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Organization
AIRPOLIFE had a successful 2-day kick off meeting in Copenhagen 22-23.4.2004. All investigators (42) and the entire International Advisory Board (IAB, Paul Borm , Gerard Hoek , Paolo Vineis were present throughout. At the kick-off meeting the entire project and all Work Packages (WPs) were presented and discussed with the IAB and among all investigators. Two WPs (3B and 3C ) were subject to criticism and has been altered in accordance with and support from the IAB as outlined below in the WP status section.
The steering committee has had three coordination meetings in 2004 and discussed revision and progress in the WPs. The PI and partner committee has met twice in 2004. The scientific forums have served as discussion forums and researcher educations with frequent meetings with discussion of WP details, progress and results as well as related projects and relevant literature.
There has been no change in partners or budgets in 2004, except that a few WPs proceed a little slower than planned and some of the budget will be transferred to 2005.
Web page
AIRPOLIFE has opened a web page (www.airpolife.dk), so far presenting the entire project in English. The web page will be expanded with a Danish section describing the project, results and disseminating result and knowledge on health effects in lay terms based on all sources, including the international literature. This activity is supported by an additional grant from the Research Councils.
Progress, revision and status of work packages
Detailed descriptions of each work package with time schedules have been developed as a dynamic tool to monitor progression. A summary of each is presented below. Full descriptions are available.
WP1AA. Physical-chemical characterization of particulate air pollution.
PI: Marianne GlasiusNERI AE , key researchers: Matthias KetzelNERI AE , Peter Wåhlin NERI AE ,
Finn PalmgrenNERI AE, Jacob G. MønsterNERI AE (new PhD student) Keld Alstrup JensenNIOH
Aim: To provide detailed physico-chemical characterization particulate air-pollution from specific sources and input on particle composition and source contributions for epidemiological and toxicological studies on adverse health effects from particulate air-pollution.
External Partners: University of Lund (EC/OC measurements on filters); University of Copenhagen (XRD and DMPS measurements); Aarhus University (Electron Microprobe Analysis); University of Michigan (HAADF STEM); EC Joint Research Centre, Ispra, Italy (PAH and nitro-PAH analysis).
Status of the project March 2005.
Metal speciation: Two measurement campaigns are planned in 2005. They will focus on brake wear particles emissions, indoor/outdoor and characterization.
EC/OC: Continuous measurements with carbon monitors (ACPM). New equipment for soot measurements has been acquired. It is now being tested and installed. Samples for PAH and nitro-PAH analysis have been collected and PAH are now being analysed. Development of analysis method for nitro-PAH is performed in 2005. Thermodenuder measurements of non-volatile particles (10-700 nm) have been performed. An indoor-outdoor study of PM2.5 and PAHs in shops along trafficked streets is conducted in connection with one of the metal speciation field campaigns.
In-vitro bioassays: Activities planned for 2005 are collection and analysis of samples in relation to the brake wear study.
WP1ABExposure assessment.
PI: Martin HvidbergNERIAE . key researchers: Martin Hvidberg NERIAE , Steen Solvang Jensen NERIAE, Ruwim Berkowicz NERIAE , Ole Hertel NERIAE, Mathias Ketzel NERIAE .
Aim: Development of model based assessment of historical air pollution exposure with high capacity and accuracy
Status:
1) "Data will be established to describe developments in road network, traffic density, building erection and domestic heating type over this period." Q1 2005 Status: 75% complete
2) "The AirGIS system will be further developed to take into account the historical changes in urban building structure and propagation in time using information from the building and housing registry." Expected delivery Q1 2005 Status: 90% complete.
"Historical records for regional and urban background levels of fine and ultrafine particle concentrations are derived together with historical records of emissions factors." Expected delivery Ultimo 2005 Status: 20% completed
4) "As the composition of the car fleet has changed considerably over time, data are collected in order to improve emission estimates". Expected delivery: Ultimo 2005 Status: 50% completed
5) "For the regional background, emission inventories are available back to the 1980’ties. Best available estimates are applied for going back to the 1960’ties. Expected to start in Q2 2005
6) "The AirGIS system will be optimised for exposure assessments in a human lifetime perspective."Expected delivery: Ultimo 2005 Status: 50% complete
7) "The spatial distribution of traffic on the urban street network is modelled roughly based on counts in specific locations and an assumption that streets of same class carry same load of traffic. These estimates will be sought verified and improved by use of remote sensing and spatial statistics."Expected delivery: Ultimo 2006 Status: 0% complete
8) "During model simplification, these assessments are compared to relatively simple assessment of local exposure based on one or more parameters as; distance to (busy) streets, address density within a buffer, traffic intensity within a buffer, number of (high trafficked) streets within a buffer, etc. all inferred from GIS operation." Work on this task is expected to start in Q3 2005.
WP1B Personal Monitoring
PI: Steffen Loft UCIPH key researchers: Elvira Vaclavik UCIPH (new PhD student), Peter Vinzents UCIPH, Peter MøllerUCIPH, Lars DragstedIFN , Herman Autrup AU, Jann MortensenRHPET, Ole HertelNERIAE, Marianne GlasiusNERIAE, Finn PalmgrenNERIAE , Peter Wåhlin NERIAE, Matthias KetzelNERIAE, Mette Sørensen UCIPH+ICE, Ole Raaschou-NielsenICE .
External Partners: Lars Gunnarsen, Danish Building and Urban Research; Erik Swietlicki and Jakob Löndahl, Lund University (LU), Lars Barregård, Gotenburg University, Alfred Bernard, Leuven University (all new collaborations).
Aim: To study associations between controlled exposure to ultrafine particles and biological effects.
Status: The interaction between exercise and exposure is studied in a 2x2 design on 30 healthy young non-smoking subjects in indoor exposure chambers with traffic generated air pollutants by use of a ventilator facing a busy street. The air pollutants are extensively monitored in the laboratory. Biological effects include alveolar integrity, mucociliar, lung and endothelial function, deposition of ultrafine particles, biomarkers of oxidative stress, DNA damage and gene regulatory responses. The exposure part of the study is half way. In collaboration with Gotenburg University responses of similar biomarker to wood smoke are studied in healthy subjects. Results from a parallel field study on biomarkers and traffic related air pollution in Benin is under publication.
Elderly subjects (40) will be studied in their home with and without filtering the indoor air for ultrafine particles. Supplementary financing (1.3 mill kr) for this part has been achieved from Velux.
WP2A Placenta particle transfer
PI Lisbeth E. Knudsen UCIPH , key researcher Tina Dam Mikkelsen UCIPH (applying for PhD study).
Aim: To study passage of ultrafine particles and function in human placenta
Status: The placental perfusion system is well established and functional. It will be validated by concurrent experiments in Kuopio and Copenhagen . Passage of ultrafine (initially gold, later genuine particles) through the placenta barriere will be detected by electron microscopy. DNA damage and gene activation induced ex vivo will be studied in maternal blood and cord blood by postlabelling, immunochemistry and in situ hybridisation.
WP2B Intrauterine exposure models
PI Håkan WallinAMI, key researcher post.doc. Karin Sørig HougårdAMI
Aim: Study effects of intrauterine exposure to air pollution particles on cognitive function.
Status: Exposure is planned ultimo 2005 with cognitive function assessment of offspring early 2006. Offspring will also be used for study of genotoxic endpoints and reproductive effects.
WP2C Target organ exposure in humans
Elvira Vaclacik (new PhD student)UCIPH, Peter VinzentzUCIPH , Lisbeth E. Knudsen UCIPH, Peter MøllerUCIPH Tina Dam Mikkelsen (expected PhD) studentUCIPH , Peter Wåhlin NERIAE, Marianne GlasiusNERIAE Lars DragstedIFN , Herman Autrup AU, Ole HertelNERIAE. Mette Sørensen UCIPH+ICE
Aim: Study associations between personal exposure to particles assessed by monitors and biomarker responses related to oxidative stress, DNA damage and gene regulation in target tissue (placenta and cord blood) in relation to planned caesarean section in 50 pregnant women.
Status: WP2C is closely linked to WP1B and WP2A and is planned for execution in 2006 – 2007.
WP2D Early exposure, birth weight, perinatal/infant mortality and early childhood airway disease
PI: Ole Raaschou-NielsenICE
Aims: To study the hypotheses that exposure to air pollution decreases birth weight, increase infant mortality and increases early childhood airway disease by means of the National Bith Cohort.
Status: The Danish Data Protection Agency has accepted the study. Children/mothers in the relevant area have been identified. Addresses have been traced and delivered to NERI. The development of the modeling system (NERI) is delayed, and therefore the original time schedule has been changed. Use of data from the National Birth Cohort was accepted by the steering committee by October 2004.
WP3A. Indoor air pollution and childhood asthma
PI: Ole Raaschou-NielsenICE
Aims: To investigate a possible influence of indoor air pollution on airway symptoms in 400 young children at risk of atopic disease.
Status: Due to delay in the development of the outdoor modeling system (NERI), we have decided to focus on the performed indoor measurements of air pollution. Data have been cleaned up and at present, we discuss 1) the need for calibration of PM data (due to different air flow), 2) systematic seasonal variation and implications for exposure assessment of each child, 3) inter-and intra individual variation in the repeated measurements (with and without calibration for flow and season). Airway episodes during the first 18 months of life has been registered and included in the measurement data file.
WP3B.Endotoxins and inflammatory potential of particles, and childhood asthma.
Due to uncertainty with respect to stability of particle material on earlier collected filters and a limited power pointed out by the IAB this WP has been replaced by WP3D (below).
WP3C Gene-environment interactions in childhood asthma
PIs: Herman Autrup and Steffen Loft (changed from Lisbeth Knudsen ).
Due to limitations in power pointed out by the IAB, focus has moved toward study of candidate genes involved in oxidative and metabolism in the National Birth Cohort. Details to be planned during 2005.
WP3D. Airway symptoms in children: inflammation genes, air pollution and ETS (replaces WP3B) PI Ole Raaschou-NielsenICE ,key researchers: Mette SørensenICE, Leila Allermann MøllerNIOH , Ulla Vogel NIOH , Steffen LoftUCIPH, Ole HertelNERIAE, Steen Solvang JensenNERIAE
Aims. To study associations between polymorphisms in inflammation genes and interactions with air pollution, in association with airway symptoms in 18 months old children based on the National Birth Cohort with 1000 cases and 1000 controls.
Status): The Danish Data Protection Agency and the Scientific Ethical Committee have accepted the study. A protocol was finished by October 2004. The Steering Committee of the Danish National Birth Cohort has accepted use of data and blood samples/DNA for the study. We have received an initial dataset on airway symptoms and work on identification of cases and selection of controls. The practical and economical conditions in association with blood samples and DNA cleaning are uncertain at present. Five candidate polymorphisms have been identified, assays have been designed and one assay has been set up.
WP4A. Cardiovascular disease models
PI: Peter Møller, key researchers: PhD student UCIPH+DP (not yet recruited due to possible cofinancing by research academy) , Christian Stevns-Hansen UCIPH+DP, Janne KjærgaardUCIPH, Steffen LoftUCIPH , Thomas Jonassen UCDP, Ole AmtorpUCDP, Håkan WallinNIOH
Aim: study cardiovascular effects of particles in animal models
Status: ApoE-/- and ApoE+/+mice have been studied with respect to inflammation, gene expression and oxidative stress in aorta and non-vascular target organs and endothelial function in aorta after i.p. and after ex vivo exposure to diesel particles with groundbreaking results. Reporter mice (NFkB) are being bred. The project will continue with exposures as planned when an optimal PhD candidate has been recruited.
WP4B Mortality, cancer and hospital admission in relation to air pollution – a cohort study
PI : Ole Raaschou-NielsenICE , key researchers: Martin HvidbergNERIAE, Steen Solvang JensenNERIAE, Ole HertelNERIAE, Anne TjønnelandICE, Mette SørensenICE
Aims: To study the hypotheses that exposure to ambient air pollution assessed by modelling at the address increases mortality, cancer and hospital admissions in the Diet Cancer and Health Cohort of 57.000 individuals recruited 1993-1997.
Status: The Danish Data Protection Agency has accepted the study. The Steering Commite of the DCH cohort has accepted the use of data. Historical addresses of DCH participants have been traced, cleaned, geocoded and delivered to NERI. NERI work on development of the modeling system. Allocation of traffic to the national Danish road system is the major challenge at present – in particular identification of the streets with the highest traffic density. Also a challenge is the historical dimension in estimation of traffic- and air pollution. We have started a pilot study to estimate the feasibility of “manual” tracing of traffic density for at all high-traffic Danish municipal streets, by contact to each municipality. A traffic model has provided traffic density for all streets in the Greater Copenhagen area (HT), and validation of these traffic estimates are under way. The model for estimation of background concentrations is nearly finished. It has to be validated against measurements. If the validation of traffic estimates in the HT area is successful, we will start the mortality study based on DCH participant who lived in the HT area at enrolment, and estimated air pollution at these addresses.
WP4C. Time-series analysis of CVD and respiratory disease
PI Steffen Loft. Key researchers Zorana AndersenUCIPH (PhD student), Finn PalmgrenNERIAE , , Peter Wåhlin NERIAE , Marianne GlasiusNERIAE , Thomas ScheikeUCIPH, Ole Raaschou-NielsenICE
Aim: To study associations between daily levels of air pollutants and health outcomes in Danish cities.
Status: Associations have been shown between daily levels of particles (PM10) and traffic related gases and all cardiovascular and lung disease admissions during 1999-2000 in Copenhagen and daily airway symptoms among 411 children with high risk of atopic disease during their first 18 months of life. Study periods will be updated including 2004 and air pollutants expanded to ultrafine particles, elemental composition of particles and source allocation.
WP4D. Gene-environment interactions and oxidative stress in acute CVD and airway disease
PIs Anne Tybjærg-Hansen and Steffen Loft. Key researchers: Marianne Poulsen (PhD student 1.2.05)RHMG+UCIPH, Ruth Frikke-SchmidtRHMG, Mette Sørensen UCIPH+ICE, Lars DragstedIFN, Zorana AndersenUCIPH, Thomas ScheikeUCIPH, Ole Raaschou-NielsenICE , Martin HvidbergNERIAE, Ole HertelNERIAE, Steen Solvang JensenNERIAE
Aim: To study effect modification by genes related to metabolism, oxidative stress, inflammation and airway defence on CVD and airway disease among 9.200 from the Copenhagen City Heart Study and in a case-cohort design based on the Diet Cancer and Health Cohort as well as case-cross over design with respect to acute events in both cohorts.
Status: Exposure assessment see WP1AB and WP4B. Target genes are under selection and assays under development. Fully automated ABI Taqman technology is available.
WP5A. Experimental study of cancer mechanisms
PI: Håkan WallinNIOH , key researchers Niklas Raun Jensen (new PhD student)NIOH+UCIPH , Herman Autrup AU, Steffen LoftUCIPH, Peter MøllerUCIPH , post.doc. Lotte Risom UCIPH , Anne Thoustrup Saber (PhD student)NIOH, Anoop SharmaNIOH, Pernille Høegh ChristensenUCIPH
Aim: To study cancer mechanism of air pollution particles by means of (transgenic) animal models
Status: Mice and rats have been exposed to diesel exhaust particulate matter by nose only inhalation, in the diet and single gavage. TNF -/- mice and NFkB reporter mice are used to elucidate the role of inflammation in carcinogenesis. The importance of DNA repair will be studied in OGG -/- and CSB -/- and OGG1 -/-Big Blue mice and Mutamouse lung epithelial cell line and in vivo in Mutamice. A new collaboration on tandem repeat mutations in germ cells induced by particle exposure has been developed with researchers from Ottawa , Canada . Papers on the role of TNF and mechanisms of oxidative stress are under publication.
WP5B Case-cohort study of colorectal cancer
PI: Ole Raaschou-NielsenICE, key researchers: Ulla Vogel NIOH , Rikke Hansen ICE+NIOH (new PhD student), Anne TjønnelandICE, Anja OlsenICE, Mette SørensenICE, Ole HertelNERIAE, Bjørn A. NexøIHG , Herman Autrup AU
Aim: To study associations between colorectal cancer and genotypes of selected polymorphisms in DNA repair enzymes, RAI and metabolism enzymes as well as effect modification in relation to association between cancer risk and exposure to air pollution assessed in WP4B.
Status: The Steering Commite of the DCH cohort has accepted the use of data and blood samples. The PhD protocol has been completed and Rikke Hansen has been enrolled as Ph.D student per August 1st, 2004. DNA samples have been purified. Herman Autrup has received DNA. The first polymorphism (GPX) has been determined and a manuscript submitted.
WP5C Case-cohort study of lung cancer
PI: Ulla Vogel NIOH key researchers: Ole Raaschou-NielsenICE, Anne TjønnelandICE, Mette SørensenICE, Bjørn A. NexøIHG , Herman Autrup AU, Ole HertelNERIAE, Steffen LoftUCIPH, Lars DragstedIFN
Aims: To study possible associations and interactions between air pollution, gene polymorphisms, biomarkers for exposure and susceptibility, and diet and smoking in the development of lung cancer in the Diet Cancer and Health Cohorts
Status (10/3 - 05): The Danish Data Protection Agency and the Scientific Ethical Commite have accepted the study. The Steering Commite of the DCH cohort has accepted the use of data and blood samples for all described purposes, except for analyses of DNA adducts, which require very much DNA. Cases and comparison group have been identified. We re-use the comparison group from the colorectal cancer study (WP 5B). Buffy coat has been found in the biobank. DNA and mRNA have been purified. The first three SNPs have been typed for the new cases and one genotype has been determined for the control group. Air pollution exposure is assessed in WP4B. Urine samples from 240 cases and a subcohort of 240 have been assayed for nucleotide damage products and a manuscript on the association with cancer risk is ready for submission.
WP6A. socio-economic aspects of air pollution
Mikael Skou Andersen NERI PA .
Aims: To develop health impact assessment related to air pollution with preference given to the issue of valuation of statistical life.
Status: A PhD student has been recruited and a protocol submitted to the University of Southern Denmark
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