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Environmental Exposure Assessment Workshop for Population Studies
Banff, AlbertaFeb. 2008
Making choices regarding Making choices regarding characterization of environmental characterization of environmental
exposuresexposures
J.R. BrookEnvironment CanadaUniversity of Toronto
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E
Environmental
E
Exposure
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Canadian Healthy InfantLongitudinal Development
The Challenge of Assessing The Challenge of Assessing ExposureExposure
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Environmental exposures that have been associated with Environmental exposures that have been associated with the development or exacerbation of childhood asthmathe development or exacerbation of childhood asthma
Fireworks smoke exposure Diet (Vit D, fish consumption)
Ascaris infection, other parasites (protective?) Birth Order/Sibship size
Breastfeeding (mixed) Geography
Outdoor pollen and fungi Household cleaners/pesticides
Early childhood infections Weather/Meteorology
Mould and moisture Housing characteristics
Environmental tobacco smoke Stress
Vaccination Status Endotoxin
Outdoor PM air pollution, traffic pollution Socioeconomic status
Indoor PM air pollution Phthalates, PAHs
House dust mite allergens Pet allergens (cat, dog)
Caesarian section Pest Allergens (cockroach, mouse)
Antibiotic use Chloramines (swimming pools)
Birth weight Violence
Parental asthma/atopy Atopy
Race/Ethnicity Maternal Smoking
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There has been decreases in the cost of obtaining detailed genetic information and advances in computational methods.BUTExposure measurement remains expensive and more detail = more expensive Limitations due to ethical considerations
Compromise is necessary
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Advances in exposure Advances in exposure characterizationcharacterization
• Measurement technologies– Dust collection approaches– Chemical analysis of dust– Small passive and active samplers– Biomarkers– Greater coverage through satellite observations
• Models– Empirical and physical outdoor air models– Indoor Infiltration models– Probabilistic exposure models– Greater integration
• Questionnaires– More detail (different questions, behaviour)– Ongoing validation
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Strategies for prioritizing the Strategies for prioritizing the exposures of interestexposures of interest
• Public Health Importance– exposures that are modifiable, are
common across the population and are hypothesized (or shown) to be associated with the development of asthma
• Measurement Capability– a validated method for characterizing the
exposure is available and resources are available to collect the desired data
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• Biological Mechanisms– focus on an exposure that is hypothesized to act
through the same biological pathway as an other exposures that has been associated with asthma
– help develop biomarkers to quantify exposure and/or effect based upon features of the biological pathway
• Potential for Data Pooling– measure the same exposures at the same time
points using the same methods so that the resulting data can be combined with other studies
– requires specific knowledge of the other studies and flexibility in the design of the new study
• larger sample size• potential for greater variability in exposure
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Factors Controlling Power inFactors Controlling Power inGene X Environment StudiesGene X Environment Studies
• exposure prevalence– study populations with large exposure prevalence
and contrasts
• measurement error– can be directly influenced by study design– reducing error is an efficient way to improve power
• true effect size– study environmental factors or genetic effects that
are hypothesized to be large based on animal (or microarray) studies
• genotype (phenotype) prevalence– study populations with large prevalence
Wong et al. 2003, IJE
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Reducing Measurement ErrorReducing Measurement Error• well-defined research questions• more repeat measurements of exposure• better timing of exposure measurements• use of less expensive exposure surrogates
that are better correlated with the specific outcome of interest
• more accurate/specific genotyping, consistent phenotyping
• improved understanding of the mechanism of effect (epigenetics)– Helps target the desired exposure
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Technological AdvancesTechnological Advances
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Integrating Sources of Exposure Integrating Sources of Exposure Info.Info.
Measurements + Model + Questionnaires = Measurements + Model + Questionnaires = MODELMODEL
Measurements
Questionnaires
Long
term
tim
e-in
tegr
ated
ex
posu
res
But
at s
peci
fic ti
me
poin
ts (
?)
LUR – Land-Use Regression
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Annual Average NOAnnual Average NO22 Observed from Observed from Space Space
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TorontoToronto
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Best Resolution of Current AQ Best Resolution of Current AQ ModelsModels
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Dichotomous Sampler
TEOM
Air Quality ModelMeasurement
networks
Empirical models
‘Fused’ spatio-temporal
concentration/exposure
Satellite observations
Hi-res Emissions
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Issues to consider when applying Issues to consider when applying LUR to studies of air pollution LUR to studies of air pollution
and healthand health • differential exposures at home,
outdoors and in the workplace• subject mobility• the relevant time period exposure
(and duration of relevant exposure)• exposures to multiple pollutants • tracking effect modifiers• variability in infiltration indoors
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Is there a more-direct measure?Is there a more-direct measure?
012345678
0 5 10 15 20
Vehicle exhaust tracer in dust (mg/kg)
R2=0.01
NO2 Outside Home (ppb)
Adj.-NO2 Outside Home (ppb)
012345678
0 5 10 15
R2=0.43Air exchange rate adjusted
detached garageN N
Att. w/door
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• Standard biological indicators of allergens• Isolate community DNA for new scans
26.00 28.00 30.00 32.00 34.00 36.00 38.00 40.00 42.00 44.000
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Time-->
Abundance
Ion 191.00 (190.70 to 191.70): 9817BM.D
26.00 28.00 30.00 32.00 34.00 36.00 38.00 40.00 42.00 44.000
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Abundance
Ion 191.00 (190.70 to 191.70): EC100CB.D
Lube oil98-17
PM 98-17US063
• Chemical Indicators ofmotor vehicle exhaust and phthalate exposures
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Combining Existing CohortsCombining Existing CohortsCompromises, compromisesCompromises, compromises
Highest common denominatorHighest common denominator• Outdoor air exposure can often be
reconstructed• Residence at recruitment• Residence during pregnancy and in early life• Complete residence history
– Proximity to source(s)– Dispersion models
• More validation is desired
• Questionnaires – How specific, how validated, how often ?– Geographic/cultural differences in their meaning
• Evaluation of similarities/differences is desired
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How do we optimize our How do we optimize our environmental exposure environmental exposure
characterization?characterization?(for G x E research)(for G x E research)
• Many options– Just need time and money
• Efficiency– Comes from asking the right
question(s)
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PARSIFAL Schram-Bijkerk et al. 2006 INDOOR AIR
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Exposure information that Exposure information that can be collected from can be collected from
questionnairesquestionnaires Housing characteristicsAge, building materials, ventilation systems, below-grade characteristics, renovations, cooking habits, fuel type, swimming pool (chlorine)
Indoor materialsVinyl flooring, carpeting, VOC-based finishes and glues, moisture capturing nutrient rich materials (e.g. dry wall)
MicroenvironmentsTime in traffic, ETS, mother’s occupation, daycare, school ……>> occupation
Animals & PestsCats, dogs, farm animals, rodents, cockroaches, arthopods
Surrounding EnvironmentVegetation (plants, trees, grasses), traffic levels, industrial presence
Consumer products in the homeFurniture, electronics, blinds, cleaning agents, pesticides, herbicides
Dampness and mouldPresence, area of concern, moisture evidence
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Exposure information that Exposure information that can be collected from can be collected from
questionnairesquestionnaires Dampness and mould Presence, area of concern, moisture evidence
Activities Time spend indoors, time spent outdoors, time on floor, frequency
of hand-to-mouth contact, storage of toys, sunlight exposure
Socioeconomic factors Income, stress
Diet Food frequency, containers, cooking methods
Infections Viruses, upper respiratory infections
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Nitrogen Dioxide vs. Traffic Nitrogen Dioxide vs. Traffic pollutionpollution
200
400
600
800
1000
Ho
pa
ne
s (
pg
m-3)
NO2 (r=0.67 )
0 10 20 30 40 50 60
NO2 (ppb)