Theme 1: Epidemiological assessment of low level environmental - - PowerPoint PPT Presentation

12/11/2014

Theme 1: Epidemiological assessment

• f low level environmental exposures

Lead: Anna Hansell (Imperial); Deputy lead: Tony Fletcher (PHE)

Presenter: Tony Fletcher (PHE)

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

• rganic 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 13th 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

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Theme 2 – Modes and Mechanisms of Toxicity

Tim Gant: PHE David Phillips: KCL

Overall Theme Aim

Chemical exposures are an unavoidable component of many aspects

• f 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

• f the epigenome in target cell types.

Milestones

• By the end of year 1 the methodology will have been set up for the analysis
• f 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

• n 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,

• rganic 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

• ccur 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).

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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)

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

Theme 3

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

Project 2

Electromagnetic fields

The issue: 7 billion users of mobile devices including children, adults and emergency services personnel, yet IARC classified RF- EMF as ‘possibly carcinogenic to humans’. Evidence to date is inconclusive mainly due to limitations of retrospective study designs The approach:To enhance 3 ongoing prospective cohort studies with in-depth RF-EMF exposure assessment in children (SCAMP), adults (COSMOS), and the Police Force (AIRWAVE) Progress: AIRWAVE - publication of cohort profile SCAMP – ethics approval for main cohort obtained, pilot study and focus groups completed, successful media launch achieved, cohort recruitment started, data collection in schools started

Project 3

UV radiation and Vitamin D

The issue: How is the skin cancer risk associated with UV exposure balanced with the benefit of Vitamin D sufficiency? The approach: Investigation of immune system effects in blood and skin of solar simulated UVR and dietary supplementation of Vitamin D; investigation of cellular damage in human melanoctyes by UVR and UVR plus sun screen Progress: Ethical application for human study in progress UV/TiO2 effects on heme oxygenase gene expression (marker of oxidative stress), suggestive of interaction leading to higher levels of oxidative stress

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Theme 4 – Health effects of noise and air pollution including nanoparticles

Heather Walton, KCL Rachel Smith, PHE

Project 1 – Optimising assessment of health impacts of air pollution

• Lead: Heather Walton (King’s); Deputy lead Klea Katsouyanni (King’s)
• Assessing health impacts of air pollution in the best way is important for PHE for
• (i) advising Defra on assessing health benefits of air pollution reduction policies

to so that policies with the greatest benefit to health are chosen

• (ii) Determining public health priorities at local level e.g. Through the public

health outcome indicator for fine particles

• (iii) Communication with the public

Project 2 – Neurocognitive and behavioural impacts of traffic derived pollutants in children

Lead: Ian Mudway (King’s); Deputy lead Frank Kelly (King’s)

• Starting 2015

Project 1

Collate CRFs COMEAP/HRAPIE NIHR funded systematic review Match scale of modelling Develop methodology e.g. Thresholds vs cut-offs

2 4 6 8 10

City of… Bexley Camden Enfield Hamm… Havering Islington Lambeth Newham South… Waltha… England

Fracti tion n of mortalit lity y attributa ibutabl ble to particul culate te air pollutio tion n (%)

Area Name 3.01 - Fraction of mortality attributable to particulate air pollution

Calculations in London Ozone and health quantification and climate change

Nanoparticles: Exposure and Effects

Theme 4 Project 3: Nanoparticle Exposure Assessment PHE: Rachel Smith, Alison Buckley

• Review of available nano-products
• Characterise materials and exposures

Nanoparticles: Exposure and Effects

Theme 4 Project 4: Health Effects of Nanoparticles Imperial College: Terry Tetley, Andrew Thorley, Liz Smith

• Established co-culture of human lung alveolar cells – eg microvascular cells (blood) with

mixed epithelial type 1 and type 2 cells

• Exposed human lung microvascular cells to panel of MWCNTs, 700nm x 15nm – as received

(AR; ZP = -10), acid oxidised (AO), and functionalised with polyethylene glycol [P(PEG); ZP = -5], N-methyl 4-vinylpyridine [P(M4-VP); ZP = +10], methacrylic acid [P(MAA); ZP = -15]. Bioreactivity of these MCNTs differs for cell death, cytokine production, thrombotic factors (all shown) as well as oxidative stress, altered transendothelial resistance and macropahge migration (not shown).

PHE: Rachel Smith, Martin Leonard, Chang Guo

• Cells include upper airway co-culture (Theme 2)
• Use of ALI system for direct aerosol deposition