Diesel Exhaust Health Effects
Overview
Eric Garshick, MD, MOH
Associate Professor of Medicine
VA Boston Healthcare System
Channing Laboratory, Brigham and Women’s Hospital
Harvard Medical School
Outline
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Diesel exhaust – composition, lung deposition & clearance
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Human health effects
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Cancer – Lung, Bladder
Non-malignant respiratory disease
Cardiovascular effects
Growth and development
Physiologic mechanisms:
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•
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Amplification of allergic response
Airway and systemic inflammatory and vascular responses
Future questions
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Exposure-response relationships
Is diesel exhaust unique?
New diesels
Particulate Matter Terminology
(100 nm)
Circulation 2004
Diesel Particle
Elemental
Carbon (EC)
CO2 CO
SO2 Nitrogen oxides
Organic
Carbon
(OC)
On surface
(Polycyclic Aromatic Hydrocarbons)
(PAH Compounds)
Health Effects Institute, 1995
Size Determines Where Particles Deposit
Oberdoster et al. (2005)
Typical Diesel Mass and
Number Size Distribution
cooled gases
Carbonaceous PM and
adsorbed materials
Kittleson et al. (2003)
Gas-Diesel Comparison
catalyst-gas 1981-1992
1995 medium diesel
Kleeman et al. (2000)
Similar size distributions
Diesel engine: elemental carbon > organic compounds
Gasoline engine: organic compounds > elemental carbon
Similar mutagenicity: Seagrave et al. 2002
Particle Clearance Pathways
Oberdorster et al. (2005), Nemmar et al. (2002)
Traditional Pathways
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Particle phagocytosis within a few hours
Airway mucociliary clearance - <24 hrs
Slower alveolar phase – up to 700 days with migration of
alveolar macrophages towards mucociliary escalator
Non-traditional Pathways
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Rapid translocation of particles across alveolar epithelium
Entry into circulation and lymphatics with systemic transport
Neuronal uptake (olfactory bulb) uptake and translocation to
brain
Possible dermal uptake by sensory nerves in skin
Alveolar Region
Macrophage
Fishman’s Pulmonary Diseases and Disorders, 1998, fig 2-27.
Relationship Between PM10, Carbon
Content of Macrophages, Lung Function
Kulkarni et al. (2005)
64 healthy children studied in Leicester, England
Lung Cancer Risk
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Health Effects Reviews
 USEPA (2002), CAEPA (1998), Health Effects Institute
(1995)
 ~40 studies with 20%-50% elevated risk in DE
associated occupations
 EPA – likely to be a lung carcinogen
 California – Toxic Air Contaminant
 Health Effects Institute – elevated risk not readily
explained by confounding or bias
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Newer studies
 Extension of U.S. railroad worker’s study
 Trucking Industry Particle Study
 Elevated risk observed in non-occupational settings
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Diesel exhaust is likely to be carcinogenic to humans by inhalation and
this hazard applies to environmental exposures
Conclusions are based on the totality of evidence from human, animal,
and other supporting studies
Epidemiologic studies were done in occupational cohorts, but
occupational and environmental levels overlap
Can’t derive confident quantitative estimate of cancer unit risk since
human exposure-response data are uncertain
Compared to CAEPA 1998 report - difference of opinion regarding
quantitative verses qualitative risk assessment, but not in overall
conclusions
Lung Cancer Results In Animals
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Early 1980’s to mid 1990’s diesel engines
Dose related increase at high levels of diesel
exhaust (3.5 mg/m3) in rats
Largely negative results in other rodent species
Reproduced by inhalation of other insoluble
particles without organics
Mechanism: particle overload; inflammatory
changes precede the development of lung cancer
Not relevant to humans occupationally exposed at
lower concentrations
Lung Cancer Occupational Studies
Truck Drivers
“Null”
Decreased risk Increased risk
Railroad Workers
“Null”
Decreased risk Increased risk
solid circle = smoking adjusted open circle = smoking unadjusted
Health Effects Institute Special Report 1995
Exposure Methodology Used In 39
Lung Cancer Studies
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Single job title or usual job – 18 studies
Yearly job – years of employment – 21 studies
Source of information
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Self-report, census, next-of-kin, death certificate - 21 studies
Union or work record – 17 studies
Measurement of current exposure - 3 studies
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Used to rank and validate exposure categories
Not used in primary analysis
Garshick et al. Improving estimates of diesel and other emissions
for epidemiologic studies. Boston: Health Effects Institute; 2003.
Percent Diesel Locomotives In Service:
Transition From Steam To Diesel Engines
Case-control study:
deaths 1981-82
Cohort study:
mortality 1959-1996
%
Diesel
Computerized history – starts in 1959
Railroad Worker Industrial Hygiene Survey
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Large freight railroads did not participate
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Four smaller US northern railroads agreed
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Had older equipment (1960’s vintage)
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534 personal samples collected between 19811983 in 39 jobs selected
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Respirable particles collected (similar to PM2.5)
Total and Adjusted Respirable
Particulate (ETS Adjusted)
Geometric mean & sd
Job Group (N)
Total (ｵg/m3)
ARP
(ｵg/m3)
Clerks (59)
99 (2.4)
17 (7.2)
Signal Maint (13)
58 (1.9)
49 (1.9)
Freight Engineer (55)
90 (2.3)
73 (2.3)
Freight Cond (62)
113 (1.6)
52 (2.2)
Yard Cond (32)
146 (2.0)
92 (2.0)
Machinist (110)
152 (2.0)
147 (2.3)
Woskie et al. 1988
RR Worker Case-Control Study
Garshick et al. 1987
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1,256 cases of lung cancer collected between 3/1/81 and
2/28/82 matched to controls based on age and date of death
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Smoking history from NOK
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Exposure = years of work starting in 1959 in diesel jobs
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Case age < 64 at death:
OR = 1.41 (95% CI = 1.06-1.88) for 20 years of exposure
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Case age > 65 at death:
OR = 0.91 (95% CI = 0.71-1.17) for 20 years of exposure
Railroad Worker Cohort Study
 54,973 workers age 40-64 in 1959 with 10 to 20 years of
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past railroad employment; 4,351 lung cancer deaths
through 1996
Lung cancer risk in diesel exposed jobs
(Garshick et al. 2004)
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1.40 (95% CI = 1.30-1.51)
Smoking adjusted
(Garshick et al. 2006)
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1.22 (95% CI = 1.12-1.32)
Increasing risk with years employed >=1945 (Laden et al.
2006)
Teamsters Union Study
Steenland et al. (1990)
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Central States pension fund deaths 1982-83
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Teamster job history; smoking adjusted
 Long haul driver (diesel)
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>18 years after 1959 OR=1.55 (95% CI=0.97-2.47)
 Pick-up
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& delivery driver (gas)
>18 years after 1959 OR=1.79 (95% CI=0.94-3.42)
Exposure Measurement
PM2.5 Cyclone
PM1 Cyclone
Filter Cassettes
Exposures have decreased since the
1980’s in the trucking industry
Other Supporting Studies
Urban Traffic - Nyberg et al. (2000), Nafstad et al. (2003)
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Exposure models in Stockholm and Oslo based on NO2
Elevated lung cancer risk related to NO2 levels
Air pollution - Pope et al. (2002), Laden et al. (2006)
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Relationship between PM2.5 and lung cancer risk
American Cancer Society
Cohort 1982-1998
Trucking Industry Particle Study
NCI Funding 2001-2006
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54,319 male Teamsters unionized workers employed
in 1985
Lung cancer mortality assessed through 2000
Uniform job classification and duties
Stable workforce with computerized records
 Job titles
 Terminal size and location
Comprehensive exposure assessment
Develop statistical exposure models
Goal is to provide quantitative estimates of cancer risk
Bladder Cancer
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Meta-analysis with 35 studies (Boffetta and Silverman, 2001)
 15
truck driver studies RR = 1.17 (95% CI=1.06 - 1.29)
 10 bus driver studies RR= 1.33 (95% CI=1.22 - 1.45)
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Swedish bladder cancer study (Boeffetta et al. 2001)
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Finnish bladder cancer study (Guo et al. 2004)
 Two
large population studies linking occupation with cancer
registry
 No association found
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Epidemiologic results not as consistent as for lung
cancer
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Confounding and bias can’t be fully excluded
Nonmalignant Respiratory Disease
Chronic Obstructive Pulmonary Disease
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Pulmonary retention of fine PM may result in small
airway remodeling and contribute to COPD
(Brauer et al. 2001; Churg et al. 2003)
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COPD mortality
 US
Railroad cohort RR=1.41 (95% CI = 1.25-1.55)
 Case-control study (Hart et al. 2006)
• Smoking adjusted, increased risk with greater years of
work in a diesel exposed job
Road Proximity Studies
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Altered pulmonary function and symptoms in
children related to truck traffic
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Wheeze in adults living 50 m from roadway
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Brunekreef et al. (1997); Van Vliet et al. (1997); Venn et al. (2001);
Janssen et al. (2003)
Garshick et al. (2003)
Lower rates of childhood asthma hospitalizations,
Medicaid claims, emergency room utilization
during 1996 Atlanta Olympic games
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Friedman et al. (2001)
Growth and Development
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Elemental carbon exposures associated with lower
attained lung function in children in 12 Southern
CA communities, 1993-2001
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Gauderman et al. (2004)
PAH exposures related to delayed cognitive
development, reduction in head circumference,
birth weight, respiratory symptoms (cohorts in
New York, Poland)
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Perera et al. (2005, 2006); Miller et al. (2004)
Cardiovascular Disease
Occupational studies
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Most studies from Stockholm
Fewer studies than in lung cancer literature, results not as consistent
Estimated risk increased by 20% - 60%
 Tuchsen and Endahl (1999); Bigert et al. (2004); Finkelstein et al. (2004),
Gustavsson et al. (2001), Bigert et al. (2004)
Air pollution - Pope et al. (2004), Laden et al. (2006)
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Significant relationship between PM2.5 and cardiovascular risk
American Cancer Society
Study, mortality 1982-1998
Pope el al . (2004)
Effects of Traffic
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Ultrafine PM and black carbon in patients with CAD related to
ST segment depression during exercise
 Pekkanen et al. (2002); Lanki et al. (2006), Gold et al. (2005)
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Exposure to traffic related to MI onset 1 hour later
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Increases in C-reactive protein with ultrafine, traffic - PM2.5
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Peters et al. (2004)
Ruckerl et al. (2006); Riediker et al. (2004)
Decreased heart rate variability and ventricular arrhythmia
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Schwartz et al. (2005), Peters et al. (2000); Dockery et al. (2005)
Potential Disease Pathways
1.
2.
3.
4.
5.
Allergic response amplification
Pulmonary inflammation
Systemic inflammation
Altered cardiac autonomic function
Alteration in vascular function
Conceptual Model:
Systemic Effects of PM
Cardiovascular
Pulmonary
PM
Lung Disease
Altered cardiac autonomic function and
Bai et al.(2006)
Donaldson et al. (2005)
Future Questions
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Lung cancer hazard identified but limited availability of
exposure information. Trucking Industry Particle Study
designed to estimate quantitative risk.
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What is the contribution of diesel exhaust to the non-cancer
health effects of ambient PM?
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Is diesel exhaust unique, or are health effects due to a general
effect of combustion-related PM? Are there persons more
susceptible?
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What is the relative toxicity of other sources of exhaust?
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As mass emissions are reduced the role of exhaust-related
nanoparticles that arise from condensed organics may become
more important.