Respiratory Deposition

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Respiratory Deposition

• Jenna Sexton
• March 26, 2009

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Introduction

• Why is respiratory deposition important?
• After inhalation of an aerosol, many questions
  arise
• What was it?
• Where will it go?
• Where will it deposit?
• How long will it stay there?
• What are the health hazards?

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Respiratory deposition helps.

• Understand how and where particles deposit
• Understand possible health hazards
• What does the hazard depend on?
• Determine the effective administration of
  pharmaceutical aerosols by inhalation

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Respiratory Deposition

• Same basic mechanism as collection in a filter
• Not a fixed system at a steady flow rate
• What factors are different for deposition in the
  respiratory system?
• Added complexity
• Experimental data
• Empirically derived equations

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Respiratory System

• Three Regions
• Head airways
• Lung Airways
• Alveolar
• 23 airway branchings from trachea to alveolar
  surfaces
• Differences
• Structure
• Airflow patterns
• Function
• Retention time
• Sensitivity

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Characteristics of various regions in the
respiratory system
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Retention and Clearance of Deposited Materials

• Head and Lung Region
• Head and lung covered with layer of mucus
• Ciliary action to the pharynx
• Swallowed to GI tract
• Mucociliary escalator transports particles
  deposited in airways, out of respiratory system
  in hours

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Retention and Clearance of Deposited Particles

• Alveolar Region
• No protective mucus layer due to gas exchange
  function
• Soluble particles
• Pass through membrane into blood
• Insoluble particles
• Months to years
• Engulfed by alveolar macrophages
• Lymph nodes
• Mucociliary escalator

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Deposition

• Impaction, settling, and diffusion
• Interception and electrostatic deposition
• Deposit on contact to airway walls
• Specific mechanisms cause particles to deposit at
  different locations
• What factors affect the extent and location of
  particle deposition?

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• Impaction
• Airflow changes direction
• Particles near airway surface deposits by
  inertial impaction
• Depends on particle stopping distance at the
  airway velocity
• Typically occurs at or near first carina

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• Settling
• Most important in smaller airways and alveolar
  region
• Low velocities, small dimensions
• Ratio of settling distance to airway diameter
• Diffusion
• Brownian motion of submicrometer particles
• Ratio of root mean square displacement
• Geometric particle size
• Small diameter and long residence time favor both
  mechanisms
• Diffusion predominant for particles less than
  0.5µm

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• Which region has highest probability for
  deposition by impaction?
• Which region has highest probability for
  deposition by settling?

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• Interception
• Contacts surface due to size
• Depends on
• Proximity of gas streamline to airway surface
• Ratio of particle size to airway diameter
• Exception Long fibers
• Electrostatic
• Highly charged particles attracted to surfaces
• High number concentrations

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Total Deposition

• Experimentally determined
• Factors
• Breathing frequency
• Volume of air inhaled
• Length of pause
• For aerodynamic diameter
• Larger than 0.5 µm
• Lower breathing frequency, greater deposition.
  Why?
• Larger than 1µm
• Deposition increases with average airflow rate.
  Why?
• Long pause in breathing cycle increases
  deposition for all size ranges

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Regional Deposition

• Important to assess potential hazards
• In order to evaluate hazards, the effective dose
  at the critical site must be known
• Deposition in any respiratory region depends on
• Deposition in preceding regions
• Deposition efficiency for the region

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• Head airways
• Largest particles removed by settling and
  impaction
• Deposition increases when average inspiratory
  flow rate increases
• Lung Airways
• Flow rate greater than 20 L/min
• Impaction dominant
• Flow rate less than 20 L/min or particles 0.5-3
  µm
• Settling dominant

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• Alveolar Region
• No particles larger than 10 µm
• Settling dominant for larger particles
• Diffusion dominant for smaller particles
• Depends on size, breathing frequency, and tidal
  volume.
• Deposition reduced when lung and head airway
  deposition is increased

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Deposition Models

• International Commission on Radiological
  Protection (ICRP) and National Council on
  Radiation Protection and Measurement (NCRP)
• Developed to estimate dose to organs and tissue
  resulting in inhalation of radioactive particles

Total deposition
Where IF is inhalable fraction as used by ICRP
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• Respiratory parameters used in the ICRP model.

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• Predicted total respiratory deposition at three
  levels of exercise base on ICRP deposition model.

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Deposition Model

• The deposition fraction in the three regions can
  be approximated by these equations

DF for head airways
DF for tracheobronchial
DF for alveolar
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• Predicted total and regional deposition for light
  exercise based on ICRP deposition model.
• Dominant deposition region for particles larger
  than 1 µm?
• Dominant deposition region for particles less
  than 0.01 µm?

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Inhalability

• Efficiency of entry of particles into the nose or
  mouth
• Impact greater on particles gt3µm
• Determined experimentally
• Inhalable fraction and inhalable fraction
  sampling criterion

For U0 lt 4m/s For U0 gt 4m/s

• Where U0 is ambient velocity and da is
  aerodynamic diameter in µm.

Fewer data for nasal inhalability, but can be
approximated by
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• Predicted total respiratory deposition at three
  levels of exercise base on ICRP deposition model.

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• ACGIH (American conference of governmental
  industrial hygenists) sampling criteria for
  inhalable, thoracic, and respirable fractions

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Size Selective Sampling

• Developed due to the understanding of regional
  deposition
• Sampling a subset of the airborne particles on
  the basis of their aerodynamic size
• Subset is chosen to select those particles that
  can reach a particular region of the respiratory
  system and potentially deposit there
• Occupational health
• Inhalable
• Respirable
• Thoracic
• Ambient air quality
• PM-10
• PM-2.5

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Respirable Sampling

• Historically, used to assess occupational
  exposure to silica dust by microscopic particle
  counting
• Uses a mechanical device upstream of the sampling
  filter to aerodynamically remove those particles
  that are nonrespirable

RF(IF)(1-F(x))
Respirable Fraction
Where F(x) is simulative fraction for a
standardized normal variable x
x 2.466ln(da)-3.568
1-F(x) is the fraction of inhaled particles that
can reach the alveolar region
for x0
for xgt0
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Typical count and mass distributions for mine dust

• Why would number concentration be used instead of
  mass concentration?

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• Comparison of experimental measurements of
  alveolar deposition and ACGIH respirable fraction
  criterion.

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Thoracic Fraction

• Based on regional deposition
• Fraction of ambient aerosol particles that will
  pass beyond the larynx and reach the thorax or
  chest during inhalation
• TF(IF)(1-F(x))
• Where F(x) is the cumulative fraction for the
  standardized normal variable x
• x2.466ln(da)-6.053
• Collection efficiency
• CET(da)1-TF(da)

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• ACGIH (American conference of governmental
  industrial hygenists) sampling criteria for
  inhalable, thoracic, and respirable fractions

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PM-10

• Standard method for ambient particulate sampling
• Closely related to thoracic fraction
• Similarities
• Same cutoff size of 10 µm
• Based on particles that penetrate to the thorax
• Differences
• PM-10 is a fraction of the total ambient
  particulate
• Cutoff curve that defines PM-10 is sharper
• Fraction of particles included in PM-10 fraction
  can be estimated by

for dalt1.5micron
for 1.5ltdalt15micro
for dagt15micron
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PM-2.5

• Developed because of health effects from fine
  particles
• EPA adopted new standards for sampling fine
  particles
• The fraction of particles that are included in
  the PM-2.5 fraction can be determined by

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Overview

• Respiratory System
• Deposition Mechanisms
• Deposition Model
• Inhalability
• Particle Size Selective Sampling
• Thoracic Fraction