Particulate Matter Toxicology by pengxiang

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									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
   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)
   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)
   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)
   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)
   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)
   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)
   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
   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
   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
   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
   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
   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
   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
   Classification
   Existing air standards
   Dose considerations
   Deposition and clearance in lung
   Health effects
Particulate Matter - Regulatory
Classification
   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
   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
   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
   Area samples
       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
   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
   Personal samples
       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
   Many measures of dose
       Exposure dose (De)
       Inhaled dose (Di)
       Total deposited dose (Dd)
       Regional deposited dose (Dr)
       Dose deposited per regional surface area (Drsa)
Dose Determinations
   Various dose matrices differ in the amount of
    information considered
       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
   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
   Physical activity
   Impaired clearance
   Proximity to source
   Behavioral changes, such as curtailing
    physical activity outdoors, remaining in air-
    conditioned environments, use of air filters
    can lower one’s dose.
Particulate Matter Deposition
   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
   5 – 30 µm particles deposited in nasopharynx
    by inertial impaction
       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
   1 – 5 µm particles deposited in the
    bronchiolar region via sedimentation
       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
   Factors affecting deposition include:
       Inactivity (periods of quiet breathing)
       Physical activity
       Breath holding
       Pulmonary disease (e.g. chronic bronchitis)
       Irritants (e.g. tobacco smoke)
Particulate Matter Clearance
   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
   Particles removed from the respiratory system
    may be transported
       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
   Nasal Clearance
       Anterior portion- wiping or blowing
       Other portions – mucociliary transport
           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
   Tracheobronchial Clearance
       Mucociliary escalator transports particles and
        particle-laden macrophages to the oropharynx
        where they are swallowed
           Relatively rapid and complete within 24-48 hours
       Infection and other injuries can greatly impair
        clearance from this area
Particulate Matter Clearance
   Pulmonary Clearance
       Several mechanisms:
           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
   Uptake and transport via sensory neuronal
    axons
       Area of intense research
       Supported by research in laboratory animals
        using dye particles, polio virus particles, and 14C-
        ultrafine particles
       Concern entails direct entry of potentially toxic
        substances into the CNS
Particulate Matter Health Effects
   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
   Asthma
       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
   Asthma
       Mechanism of exacerbation not fully elucidated
       Possibly mediated by particulate matter-induced
        inflammation
           Direct injury
           Activation of cellular hose defense pathways leading
            to inflammation
Particulate Matter Health Effects
   Asthma
       Support for inflammatory hypothesis
           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
   Asthma
       Asthmatics considered at risk for exacerbation
        due to ambient particulate matter because
           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
   COPD
       Perhaps mediated via inflammatory processes
           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
   Other Respiratory Ailments
       Long-term exposure to particulate matter has
        been associated with:
           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
   Mortality
       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
   Mortality
       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
   Cardiovascular Mortality and Morbidity
       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
   Cardiovascular Mortality and Morbidity
       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
   Cardiovascular Mortality and Morbidity
       ACS study (continued)
           Risks were larger for smokers relative to non-smokers
           Most dramatic increase in relative risk seen in
            smokers with hypertension
               Suggests a possible synergistic response in particulate
                matter-related cardiovascular mortality between smoking
                and hypertension
Particulate Matter Health Effects
   Cardiovascular Mortality and Morbidity
       Proposed mechanisms
           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
   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:
       Low birth weight
       Pre-term delivery
       Increase risk of infant mortality
Particulate Matter Toxicology
   Conclusions
       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

								
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