SupercourseSupercourse

Environmental Environmental Exposure Assessment Exposure Assessment And BiomarkersAnd Biomarkers

Wael Al-Delaimy, MD, PhDWael Al-Delaimy, MD, PhD

EnvironmentalEnvironmental and and OOccupationalccupational Epidemiology: Epidemiology: study the distribution of study the distribution of human health and disease in human health and disease in relationshiprelationship to exposure to to exposure to agents in the general and agents in the general and occupational environmentoccupational environment

Validity of Environmental Epidemiology & Validity of Environmental Epidemiology & Occupational Epidemiology depends on: Occupational Epidemiology depends on: Assessment of exposureAssessment of exposure

Assessment of effects on healthAssessment of effects on health Bias : : an error that leads to incorrect

conclusions Accuracy (validity) : the capacity of an : the capacity of an

exposure variable to measure the true exposureexposure variable to measure the true exposure Precision : is a measure of the variation in the : is a measure of the variation in the

measurement error in the populationmeasurement error in the population

Exposure in the dictionary means:Exposure in the dictionary means:

unmasking (exposure of electoral fraud) unmasking (exposure of electoral fraud) to light (photography) to light (photography) to cold (he died of cold exposure)to cold (he died of cold exposure) position of a building (a house with position of a building (a house with

western exposure)western exposure) to leave unprotected (the metal was to leave unprotected (the metal was

left exposed in the rainleft exposed in the rain to give an experience (expose him to to give an experience (expose him to

hardship) hardship)

Exposure in EpidemiologyExposure in Epidemiology: any : any of a subject’s attributes or any of a subject’s attributes or any agent with which the subject may agent with which the subject may come in contact with and that may come in contact with and that may be relevant to health.be relevant to health.

Environmental exposureEnvironmental exposure: any : any contact between a potentially contact between a potentially harmful agent present in the any harmful agent present in the any medium, and a surface of the medium, and a surface of the human body.human body.

Types of exposure Types of exposure (time related)(time related) Instantaneous exposureInstantaneous exposure Cumulative exposureCumulative exposure average exposureaverage exposure peak exposurepeak exposure

Components of exposureComponents of exposure a targeta target an agentan agent and contact between bothand contact between both

DoseDose Definition: amount of pollution that Definition: amount of pollution that

actually crosses the border between the actually crosses the border between the environment and the human bodyenvironment and the human body

Types of Dose of exposureTypes of Dose of exposure potential dosepotential dose applied doseapplied dose absorbed doseabsorbed dose active doseactive dose eliminated doseeliminated dose net dosenet dose accumulated doseaccumulated dose

Dose estimationDose estimation Modeling: Modeling: data based & physiologically data based & physiologically

basedbased

MeasurementMeasurement Measurement Measurement is the classification of objects is the classification of objects

and events in which assignment of numerals to and events in which assignment of numerals to those objects and events are according to rules.those objects and events are according to rules.

Measurement method in epidemiology Measurement method in epidemiology isis a a procedure or set of procedures designed to procedure or set of procedures designed to measure one or several of the variables of measure one or several of the variables of interest in an epidemiological study.interest in an epidemiological study.

Exposure Measurement ErrorExposure Measurement Error

The measurement error model The measurement error model Z=X+eZ=X+e

DifferentialDifferential

Non-differential Non-differential

Berkson errorBerkson error

Strategies of exposure assessmentStrategies of exposure assessment

Types of Data Approximation To actual exposure

Quantified personal measurements Quantified personal measurements Quantified area or ambient measurements BestQuantified area or ambient measurements Best In the vicinity of the residence or other sitesIn the vicinity of the residence or other sites Of activityOf activity Quantified surrogates of exposure (e.g. estimates of Quantified surrogates of exposure (e.g. estimates of Of drinking water use)Of drinking water use) Distance from site and duration of residence Distance from site and duration of residence Distance or duration of residenceDistance or duration of residence Residence or employment in geographic area inResidence or employment in geographic area in reasonable proximity to site of exposure..reasonable proximity to site of exposure.. Residence or employment in defined geographicalResidence or employment in defined geographical areaarea (e.g. county) of the site(e.g. county) of the site.

poorest

Biological MarkersBiological Markers DefinitionDefinition they are cellular, biochemical, or molecular hey are cellular, biochemical, or molecular

alterations that are measurable in biological alterations that are measurable in biological media ( such as human tissues, cells or fluids). media ( such as human tissues, cells or fluids).

Three types of measurements used for Three types of measurements used for biomarkersbiomarkers

A. The level of the substance itself in biological A. The level of the substance itself in biological mediamedia

B. The level of products of bio-transformation B. The level of products of bio-transformation of the substances in the same mediaof the substances in the same media

C. The biological effect that result from contact C. The biological effect that result from contact of the external agent with the human bodyof the external agent with the human body

Biological MarkersBiological MarkersAdvantages:Advantages: improve validity and reduce biasimprove validity and reduce bias more individualized measurements of the more individualized measurements of the

subjectssubjects specifically address the effect of one agent on specifically address the effect of one agent on

a certain tissue in the bodya certain tissue in the body identify individual susceptibility (e.g. genetics)identify individual susceptibility (e.g. genetics) allow earlier disease detection (e.g. preventive allow earlier disease detection (e.g. preventive

medicine) medicine) mechanisms of disease occurrence (e.g. mechanisms of disease occurrence (e.g.

cancer)cancer) intervention trials (e.g. smoke cessation)intervention trials (e.g. smoke cessation)

Target tissue and media for Target tissue and media for biomarkersbiomarkers

Respiratory tract

Exha-lation

GI tract

Saliva

Feces

Liver

Kidney

Urine

Skin

Exfo-liation

Sweat

* * oo

Blood

Absorption Inhalation Ingestion

Relation of biomarkers to exposure Relation of biomarkers to exposure and diseaseand disease

susceptibility

Internal dose

BEDEarly

response

Altered structure/function

DiseaseExposure

ChemicalPhysicalBiological

Culture

Interpretation of biomarkersInterpretation of biomarkers Statistical relationshipsStatistical relationships biological relationshipsbiological relationships

Types of BiomarkersTypes of Biomarkers Markers of exposureMarkers of exposure Susceptibility MarkersSusceptibility Markers Markers of diseaseMarkers of disease

Markers of exposureMarkers of exposure

UsesUses Integrate multiple portals of entryIntegrate multiple portals of entry integrate fluctuating exposureintegrate fluctuating exposure relate time of exposure to internal doserelate time of exposure to internal dose study acute exposure-outcome associationstudy acute exposure-outcome association detect non-specific exposure hazardsdetect non-specific exposure hazards use innovative biological specimensuse innovative biological specimens assess real-world exposure using lab assess real-world exposure using lab

experiments measurementsexperiments measurements

ConstraintsConstraints Most biomarkers are experimentalMost biomarkers are experimental((need replication in multiple studies, different need replication in multiple studies, different

groups of people, various setting, over different groups of people, various setting, over different points in time.)points in time.)

Intra and inter individual variabilityIntra and inter individual variability issues of accuracy and reliability of issues of accuracy and reliability of

laboratory assays laboratory assays Short 1/2 lifeShort 1/2 life Intrusive Intrusive costlycostly lack of normal population data lack of normal population data

distributiondistribution

Scatterplot of the association between nicotine in hair samples taken

at baseline and 3-6 months later for the same individuales

(Baseline samples ) Log10 ng nicotine/mg hair

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Log

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