will also contribute to this project
T2/P5 - Bioaerosols, aeroallergens and complex mixtures Aim: Development of molecular analytical methods for fungal spores to better assess exposure. • It is envisaged that the quantitative methodological development will be complete by the end of year one – will not be met due to PHE hiring restrictions.
T2/P6 – Genotoxicity of air pollutants Aim: to develop and refine sensitive analytical methods to measure diesel- specific nitro-PAHs in urban air particulate matter and examine the effect of particle-bound polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs on pulmonary inflammation and DNA alteration, alone and in combination with aeroallergens. Milestones • We have recruited a post-doctoral scientist, Dr Ian Jarvis, who will join King’s College in January 2015, to work on cellular responses to carcinogenic air pollutants and complex mixtures thereof. We have also initiated the incorporation of protocols for co-culturing cells, developed at PHE, that will enable us to investigate the effects of inflammatory and immune responses on carcinogen activation.
T2/P7 - Approaches to analysis of the serum and urinary metabolome Aim: Development of metabolome methods for application in epidemiology Milestones • A series of technical and methodological papers providing the basis for the analysis of metabolomic data both within and between platforms (NMR, MS) as part of exploration of the exposome in rich epidemiological datasets (Year 2).
Theme 3 – Health impact of low dose non-ionising and ionising radiation Leads: Simon Bouffler (PHE) and Mireille Toledano (Imperial) Presenter: Dr Simon Bouffler (PHE) 12/11/2014
Theme 3 Health impact of low dose non- ionising and ionising radiation Aim: To quantify the health risks and benefits associated with exposure to low level non-ionising and ionising radiation, including the effects of light, UV and radiofrequency exposures
Project 1 Novel human cell model of atherogenesis The issue : Epidemiological studies are beginning to suggest low levels of IR exposure are associated with elevated circulatory disease risk The approach : Establish a robust human cell model of atherogenesis and investigate effects of IR Progress : Model established High dose effect on monocyte adhesion established Epigenetic basis under investigation First publication
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