THE IMPORTANCE OF OCCUPATIONAL AND ENVIRONMENTAL EPIDEMIOLOGY FOR THE OCCUPATIONAL HEALTH PRACTICE

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THE IMPORTANCE OF OCCUPATIONAL AND ENVIRONMENTAL
EPIDEMIOLOGY FOR THE OCCUPATIONAL HEALTH PRACTICE
6 EASOM Summer School August
31st - September 2nd, 2006

• Pier Alberto Bertazzi
• University of Milan IRCCS Maggiore Hospital
  Foundation
• Milan, Italy

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Outline

• Challenges ahead
• Epid. designs to address them
• Seveso as a case in point

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OH Practice

• Traditionally, the recognition, diagnosis and
  control of occupational risks and diseases have
  been following well specified and standardized
  procedures (regulated sometimes not just by
  medical and scientific competence but even by
  law). The OH practice was essentially called to
  comply with those regulations.

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Occup/envir. epidemiology

• Occup/envir epidemiology has mainly been serving
  OH practice by addressing particular, specific
  issues, in particular occupational cancer hazards
  identification.

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Changes at the workplace

• Today, things have changed and still are
  changing at work, in science and in medicine.
• Workplace hazards are less obvious to identify
  and to measure.
• Occupational factors increase the risk of
  common diseases (a-specific effects)
• Specific effects are vague, psychological,
  subjective (distress, discomfort).
• Genetics and behaviour are becoming more and more
  relevant.
• Working population is changing in terms of age
  structure, sex composition, and ethnicity.

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Change in hazards

• Workplace hazards are less obvious to identify
  and measure (and hence to control)
• Population vs. sick individual approach
• Longitudinal observation of exposed
  (exposure-dose-early effect-disease)

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Change in effects I

• Occupational factors increase the risk of common
  diseases (a-specific effects).
• Populations comparison (exposed vs. reference)
• Small increase in risk visible only in relative
  terms (vs. background)
• Need to observe large groups.

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Change in effects II

• Specific effects are vague in nature, mainly
  psychological, subjective (distress and
  discomfort).
• Accuracy and validity of diagnostic means and
  procedures
• Surveillance of healthy population not of
• sick individuals
• Need to observe large groups.

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Novel causative components

• Genetic and behavioural components are becoming
  more and more relevant.
• Gene environment interaction as population
  effect
• Psychic and psychosomatic effects (lagoon of
  causative factors)
• Avoid bias, control confounding, consider
  interactions.

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Working population change

• Working population is changing in terms of age
  structure, sex composition,
• and ethnicity.
• Relevance of inherited and acquired
  susceptibility.
• Multi-component causative web
• Targeted interventions including re-training and
  health promotion

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The core type of activity needed in such a
changing context

• OBSERVATIONAL STUDY OF EXPOSED POPULATION OVER
  TIME
• This is
• .What we ought to contribute to, when we
  practice Research
• .What we have to teach to our students
  Teaching
• .What can confer appropriateness and
  effectiveness
• to OH practice and intervention Practice
• .What makes evaluation possible
  Evaluation

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• PRIORITIES IN OCCUPATIONAL HEALTH RESEARCH - UK
• Natural history of work related ill health
• Musculoskeletal disorders (back upper limb)
• Asthma
• Accidents
• Skin disease
• Vibration induced disease
• Suicide
• Depression
• Hearing loss
• Audit in occupational health screening
  procedures
• Environmental impact of industrial activity
• Community gt individual level
• Stress related disease
• Neuro-psychological effects
• Cost-effectiveness of occupational health
• Risk assessment
• Reproductive hazards

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Need to answering new questions about safety and
health at the workplace

• Which study design?
• Depends on the exposure and nature of health
  outcome of interest, and on feasibility

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Cohort

• Follow up of an exposed population and
  determination of subsequent incidence of health
  outcomes
• Historical - long induction and latency period
• Prospective short temporal relation between
  exposure and subsequent risk

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Cross sectional

• Comparison of disease prevalence among groups
  classified according to exposure.
• Study of persistent conditions (rather than
  transient and reversible)
• Repeated measurement study

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Case-control

• Exposure comparison between an index case group
  and a reference group of persons free of the
  disease at the time of case definition
• Nested within a cohort
• Community based

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Case-cohort

• Multiple case groups and a common comparison
  group, reference sub-cohort, random sample of
  the source population (cohort)
• Efficient in testing associations with multiple
  health outcomes

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Case-crossover

• Comparison of cases exposure immediately before
  their events with exposure that occur at other
  typical times. Each case serves as his/her
  matched control.
• Suitable for risk factors of health outcomes that
  occur in close temporal sequence to exposure
  (disease triggers).
• Full control of time invariant confounders
  (genetics)

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(Mc Lure 1991)
CASE CROSSOVER DESIGN
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In the light of the specific issues we are
facing today in OSH..

• Strategy of choice appears to often be a
  combination of epidemiologic studies.
• The best way to illustrate and to teach this is
  through examples (hypothetical, at least) of
  complex multi-causal effects and given workplace
  exposure or case studies of complex exposures
  related to multiple effects (e.g., the Seveso
  accident).

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Lombardy Region
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ICMESA, the Seveso Accident plant
Dept. B Production of 2,4,5-trichlorophenol TCP
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Seveso, Italy, 1976
TCP production plant
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
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Seveso, Italy, 1976
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DESIGN and CONDUCT ISSUES

• Exposure type, entity, duration.
• Exposed/Pop. at risk definition, identification.
• Effects type, latency, diagnosis.
• Follow-up contact, observation, means and
  procedures.
• Study type of design, study population (sample),
  duration.
• Reference population control of confounding.
• Information validity and quality.
• Analyses and interpretation.
• Communication scientific and social.

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OBJECTIVES ADDRESSED AFTER THE ACCIDENT

• Ascertaining the exposure, its nature and
  characteristics, the extent of contamination and
  number of people involved
• Managing the risk with preventive measures for
  people and their environment
• Planning and conducting health surveillance
  programs

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EXPOSURE ASSESSMENT
EMISSION SOURCE
ECOLOGICAL AND ENVIRONMENTAL MEASUREMENTS

• pollutant type
• amount released

• surface soil
• deeper soil layers
• water
• airborne dust
• vegetation
• animals
• cows milk

HUMAN EXPOSURE/ DOSE

• personal habits and
• activities
• chloracne
• biological samples

HEALTH EFFECTS

• early and mid-term
• long term

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Exposure
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The Seveso area
Bertazzi et al., Environ Health Perspect 1998
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The Seveso area
Bertazzi et al., Environ Health Perspect 1998
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The Seveso area
Bertazzi et al., Environ Health Perspect 1998
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The Seveso area
Bertazzi et al., Environ Health Perspect 1998
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TCDD plasma levels, 1976
Needham et al., Chemosphere 1998
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Plasma TCDD after 20 years
TCDD Range 1.0-89.9 ppt, lipid adjusted
Landi et al., Lancet 1997
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Early cross-sectional studies
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CHROMOSOMAL ABERRATIONSIN LYMPHOCYTES, 1977
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CONGENITAL MALFORMATIONSZONES ABR vs. REFERENCE
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CHLORACNE CASES 1976-1977
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Incidence studies
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Mortality (Zone AB)
Analysis adjusted for age and sex
Bertazzi et al., Am J Epidemiol 2001
 
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Cancer incidence (Zone AB)
Analysis adjusted for age and sex
Pesatori et al., Ind Health 2003
 
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OFFSPRING SEX RATIO AND PARENTAL TCDD LEVELS
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Case-control retrospective study
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Higher TCDD exposure The only determinant of
chloracne?
Chloracne Case-Control Study

• 101 chloracne cases
• Median age 8 years
• 211 controls
• Enrollment 1993-1998

Opportunity to identify susceptibility
factors!
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Mean plasma TCDD
Chloracne
Chloracne
Controls
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Potential Susceptibility Factors
TCDDgt10 ppt
Analysis adjusted for age, sex and zone of
residence
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Health conditions after 20 years

• No differences between chloracne cases
  healthy controls
• Allergic diseases
• Gastrointestinal disorders
• Infectious diseases
• Endocrine disorders
• Respiratory diseases
• Offspring health status

Baccarelli et al., Br J Dermatol, 2005
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Late cross-sectional studies
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Subclinical conditions after 20 years
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IgG plasma levels
p0.03
p0.01
Baccarelli et al., Environ Health Perspect 2002
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Plasma TCDD vs. IgG
Baccarelli et al., Environ Health Perspect 2002
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Need to rediscover population approach coupled
with high risk individual approach

• Epidemiology has largely ceased to function as
  part of a multidisciplinary approach to
  understanding the causation of disease in
  populations and has become a set of generic
  methods for measuring associations of exposure
  and disease in individuals. .
• (for studying) decontextualized individual risk
  factors, rather than to study population factors
  in their social and historical context.
• We seem to be using more and more advanced
  technology to study more and more trivial issues,
  while the major causes of disease are ignored.
  Epidemiology must reintegrate itself into public
  health and must rediscover the population
  perspective.
• (N. Pearce, Am J Public Health, 1996, 86678-683)

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PREGNANCY LOSS RATE,1976-1977, BY TRIMESTER
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Effect of plasma TCDD
Plasma TCDD
AhR
ARNT
AhR
EROD
DRE

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CYP1A1
CYP1B1
Uncultured cells
TCDD stimulated Cells
Baccarelli et al., Tox Lett 2004