Transcript Particulate Matter Toxicology - AOEC

Particulate Matter Toxicology
Michael J. Wernke, R.Ph., Ph.D; Marci Balge, RN, MSN, COHN-S;
Scott Phillips, MD, FACP, FACMT, FAACT
This educational module was produced by Michael J. Wernke, R.Ph., Ph.D, Scott
Phillips MD, FACP, FACMT, FAACT and Marci Balge, RN, MSN, COHN-S for The
University of Texas Health Science Center at San Antonio (UTHSCSA)
Environmental Medicine Education Program and South Texas Environmental
Education and Research Program (STEER-San Antonio/Laredo/Harlingen,Texas)
Administrative support was provided by the Association of Occupational and
Environmental Clinics through funding to UTHSCSA by the Agency for
Toxic Substances and Disease Registry (ATSDR), U.S. Department of Health and
Human Services. Use of this program must include acknowledgement of the
authors, UTHSCSA and the funding support.
For information about other educational modules contact the UTHSCSA
STEER office, Mail Code 7796, 7703 Floyd Curl Drive, San Antonio,
Texas 78229-3900,(210)567-7407.
Case Presentation
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An 11-year-old boy presents with his mother
with complaints of wheezing, a productive
cough with phlegm, and a runny nose
The boy has been previously diagnosed with
asthma and is currently treated with an
albuterol inhaler and Singulair
Case Presentation (continued)
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The boy has had good control of his asthma
over the past several months, but in the past
few weeks he has significantly increased his
inhaler use, especially after playing outdoors
Symptoms worse outdoors; feels better when
in air conditioned spaces
Case Presentation (continued)
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Family lives in a rural area along the Texas-Mexico
border; the primary commodity grown in this area is
sugarcane
Over the past few weeks workers have been setting
the fields of sugarcane ablaze; onset of worsening
asthma symptoms corresponded with the burning of
the sugarcane
Mother questions link between the burning and her
son’s asthma and additionally questions why the
workers are burning the crop prior to harvest
Case Presentation (continued)
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Mother also reports that since the fires began
there has been a lot of smoke and haze in the
air
Local media have been cautioning people
with respiratory conditions to remain indoors
and for others to limit their activity outdoors
Case Presentation (continued)
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Physical examination reveals a clear nasal
discharge, expiratory wheeze, and a product
cough but is otherwise unremarkable. The
boy is afebrile. Other than the respiratory
complaints, the child has no other health
complaints.
Case Presentation (continued)
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Impression: exacerbation of asthmatic symptoms
related to the burning of nearby and perhaps distant
sugarcane fields
Sugarcane growers burn their fields in preparation
for harvest – removes unwanted material (e.g.,
leaves) and increases yield
The burning also generates considerable
smoke/particulate matter
Case Presentation (continued)
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Advise child to remain indoors in air-conditioned
environments until burning ceases
Use a dust/allergy mask when outdoors; limit time
and activity outdoors until burning ceases
Use asthma medications as directed and return after
air quality improves for re-evaluation
Questions To Consider
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What is particulate matter and how is it
defined?
Can exposure to particulate matter cause or
exacerbate asthma or other respiratory
conditions?
Are there other health effects associated with
exposure to particulate matter?
Questions to Consider
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Are there certain segments of the population who are
more sensitive to the adverse health effects of
particulate matter?
Are there safe levels of exposure to particulate
matter – if so, what are these?
Where can one find information concerning the
concentration of particulate matter in their area?
Airborne Particulate Matter
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A major public health issue
Estimated to cause 500,000 excess deaths
annually worldwide
Associated with adverse effects on the
pulmonary and cardiovascular system
May cause toxicity at or below NAAQS
Airborn Particulate Matter
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Not a unique or single substance
A mixture of organic, inorganic, and
biological materials of various size and shapes
May have bound to it other substances (e.g.
metals, PAH) that cause toxicity
Composition varies by regionally, seasonally,
and daily
Airborne Particulate Matter
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Local and distant sources can contribute to the
composition
Chemical composition provides clues regarding
source (e.g. burning tires as a fuel for firing bricks
along Texas-Mexico border has been shown to affect
air quality of the Paso del Norte airshed in general
and El Paso, Texas in particular
El Paso border; Juarez, Mexico
Airborne Particulate Matter
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Greatest area of interest lies in
nanotechnology and nanoparticulates
Large number of people with potential
exposure
Nanoparticules are small enough to directly
enter cell thereby possibly leading to toxicity
Lecture Overview
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Classification
Existing air standards
Dose considerations
Deposition and clearance in lung
Health effects
Particulate Matter - Regulatory
Classification
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Regulatory classifications include total dust or
coarse, fine or ultrafine (nanoparticulate)
based on MMAD
Total dust < 100 µm
Coarse 2.5 - 10 µm
Fine 0.1 – 2.5 µm
Ultrafine < 0.1 µm
NAAQS
Particle Type
Annual Mean
24-Hour Max
PM10
50 µg/m3
150 µg/m3
PM2.5
15 µg/m3
65 µg/m3
NAAQS
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Large database demonstrating acute and chronic
health effects at NAAQS but the reason is not clear
Health effects associated with measures of mass
(µg/m3) rather than by composition or nominal size.
Day-to-day fluctuations in the mass concentration of
10 µg/m3 increases mortality by abut 0.6 to 1%
ACGIH Classification
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Inhalable particulate (< 100 µm)
Thoracic particulate (0 – 25 µm)
Respirable particulate (0 – 10 µm)
Occupational Guidelines (TLV) – 3 mg/m3 for
respirable particulate and 10 mg/m3 for
inhalable particulate
Sampling for Particulates
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Area samples
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Useful for identifying source and general
background exposure
Depending on a number of factors, such as
distance from source, time spent outdoors,
weather patterns, area samples may under- or
overestimate any one person’s exposure
Sampling for Particulates
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There are a number of continuous air
monitoring stations throughout the state of
Texas, some of which are located on the
Texas-Mexico border
Stations do report particulate air matter
concentration (PM10 and PM2.5)
Texas Commission on Environmental Quality
(www.tceq.state.tx.us)
Sampling for Particulates
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Personal samples
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Air collected within 25 cm of the nose and mouth
Provide a good measure as to that individual’s
exposure
Expensive/may not be feasible in a community
Need to assess representative groups
Dose Determinations
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Many measures of dose
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Exposure dose (De)
Inhaled dose (Di)
Total deposited dose (Dd)
Regional deposited dose (Dr)
Dose deposited per regional surface area (Drsa)
Dose Determinations
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Various dose matrices differ in the amount of
information considered
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De = C x T
Drsa = C x T x Vm x I x DFr/Sr
In clinical setting such calculations are not
important; only likely to know average
concentration and exposure duration if
anything at all
Individual Factors Affecting Dose
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Normal individuals with airway anatomies or
breathing characteristics that are extreme in
the health population distribution (outliers)
Very young, very small, or obese individuals
Lung disease (e.g. COPD; Asthma)
Individual Factors Affecting Dose
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Physical activity
Impaired clearance
Proximity to source
Behavioral changes, such as curtailing
physical activity outdoors, remaining in airconditioned environments, use of air filters
can lower one’s dose.
Particulate Matter Deposition
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Particle size determines region of respiratory
tract where a particle will be deposited.
Deposition of particles on the surface of the
respiratory system brought about by a
combination of lung anatomy and patterns of
air flow
Particulate Matter Deposition
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5 – 30 µm particles deposited in nasopharynx
by inertial impaction
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Abrupt directional changes and high velocity air
flow force these larger particle to impact the
airway surface
Recent data indicates that very fine particles
(<0.01 µm) are efficiently trapped in the upper
airways by diffusion
Particulate Matter Deposition
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1 – 5 µm particles deposited in the
bronchiolar region via sedimentation
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In this region the airways are small, changes less
abrupt, and air flow velocity low, allowing
particles to settle out of the airflow and onto the
airway surface
Particles ≤1 µm deposited in the alveolar
region via diffusion
Particulate Matter Deposition
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Factors affecting deposition include:
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Inactivity (periods of quiet breathing)
Physical activity
Breath holding
Pulmonary disease (e.g. chronic bronchitis)
Irritants (e.g. tobacco smoke)
Particulate Matter Clearance
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Lung’s main defense mechanism
Rapid clearance decreases time available to
cause damage or permit systemic absorption
Does not necessarily imply clearance from
body
Particulate Matter Clearance
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Particles removed from the respiratory system
may be transported
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To the stomach/GI system and absorbed
To the lymphatics and enter venous circulation
The pulmonary vasculature and absorbed
Coughing/nose blowing can completely
removed deposited particles
Particulate Matter Clearance
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Nasal Clearance
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Anterior portion- wiping or blowing
Other portions – mucociliary transport
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Insoluble particles cleared within 1 hour
Soluble particles may be dissolved and absorbed
before they can be removed
Olfactory regions or areas damaged by infection,
illness, or toxic injury - uncertainty
Particulate Matter Clearance
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Tracheobronchial Clearance
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Mucociliary escalator transports particles and
particle-laden macrophages to the oropharynx
where they are swallowed
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Relatively rapid and complete within 24-48 hours
Infection and other injuries can greatly impair
clearance from this area
Particulate Matter Clearance
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Pulmonary Clearance
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Several mechanisms:
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Mucociliary escalator
Phagocytized by macrophages and cleared via mucociliary
escalator
Phagocytized by macrophages and cleared via lymphatics
Substances may dissolve from surface of particle and be removed
via blood or lymphatics
Direct penetration of epithelial membranes (ultrafine particles)
Particulate Matter Clearance
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Uptake and transport via sensory neuronal
axons
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Area of intense research
Supported by research in laboratory animals
using dye particles, polio virus particles, and 14Cultrafine particles
Concern entails direct entry of potentially toxic
substances into the CNS
Particulate Matter Health Effects
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The adverse effects of particulate matter are
primarily observed in the pulmonary and
cardiovascular systems, involving both
morbidity and mortality. We’ll begin our
discussion on with the pulmonary system and
then talk about the cardiovascular system.
Particulate Matter Health Effects
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Asthma
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Abundant evidence from epidemiological studies,
including studies along the Texas-Mexico border, that
particulate matter air pollution contributes to
exacerbations of asthma.
Particles have been linked to worsening of symptoms,
decrements in lung function, increased hospital
admissions, and increased medication (e.g. inhaler) use.
Particulate Matter Health Effects
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Asthma
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Mechanism of exacerbation not fully elucidated
Possibly mediated by particulate matter-induced
inflammation
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Direct injury
Activation of cellular hose defense pathways leading
to inflammation
Particulate Matter Health Effects
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Asthma
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Support for inflammatory hypothesis
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Evidence that outdoor air particulates cause
inflammation in the lungs
Inflammation known to play a critical role in
obstructive airway disease such as asthma
Particulate Matter Health Effects
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Asthma
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Asthmatics considered at risk for exacerbation
due to ambient particulate matter because
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Obstructive lung disease like asthma increase airway
deposition of fine and ultrafine particles
Nonspecific airways responsiveness
Particle-induced inflammation may increase airway
responses to allergen exposure.
Particulate Matter Health Effects
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COPD
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Perhaps mediated via inflammatory processes
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Hypothesis is that particulate matter activates
neutrophils and macrophages, causing them to release
proteases and reactive oxygen species, both of which
have been implicated in the lung parenchymal
destruction that defines emphysema.
Particulate Matter Health Effects
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Other Respiratory Ailments
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Long-term exposure to particulate matter has
been associated with:
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Decrements in measures of lung function (e.g.
decreases in FEV1 and FEV1/FVC)
Episodes of chronic bronchitis and chest illness in
children
Chronic pulmonary symptoms, such as bronchitis, in
adults
Particulate Matter Health Effects
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Mortality
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Several incidents, such as the Meuse Valley
disaster of 1930 and the London Smog disaster of
1952 have show an association between elevated
levels of particulate matter and mortality from
cardiovascular and pulmonary ailments
Particulate Matter Health Effects
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Mortality
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Studies such as the Harvard Six City Study and
the American Cancer Society show that exposure
to particulate matter reduced life expectancy and
this effect was predominantly associated with
PM2.5
Recent data suggest that short-term measures of
exposure, not long-term measures, are associated
with mortality
Particulate Matter Health Effects
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Cardiovascular Mortality and Morbidity
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Mortality
Changes in blood viscosity
Decreased heart rate variability
ST-segment depression
Increased discharges of implanted defibrillators
Increased blood pressure
Increased circulating markers of inflammation and
thrombosis
Particulate Matter Health Effects
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Cardiovascular Mortality and Morbidity
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Recent study by the ACS showed that increased
levels of particles strongly associated with
mortality attributable to ischemic heart disease,
dysrhythmias, heart failure, and cardiac arrest.
A 10 µg/m3 elevation in fine particulate matter
associated with an 8 – 18% increase in mortality
risk
Particulate Matter Health Effects
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Cardiovascular Mortality and Morbidity
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ACS study (continued)
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Risks were larger for smokers relative to non-smokers
Most dramatic increase in relative risk seen in
smokers with hypertension
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Suggests a possible synergistic response in particulate
matter-related cardiovascular mortality between smoking
and hypertension
Particulate Matter Health Effects
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Cardiovascular Mortality and Morbidity
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Proposed mechanisms
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Sympathetic nervous system dominance
Inflammatory events in the lung resulting in
circulating inflammatory and coagulation mediators
and subsequent endothelial injury, thrombosis, and
accelerated atherosclerosis
Direct toxic effects of particulate components on
myocardium or coronary vasculature
Particulate Matter Health Effects
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Pregnant women and their fetuses may
represent a sensitive group
Limited number of studies report an
association between exposure to high
particulate air concentrations and:
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Low birth weight
Pre-term delivery
Increase risk of infant mortality
Particulate Matter Toxicology
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Conclusions
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Abundant evidence that particulate matter causes
significant cardiovascular and pulmonary
morbidity and mortality and perhaps effects on
fetuses
These effects have been shown to occur with air
particulate levels at or near NAAQS
Removal from exposure necessary – treatment
symptomatic
Questions?
Juarez, Mexico