2. Supercourse Environmental Exposure Assessment And Biomarkers Wael Al-Delaimy, MD, PhD

3. Environmental and Occupational Epidemiology: study the distribution of human health and disease in relationship to exposure to agents in the general and occupational environment

4. n Validity of Environmental Epidemiology & Occupational Epidemiology depends on: Assessment of exposure Assessment of effects on health Assessment of effects on health n : n Bias : an error that leads to incorrect conclusions n : the capacity of an exposure variable to measure the true exposure n Accuracy (validity) : the capacity of an exposure variable to measure the true exposure n : is a measure of the variation in the measurement error in the population n Precision : is a measure of the variation in the measurement error in the population

5. Exposure in the dictionary means: n unmasking (exposure of electoral fraud) n to light (photography) n to cold (he died of cold exposure) n position of a building (a house with western exposure) n to leave unprotected (the metal was left exposed in the rain n to give an experience (expose him to hardship)

6. n Exposure in Epidemiology: any of a subject’s attributes or any agent with which the subject may come in contact with and that may be relevant to health. n Environmental exposure: any contact between a potentially harmful agent present in the any medium, and a surface of the human body.

7. Types of exposure (time related) n Instantaneous exposure n Cumulative exposure n average exposure n peak exposure Components of exposure n a target n an agent n and contact between both

8. Dose n Definition: amount of pollution that actually crosses the border between the environment and the human body Types of Dose of exposure n potential dose n applied dose n absorbed dose n active dose n eliminated dose n net dose n accumulated dose

9. Dose estimation n Modeling: data based & physiologically based n Measurement Measurement is the classification of objects and events in which assignment of numerals to those objects and events are according to rules. Measurement is the classification of objects and events in which assignment of numerals to those objects and events are according to rules. Measurement method in epidemiology is a procedure or set of procedures designed to measure one or several of the variables of interest in an epidemiological study.

10. Exposure Measurement Error The measurement error model Z=X+e The measurement error model Z=X+e n Differential n Non-differential n Berkson error

11. Strategies of exposure assessment Types of Data Approximation To actual exposure n Quantified personal measurements n Quantified area or ambient measurements Best n In the vicinity of the residence or other sites Of activity Of activity n Quantified surrogates of exposure (e.g. estimates of Of drinking water use) Of drinking water use) n Distance from site and duration of residence n Distance or duration of residence n Residence or employment in geographic area in reasonable proximity to site of exposure.. reasonable proximity to site of exposure.. n Residence or employment in defined geographical area (e.g. county) of the site area (e.g. county) of the site. poorest

12. Biological Markers n Definition hey are cellular, biochemical, or molecular alterations that are measurable in biological media ( such as human tissues, cells or fluids). they are cellular, biochemical, or molecular alterations that are measurable in biological media ( such as human tissues, cells or fluids). Three types of measurements used for biomarkers n A. The level of the substance itself in biological media n B. The level of products of bio-transformation of the substances in the same media n C. The biological effect that result from contact of the external agent with the human body

13. Biological Markers Advantages: n improve validity and reduce bias n more individualized measurements of the subjects n specifically address the effect of one agent on a certain tissue in the body n identify individual susceptibility (e.g. genetics) n allow earlier disease detection (e.g. preventive medicine) n mechanisms of disease occurrence (e.g. cancer) n intervention trials (e.g. smoke cessation)

14. Target tissue and media for biomarkers Respiratory tract Exha- lation GI tract Saliva Feces Liver Kidney Urine Skin Exfo- liation Sweat * * oo Blood Absorption Inhalation Ingestion

15. Relation of biomarkers to exposure and disease susceptibility Internal dose BED Early response Altered structure/ function Disease Exposure Chemical Physical Biologica l Culture

16. n Interpretation of biomarkers n Statistical relationships n biological relationships n Types of Biomarkers n Markers of exposure n Susceptibility Markers n Markers of disease

17. Markers of exposure Uses n Integrate multiple portals of entry n integrate fluctuating exposure n relate time of exposure to internal dose n study acute exposure-outcome association n detect non-specific exposure hazards n use innovative biological specimens n assess real-world exposure using lab experiments measurements

18. Constraints n Most biomarkers are experimental ( need replication in multiple studies, different groups of people, various setting, over different points in time.) n Intra and inter individual variability n issues of accuracy and reliability of laboratory assays n Short 1/2 life n Intrusive n costly n lack of normal population data distribution