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Key Publications in Occupational & Environmental Health: the Year in Review Samuel M. Goldman, MD, MPH Professor of Clinical Medicine UCSF Division of Occupational & Environmental Medicine Disclosures: None Key Publications in OEM

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SLIDE 1

Key Publications in Occupational & Environmental Health: the Year in Review

Samuel M. Goldman, MD, MPH Professor of Clinical Medicine UCSF Division of Occupational & Environmental Medicine

Key Publications in OEM

Disclosures: None

Key Publications in OEM

  • Exposure to disinfectants in health care workers has been

associated with asthma

  • Very little data on associations with COPD
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SLIDE 2

Key Publications in OEM

Methods

  • Nurses Health Study II prospective cohort, 1989-forward
  • Women in 14 states, aged 25-44 (n=116,249)
  • Questionnaire every 2 years
  • Present study:
  • Still in nursing job and free of COPD in 2009 (year of first occupational

exposure hx)

  • Questionnaire data from 2009-2015
  • Exposure: a) questionnaire, b) job-task-exposure matrix (JTEM)
  • Outcome: self-reported physician-diagnosed COPD, emphysema,

chronic bronchitis; validated in subset

Key Publications in OEM

Exposure Assessment & Analysis

  • Nursing job type
  • Disinfection tasks (none/surfaces/instruments, sprays, frequency)
  • 7 most common chemicals assessed by JTEM
  • Cox regression proportional hazards models
  • Highest occupational exposure level at any timepoint, time-varying
  • Stratified by age & calendar year
  • Adjusted for race, smoking (non, ex, current & packyears), BMI
  • Sensitivity analyses: diet (Healthy Eating Index); exclude CV disease,

cancer; smoking/asthma status; interactions; stringent COPD definition

Key Publications in OEM

Results: baseline

  • N=73,262, 96% white
  • Mean baseline age 54.7 (4.6)
  • Most covariates similar across

exposure groups

  • Slightly more smoking in

“instruments” group

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SLIDE 3

Results

Key Publications in OEM

Job type Adjusted HR Education/admin 1 (ref) Outpatient 1.03 (0.81-1.32) ED or inpatient 1.24 (0.95-1.62 OR 1.38 (0.96-1.99) Any Spray Clean Surfaces Clean Instruments

Similar results in smokers & non-smokers

Results: specific chemicals

Key Publications in OEM

Discussion

  • > Weekly use of disinfectants associated with 35% increased risk of COPD
  • Dose response with frequency of use
  • surface/instrument/spray risks similar; OR jobs have highest risk
  • Risk highest for bleach, lowest for enzymatic chemicals
  • Strengths: large, longitudinal, JTEM, dose response
  • Limitations:
  • COPD definition self-reported, but….prior & current validation studies found good

agreement

  • No PPE info
  • Complete/cumulative exposure data not collected
  • Healthy worker effect?

Key Publications in OEM

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SLIDE 4

Key Publications in OEM

  • Artisanal & Small-Scale Gold Mining (ASGM) accounts for

20% of the world’s gold

  • The biggest source of mercury pollution in the world (~40%)
  • Markedly increased informal sector parallels price of gold

Key Publications in OEM

  • Amalgamation of gold and mercury since Roman times
  • Major economic opportunity: ~0.5 gram per day (~$50/gram)
  • > 16 million workers predominantly in Asia, Africa, South America
  • 5 million women and children
  • 15:1 Hg:Au, 60% released to atmosphere

Key Publications in OEM

  • https://www.youtube.com/watch?v=u6Fv6zs46A8

Whole Ore Amalgamation

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SLIDE 5

Elemental Mercury Toxicity

  • Route: inhalation >> dermal >> GI
  • Acute:
  • Pulmonary: pneumonitis, cough, dyspnea
  • CNS: headache, weakness
  • Chronic (“battery refiner’s disease):
  • Freely crosses placenta: teratogenic (CNS, renal)
  • Pulmonary fibrosis
  • CNS: fatigue, tremor, emotional lability, psychosis, myoclonus, ataxia
  • Renal: tubular necrosis, nephrotic syndrome
  • Enteritis, sialorrhea, gingivitis
  • Acrodynia (small children, pink disease): rash, extremity edema, desquamation,

photophobia, profuse sweating

Key Publications in OEM Key Publications in OEM

  • Minamata Convention of 2013
  • National action plans to reduce

sources of mercury

  • 114 parties, 41 signatories
  • Encourages legalization
  • Strategies
  • Improve Hg recovery
  • Pre-amalgamation ore concentrating
  • Gravimetric sluices
  • Hg-free approaches: direct smelting
  • Modest upfront investment required!

Key Publications in OEM

  • Automotive assembly plant closures are often unexpected (to

workers), discrete, and both culturally and economically significant events.

  • This provides a unique opportunity to estimate the consequences
  • f an acute sustained decline in economic opportunities.
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SLIDE 6

Key Publications in OEM

Background

  • Over the past 2 decades US

deaths from opiates have surged

  • Policy responses largely focused
  • n supply-side factors
  • Erosion of economic opportunity

also likely drives demand

  • Studies examining opioid

associations with unemployment and income are inconsistent

Key Publications in OEM

Methods

  • Study period 1999-2016
  • All automotive plants as of 1999, location &

date of closure, if any

  • Identified all counties within commute distance
  • Restricted to commuting zones in top quintile
  • f manufacturing job proportion (n=30 zones,

112 counties)

  • Individual-level death-certificate data
  • ICD-10 underlying & contributing cause codes
  • Outcome: Annual county-level age-adjusted

death rates from opioid overdose, ages 18-65

  • Analyses adjusted for county-level fixed

effects (e.g. rurality, SES) & calendar year

Key Publications in OEM

Baseline Characteristics

  • 10 commuting zones (29

counties) with closure

  • 20 commuting zones (83

counties) without closure

  • Baseline overdose mortality in

2001, immediately preceding the first auto plant closure

  • Other variables from 2000 US

Census

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SLIDE 7

Key Publications in OEM

Results

Opioid mortality difference overall Prescription opioid mortality difference Illicit opioid mortality difference Unadjusted trends in opioid overdose mortality by time since closure

5 years post-closure, opioid mortality had increased 85% relative to counties without a closure

Key Publications in OEM

  • Opioid mortality

differences by age & sex

  • Biggest impact by far

seen in white men aged 18-34

  • Differences in non-

whites were smaller, but imprecise

Key Publications in OEM

Summary

  • 5 years after an auto plant

closing, deaths from opiate

  • verdose increased 85%
  • Limitations: residual county-level

confounding; mediators?

  • Illustrates importance of declining

economic activity to opiate crisis

  • Structural changes to the US

economy associated with increasing mortality among less- educated adults since 1980s Solutions:

  • Short-term: community-based

interventions & treatment

  • Long-term: social policies to mitigate

disparities in economic opportunity

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SLIDE 8

Key Publications in OEM

  • 36 million with Alzheimer’s
  • 10 million with Parkinson’s
  • Both to double in 20 years
  • Genetic causes explain <

40% of AD, < 10% of PD

  • Mendelian variants have

incomplete penetrance and variable age at onset

  • Identified environmental

factors explain only a small fraction of risk

Key Publications in OEM

Neurologic Associations with Pollution

  • Proximity (50m) to major roads associated with

12% higher dementia risk (Chen et al, Lancet, 2017)

  • Urban pollution in China and US associated with

cognitive decline and white matter loss (Zhang et al,

PNAS, 2018; Cacciottolo et al, Translat Psych, 2017; Chen et al, Ann Neurol, 2015)

  • Mouse exposure to concentrated ultrafine

particles causes persistent glial activation, excitotoxicity, behavioral deficits (Allen et al, Toxicol

Sci, 2014)

  • Mexico City autopsy series found amyloid and

synuclein pathology in children, middle age

(Calderon-Garciduenas, Environ Res, 2018)

-amyloid in 38-year old -synuclein in 3-year old

Key Publications in OEM

Ultrafines & the CNS

  • Ultrafines (nanoparticles) defined as < 100nm

in diameter (0.1 microns)

  • Comprise the greatest number of airborne

particles, but have little mass

  • Road traffic contributes 90% of urban ultrafines
  • Freely enter circulation through alveoli
  • Freely enter the brain through olfactory &

trigeminal nerves

Fullerton, CA 1996

Cass, et al, 2000, Phil. Trans. R. Soc. Lond

Ultrafine ZnO in rat cortex after inhalation

Kao, et al, 2012, J Mol Neurosci

FeO in mouse

  • lfactory bulb

Hopkins, et al, 2017, Toxicol Path

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SLIDE 9

Key Publications in OEM

Magnetite

  • An iron oxide (Fe3O4) and naturally occurring

rock ore

  • First described in human brain by Kirschvank,

PNAS, 1992: 5 million crystals per gram

  • thought to form endogenously, as in bacteria
  • 35% of roadside ultrafines
  • Also from powerplants, incinerators,

biomass burning

  • Occupational: welding, machining,

driving, printers

Magnetite in roadside samples from Birmingham, UK Magnetite-like particles magnetically extracted from human brain in Mexico City & Manchester, UK

Key Publications in OEM

Iron & Neurodegeneration

  • Excess free iron (non-ferritin) is toxic to cells
  • Pro-oxidant:
  • Damage to membranes, proteins, DNA
  • Iron dysregulation in PD & AD
  • PD iron dysregulation well characterized:

increased free iron in substantia nigra

  • AD: iron associated with increased APP

expression

MRI of iron in PD brain

Ward et al, Lancet Neurol, 2014

Key Publications in OEM

Iron oxide nanoparticles in AD amyloid plaques

Transmission electron microscopy of nanoparticles in amyloid plaque Mapping of associated elements by energy dispersive X-ray analysis

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SLIDE 10

Key Publications in OEM

Summary

  • Ultrafines comprise the greatest number
  • f particulates in urban air
  • Higher levels in some work settings
  • Metal oxides make up a large proportion
  • Inhaled metal oxides cross into brain
  • Magnetite iron particles are found in human cortex from polluted areas
  • Non-ferritin iron is a potent pro-oxidant
  • Magnetite is found in association with amyloid plaques in Alzheimer’s

Djupesland et al, 2014, Therapeutic Delivery

Key Publications in OEM

Question 1:

Which cleaning chemical is associated with increased risk of COPD in the Nurses Health Study?

a) Formaldehyde b) Sodium hypochlorite bleach c) Hydrogen Peroxide d) All of the above

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SLIDE 11

Question 2:

Artisanal & Small-Scale Gold Mining (ASGM) is responsible for what proportion of worldwide mercury pollution?

a) 1% b) 5% c) 10% d) 40%

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Question 3:

In which demographic group is opiate mortality most strongly associated with auto factory closure?

a) Women aged 18-34 b) Men aged 18-34 c) Women aged 35-65 d) Men aged 35-65

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