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Environmental Epidemiology

Seminar on Environmental Epidemiology Integrated Master in Environmental Engineering Instituto Superior Tcnico 2nd Semester 2011/2012 Manuel Castro Ribeiro manuel.ribeiro@ist.utl.pt ext: 1441

Introduction Concepts Methods Case studies

Topics
Introduction- What is environmental epidemiology Concepts- Design, outcome, exposure Methods- Measures of exposure, disease Some case studies- Air quality

IST-UTL, March 6th 2012

Introduction Concepts Methods Case studies

Milestones
Hippocrates (460-370 BC) On Airs, Waters, and Places. Connection between different diseases occurring at different places. Ramazzini (1633-1714) The disease of workers. Occupational diseases (connection between adverse health effects on occupations exposed to dust, chemicals, metals. Richard Doll (1912-2005) Smoking and carcinoma of the lung (BMJ, 1950). Established link between smoking tobacco and lung cancer

Introduction Concepts Methods Case studies

Environmental epidemiology
Epidemiology - Study of the determinants of health-related states or events, in time, space and populations (Last). Environmental Epidemiology - Study of the determinants of health-related states or events that are influenced by environment, in time, space and populations. Environment- All that is external to human host. Environment can be divided into biological, physical, chemical, social, cultural (Last, 1995).

Introduction Concepts Methods Case studies

Systemic approach

Introduction Concepts Methods Case studies

Design
Who should be studied? population at risk? Who should be selected? Where should the study to take place? Should geographical position, altitude, meteorology, etc., be taken into account in selecting a locality? Are there existing monitoring stations or sets of data relating to the environmental factors in question? When should the study be carried out? Are seasonal effects likely to be important? Is the available time-span long enough to provide a satisfactory estimate of longterm exposures? Should exposures be averaged over months or years, or are shortterm peaks relevant in some cases? What should be measured? Single pathway (for example, via inhalation) or several ways of entry to be considered simultaneously? How are effects on health to be assessed?
In International programme on chemical safety Guidelines on studies in environmental epidemiology Url: http://www.inchem.org/documents/ehc/ehc/ehc27.htm#PartNumber:1

Introduction Concepts Methods Case studies

Assessment of exposure
Environmental Exposure- Opportunity to absorb into the body as a result of coming into contact with a environmental factor. To assess exposure we can use direct or indirect methods. Direct methods Personal monitors- devices used by individuals (workplace, home) that collect quantitative measures of personal exposure to environmental pollutants (ex: dosimeter to estimate total exposure to radiation in workplace). Biologic markers- Key molecular or cellular events that link a specific environmental exposure to a health outcome (ex: maternal urinary iodine to prevent damaging consequences on fetal and infant development). Indirect methods Combine concentrations measured in environment (through environmental monitoring) to which people may be exposed, with information on peoples activities collected through questionnaires or (time activity) diaries. 7

Introduction Concepts Methods Case studies

Environmental monitoring
Assessment of exposure (quantitative terms) Environmental monitoring , systematic collection of environmental samples for analysis of pollutant concentrations" (Berlin et al., 1979). - What pollutant(s) to study? - How long and how often should samples be taken? - Where should samples be drawn from, or instruments located? - What quality of data is needed? - Which instruments or analytical techniques should be used? The quality is determined both by sampling and by analytical procedures. If the quality of exposure assessment is below a certain minimum, the data obtained may be valueless.
Berlin, A.; Wolff, A.H. and Hasegawa, Y., ed. (1979) The use of biological specimens for the assessment of human exposure to environmental pollutants. In: Proceedings of the International Workshop CEC-WHO-EPA, 1977, The Hague, Nijhoff, 368 pp.

Introduction Concepts Methods Case studies

Assessment of outcome
Outcome- Health-related state or event under investigation. Clinical data- information collected by health professionals on diagnosis, treatment and care of each patients. Outcome definition should be clear and specific. Diagnostic tests to predict the presence of an outcome: sensitivity (proportion of patients with outcome and positive test) and specificity (proportion of patients without outcome and negative test). Use of standard clinical criteria and case definition to reduce misclassification and to reduce bias. Aggregated health data- data concerning diagnosis, treatment and care of populations (grouped data) usually published by national statistical institutes or health observatories

Introduction Concepts Methods Case studies

Conceptual risk model

True intake may differ considerably from the levels of exposure calculated from concentrations in ambient air, food, or drinking-water.
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Introduction Concepts Methods Case studies

Induction and Latency

Induction and latency periods can take hours (ex: sunburn) or years (ex: cancers)

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Introduction Concepts Methods Case studies

Methods in epidemiology

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519688/pdf/envhper00381-0018.pdf

Study design (or study protocol)- formal approach of scientific investigation. It guides researcher along the path of systematically collecting, analyzing and interpreting results. 12

Introduction Concepts Methods Case studies

Choose a study design

Descriptive studies First step in epidemiology research. Focus on description of health event in time, place and population. Can provide clues on etiologic relation between environment and disease (just hypothesis). Analytical studies Adequate to identify etiologic relation between environment and disease.

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Introduction Concepts Methods Case studies

Basic designs
Cohort study- exposure status is measured for all persons at beginning of follow up and during follow up. Usually prospective. There is no temporal ambiguity concerning exposure. Case-control (CC)- retrospective study, with controls (healthy persons) and cases (persons with disease) selected at beginning of study. Exposure are measured retrospectively. Very useful for rare diseases, specially if latent periods are long. Cross-sectional- all variables measured at a point in time (snapshot). Only suited to measure prevalence (nr of patients at a specific snapshot of time). No follow up is needed, less time consuming and costly (than some other types of study). Important for planning health services and policy analysis. Ecological- The unit of observation is a group and not a person. Official statistics (publish aggregated data) can provide data for analysis. Suppress the need to collect data individually. Easy to study large populations. Exposure of individuals are not linked to disease occurrence of those individuals.

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Introduction Concepts Methods Case studies

Basic designs

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Introduction Concepts Methods Case studies

Statistical modeling
Applied in all designs. Instruments suited to measure exposure, outcome and associations between exposure and outcome. (Ill focus on outcome measures)

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Introduction Concepts Methods Case studies

Statistical modeling
Basic statistics to deal with epidemiological data They can be descriptive or they can measure strength of association between outcome and some environmental factor. Some of the more important epidemiological indicators measured. Incidence - Nr of newly diagnosed cases during a specific time period. Prevalence - Nr new and pre-existing disease cases alive on a certain date. Risk ratio (or Relative risk) - Measures excess of disease occurrence Odds ratio - Measures excess of disease occurrence.

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Introduction Concepts Methods Case studies

Cause-effect
Several criteria exist Strength of association the relationship must be clear. Consistency observation of the association must be repeatable in different populations at different times. Temporality the cause must precede the effect. Plausibility the explanation must make sense biologically. Biological gradient there must be a dose-response relationship. Adapted from The Bradford-Hill criteria (J Roy Soc Med 1965:58:295-300)

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Introduction Concepts Methods Case studies

Cohort
Main objective is to assess association between asthma onset in children and traffic related air pollution.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569108/pdf/ehp-116-1433.pdf

217 children (10-18 yrs) with no reported asthma selected from ongoing study, were followed for 8 years (annual reports). Passive samplers for NO2 placed outside residences of children (2 weeks on winter and summer campaigns). In the end of follow up period, 30 cases of asthma have been reported. Several covariates have been collected (socioeconomic and meteorological variables). Hazard ratio (a specific type of Relative risk) was 1.29 (1.07-1.56) for an average increase of 6.2 ppb in annual residential NO2. This risk suggests that air pollution contributes to new-onset asthma.
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Introduction Concepts Methods Case studies

Case-Control
Main objective is to assess association between exposure to hydrocarbons and childhood leukemia.
http://oem.bmj.com/content/61/9/773.full.pdf+html

Hospital based, selected 280 cases (0-14 yrs at time of diagnosis) diagnosed between 1995-1999 and 285 controls (hospitalized for acute pathologies, traumatic, orthopedic, non-cancer disease) matched on age, sex and ethnicity. Standardized questionnaire on past history of exposure to hydrocarbons, neighbouring business, heavy traffic in vicinity of children's homes, parents occupations, pregnancy exposure to solvents. No clear association between maternal occupation exposure to hydrocarbons during pregnancy and leukemia or residential traffic density and leukemia. Associations were found for dwellings near petrol stations, repair garage during childhood and risk 20 of childhood leukemia (OR 4, 1.5, 10.3).

Introduction Concepts Methods Case studies

Cross-sectional
Assess exposure to microbial compounds has to occur early in life to affect maturation of the immune system, reducing risk for development of http://www.bevilatte.it/download/latte%20crudo%20alimento%20funzionale/studiolattecrudocontroasma.pdf allergic diseases. Parents of farmers children and a random sample of non-farmers children completed a questionnaire on asthma, hay fever, atopic eczema diagnosed by doctor and exposure to farming environment during pregnancy and early life (n=812). Exposure to stables and farm milk for children <1 year vs 1-5 years incidence of ashtma 1% vs 11%; hay fever 3% vs 13%. Long term and early life exposure to stables and farm milk induces a protective effect against development of ashtma, hay fever.
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Introduction Concepts Methods Case studies

Ecological
Assess association between outdoor air pollution and low birth weight.
http://oem.bmj.com/content/56/8/539.full.pdf

Unit of analysis is district . Air quality monitoring stations for TSP, SO2 and Nox. Annual average concentrations by district. Pregnancy outcomes provided by Czech Statistical Office (outcomes). Data on several socio-economic factors were collected (confounding factors). Birth weight was associated with SO2 (OR 1.1; 1.02,1.17). Association between air pollution and birth weight requires 22 further investigation.

Introduction Concepts Methods Case studies

GISA project
Assess associations between outdoor air quality and birth outcomes in Alentejo Litoral region?

http://www.biomedcentral.com/content/pdf/1471-2458-10-613.pdf

A retrospective cohort study, participants are all mothers that had one birth between 2007-2010 in Alentejo Litoral region, that accept to participate. Lichen biomonitoring program is used for ecologic assignment of personal exposure (at same sampling sites we also set four campaigns with passive samplers for SO2, NOx and O3 to validate lichen data). Questionnaire on socioeconomic and demographic, clinical data, past obstetric history, place of residence, place of work, mothers occupation during pregnancy, 23 smoking habits, diet, housing conditions (n=1655).

Introduction Concepts Methods Case studies

GISA project

Research team 1 meteorologist 1 statistician 1 sociologists 3 biologists 6 engineers 8 doctors 20 nurses

Ethical issues- data on health is sensitive. A written informed consent must be fullfilled by each participant (http://www.cnpd.pt/). Also an ethical committee must read and agree with the research (http://www.cnecv.pt/)

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Introduction Concepts Methods Case studies

GISA project

Withdrawn from study (215) a: Twins (41) No residence (45) Pregnancy outside Alentejo (129) Residence not found (12)

3200 residences referenced


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Introduction Concepts Methods Case studies

GISA project
Alccer Sal Stgo Cacm Odemira Grndola Alentejo Litoral *Portugal 2009 *Alentejo 2009 Sines 3.2% 5.7% 6.5% 6.8% 6.9% 8.2% 8.6% 10.9% Baixo peso nascena

20.0% 10.0%
N P B %

= -0,615

0.0% 0 50 100 Biodiversidade liqunica mdia

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Introduction Concepts Methods Case studies

GISA project
Other covariates that are associated with an increased risk of low birth weight: Pregnancies followed in Sines primary health centre Low weight gain during pregnancy Null parity Preterm birth Previous preterm birth Previous low birth Intrauterine growth retardation Preeclampsia Several multivariate models (glm) are being fitted and we are performing several tests to identify (and remove) confounders and effect modifiers.

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