ComputationalComputational Model for Deposition, Model for Deposition, Clearance and Dosimetry of Inhaled Clearance and Dosimetry of Inhaled Aerosols and Radionuclides in the Aerosols and Radionuclides in the

Human Lung Human Lung

Hussain Majid

Supervisor:

Prof. Dr. Werner Hofmann

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This presentation will cover

• Background of the study

• Overview of the published work

• Conclusions

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BackgroundBackground

• The impacts of aerosols on both the natural and social environment are of particular concern because of their role in changing the Earth’s energy balance, in degrading visibility, in reducing sunlight and affecting the local climate and the humans health.

Dust Smoke

Fume Mist

Clouds Pesticides

Types Natural Aerosol

- Soil Dust- Soil Dust

- Sea Salt- Sea Salt

- Volcanic Dust- Volcanic Dust

- Oceanic Sulphates - Oceanic Sulphates Anthropogenic Aerosol

- Industrial Sulphates- Industrial Sulphates

- - Soot (Black carbon)Soot (Black carbon)

- Organic particles- Organic particles

NO HC

CO

2

CO

SO2

Aerosol

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LungLung deposition calculations-deposition calculations-ImportanceImportance

• Evaluating the efficiency of dose deliverance i.e. how much and how long will particles remain in the lung.

• Assessing toxic effects of airborne pollutant depositing in certain regions of the lung.

• Estimation for the location of potentially induced cancer due to exposure in radiation environment.

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HumanHuman LungLung

Head airway (HA)

Air is inspired through nose or mouth down to larynx and rest of the lung.

Parent Branch

Major daughter Minor daughter

Bifurcation

Tracheaobronchial (TB)

Bronchial tree is the first part of the lung. This part directs air in to the lung Each branch in the tree splits into 2 parts

Alveolar or Pulmonary (Al)

Alveoli are located at the end of the bronchial tree and is region where gas exchange occurs. 5

Lung deposition mechanismsLung deposition mechanisms

Major:• Diffusion• Sedimentation• Inertial Impaction

Minor:• Interception• Electrostatic

Naso-pharyngeal: impaction, sedimentation, electrostatic (particles > 1 μm)Tracheo-bronchial: impaction, sedimentation, diffusion (particles < 1 μm)Pulmonary:sedimentation, diffusion (particles < 0.1 μm) 6

Factors that effect Factors that effect depositiondeposition

1. Aerosol properties• Size distribution (MMD, AMD. etc)• Concentration• Particle hygroscopicity• Gas particle interaction• Chemical reaction• Particle surface charge

2. Air Flow properties• Lung capacity• Breathing frequency• Tidal Volume

3. Respiratory tract• Structure of the extrathorcic region• Lung structure and morphology• Models used: Weibel, Raabe, and Horsfield

Numbering scheme of asymmetric lung model of Raabe et al. (1974).

Particle properties

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Particle Clearance mechanismsParticle Clearance mechanisms

• Getting rid of deposited particles from the lung is called clearance

• The muco-ciliary escalator operates in the tracheobronchial region for clearance predominantly up to generation 12 and fading out at generation 16

Particle Clearance mechanisms:The Naso-pharyngeal Compartment:• mucociliary clearance (transport back to nasopharynx )• mechanical clearance (sneezing, coughing, swallowing)• absorption into circulation (soluble particles).The Tracheo-bronchial Compartment:• mucociliary clearance (transport to oropharynx)• endocytosis into peribronchial region (insoluble particles)• absorption into circulation (soluble particles)The Pulmonary Compartment:• alveolar macrophage mediated clearance• endocytosis by lung epithelial cells into interstitum• absorption into circulation (soluble particles) 8

Stochastic Lung Dosimetry Model- Stochastic Lung Dosimetry Model- IDEALIDEAL

• Deposition fractions and distribution within airways generations are modeled by the stochastic lung model-IDEAL

• Particles inhaled follow random path in the lung– Random selection of actual path out of millions of possible pathway by tracing

histories of a large number of particles

• The model uses asymmetric nature of branching pattern of the lung. – Variability of lenghts and diameter of airways are described by log-normal

frequency distributions

• Analytical (deterministic) formulas are used for computing deposition by diffusion, sedimentation and impaction

• Monte Carlo process continues even after deposition of particles within a given airway by decreasing the statistical weight of particles

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Intersubject variability of particles Intersubject variability of particles depositiondeposition

Objectives•Determine the effect of extrathoracic (ET) airway geometry on ET regional and total deposition.• Examined the effect of breathing parameters on deposition.• Investigate the joint effect of ET geometry, scaling of airway dimensions and breathing parameters on deposition.Methods• Calculation of deposition for various oral and nasal geometries by considering:

Shape factor (Sf)Minimum nasal cross-sectional area (Amin)

•Implementation of semi-empirical equations into the stochastic airway generation model IDEAL.•Intersubject variability of total deposition due to different breathing patterns was derived for 25 subjects. 10

Results• The structure of ET passages, variability of

tracheobronchial (TB) airways and alveolar dimensions and individual variations of breathing patterns exhibit significant intersubject variations.

• The variability in deposition fraction increases with the addition of influencing factors and the resulting standard deviations ranged up to 30%.

• Individual breathing habits also contribute to intersubject variability in deposition fractions and may vary up to 40%.

ConclusionMore reliable results for ET and total

deposition can be obtained with a more precise determination of nasal or oral geometry, scaling of lung dimensions and considering the individual breathing habits of the subjects.

Intersubject variability of particles Intersubject variability of particles depositiondeposition

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Intersubject variability of bronchial Intersubject variability of bronchial dosesdoses

Objectives

To apply stochastic modeling techniques to simulate the intersubject variability of biological parameters involved in radon lung dosimetry on radon progeny deposition, clearance, and resulting doses to basal and secretory cells. Methods• Estimation of effects of bronchial doses caused by intersubject variability of:

Airway morphologyBreathing parametersMucociliary clearance Thickness of bronchial epithelium

Calculation of intersubject variability of bronchial doses by :• Stochastic particle deposition model• Stochastic bronchial clearance model•Stochastic cellular dosimetry modelExposure conditions (uranium mines):• Breathing rate= 1.2 m3 h-1

•ATMD (radon progeny) = 0.8 nm (unattached ) and 375 nm (attached)12

Results• Coefficients of variations obtained due to variability in

ET and breathing parameters for unattached and attached radon progeny (averaged) are about 0.6 and 0.9, respectively.

• Due to variable airways dimensions the frequency distributions of attached radon progeny can reach high values resulting in higher deposition in few selected airways.

• The combined effect of the variability of particle deposition and mucociliary clearance velocities causes a substantial variability of the resulting retention pattern.

• The variability of the cellular doses results from the variability of surface activities and the thickness of the epithelium as a function airway diameter, and from the depth

Intersubject variability of Intersubject variability of bronchial dosesbronchial doses

Effect intersubject variations of breathing conditions on particle deposition on left side figure and the corresponding probability distribution of weighted epithelial doses (right figure).

distributions of target cellsa cross epithelial tissue.

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Dosimetry for inhaled Dosimetry for inhaled radionuclidesradionuclides

Objectives• the development of a stochastic clearance model in the alveolar region.

• the calculation of doses produced by long-lived radionuclides in alveolar and bronchial regions on the basis of the revised ICRP HRTM clearance model.

Methods• Macrophage mediated clearance from alveolar region to bronchiolar airways

• Particles escaped from thismechanism penetrate into interstitium and from there to hilar nymph nodes by slow clearance according to the rates shown in the figure below:

Particle residence times according to the updated model are calculated stochastically in the acinar region to find total disintegrations in alveolar compartments. 14

Dosimetry for inhaled Dosimetry for inhaled radionuclidesradionuclides

Results• Implementation of updated

alveolar clearance model in stochastic lung model (IDAEL) predicts 2-6 times higher doses delivered in TB region from the particles cleared from the acinar region as compared to the particles directly deposited in the TB region.

• Long lived alpha emitters in uranimum mines can deliver up to 5 percent of the doses allowed from the short lived radon daughters.

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Comparison of stochastic particle Comparison of stochastic particle lung deposition with experimental lung deposition with experimental

datadataObjectives• To compare experimental deposition measurements in different human lung

airway casts with the stochastic lung deposition model using IDEAL code.

• to investigate the effect of different deposition equations (diffusion, sedimentation and impactions) on deposition.

Methods• Deposition was calculated for the first 7 tracheobronchial (TB) airway

generations by employing different surrogate lung casts.

• To investigate the effect of different deposition equations on deposition: several analytical equations derived for the major deposition mechanisms, i.e. diffusion, sedimentation and impaction, were implemented into the IDEAL code.

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Dosimetry for inhaled Dosimetry for inhaled particlesparticlesResults

• An overall fair agreement among the deposition fractions for different cast geometries and the employed deposition equations was found.

• The variability in deposition fractions using different cast geometries arises due to structural differences of lung morphologies, derived from different ethnic and age subjects.

• The variations in the deposition fractions by the application of different deposition equations were primarily caused by the lung morphometry employed in the derivation of the equations.

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Aerosol size distribution, mass concentration Aerosol size distribution, mass concentration measurement and lung deposition calculations measurement and lung deposition calculations

for Pakistani citiesfor Pakistani citiesObjectives• To measure aerosol concentrations in terms of size, mass and particulate matter

(PM) using Grimm 1.109 portable optical Aerosol spectrometer particle counter. • To compare PM with the WHO air quality guidelines.• To analyze the crustal and trace elements.• To calculate aerosol lung deposition fractions for the measured polydisperse particle

concentrations.

Methods• Mass concentrations, as well as PM10, PM2.5, and PM1.0 concentrations, were

calculated from the particle size distributions. • Collected samples were analyzed using inductively coupled plasma atomic emission

spectrometry (ICP-AMS by Thermo Scientific, USA). • The deposition fraction was calculated for polydisperse aerosols using the stochastic

airway generation model IDEAL developed by Hofmann & Koblinger, (1990); Koblinger & Hofmann, (1990).

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Results• Maximum mass concentrations of 559 µg/m3 and

573 µg/m3 were observed in the late afternoon at about 18:30 hrs for Peshawar and Karachi (M. A. Jinnah), respectively.

• In Lahore and Rawalpindi, the peak values of 261µg/m3 and 523 µg/m3 were observed. Measurements in Lahore were carried out in residential area near sub-roads.

• The 24-h averaged PM10 and PM2.5 concentrations measured at all sampling sites are 2 to 10 times higher than the existing WHO recommendations.

Aerosol size distribution, mass concentration Aerosol size distribution, mass concentration measurement and lung deposition calculations measurement and lung deposition calculations

for Pakistani citiesfor Pakistani cities

(a)

0.E+00

5.E+09

1.E+10

2.E+10

2.E+10

dp (micrometer)

dN/d

logd

p (c

m-3

) M.A.Jinnah SUPARCOSea view LahoreRawalpindi Peshawar

(a)

0.E+00

5.E+09

1.E+10

2.E+10

2.E+10

dp (micrometer)

dN/d

logd

p (c

m-3

) M.A.Jinnah SUPARCOSea view LahoreRawalpindi Peshawar

(b)

0.E+00

2.E+06

4.E+06

6.E+06

8.E+06

1.E+07

2.75 3.25 3.75 4.50 5.75 7.00 8.00 9.25

dp (micrometer)

dN/d

logd

p(cm

-3)

0.0E+00

1.0E+082.0E+08

3.0E+08

4.0E+08

5.0E+086.0E+08

7.0E+08

dV/d

logd

p(cm

-3)

(b)

0.E+00

2.E+06

4.E+06

6.E+06

8.E+06

1.E+07

2.75 3.25 3.75 4.50 5.75 7.00 8.00 9.25

dp (micrometer)

dN/d

logd

p(cm

-3)

0.0E+00

1.0E+082.0E+08

3.0E+08

4.0E+08

5.0E+086.0E+08

7.0E+08

dV/d

logd

p(cm

-3)

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Aerosol size distribution, mass concentration Aerosol size distribution, mass concentration measurements and lung deposition measurements and lung deposition

calculations for Pakistan citiescalculations for Pakistan cities

Results• On the basis of filter analysis, it was

found that the major sources of the aerosols in these cities are from vehicular emission, industrial emissions, re-suspension of road dust and sea salt.

• ET deposition ranges from 13 to 25 % and the total deposition in the lungs ranges from 35 to 44 % for the measured particle size range.

• Deposition results revealed a significantly higher pulmonary deposition originating from urban traffic.

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ConclusionConclusion This research work was started to investigate the effect intersubject variability of extrathoracic

airways on particle deposition and the results are applied to investigate their effects on bronchial doses. The results suggest that the major sources of the intersubject variability of bronchial doses for inhaled radon progeny are the asymmetry and variability of the linear airway dimensions, the filtering efficiency of the nasal passages, and the thickness of the bronchial epithelium.

In another study, a stochastic clearance model in the alveolar region was developed and incorporated into IDEAL in order to calculate doses produced by long-lived radionuclides (LLR) and radon progeny in alveolar and bronchial regions. The results obtained by the implementation of slow alveolar clearance in to the model indicate that LLR can deliver up to 5 % of the doses in the lung predicted for the short-lived radon daughters.

In a case study, ambient aerosol data from different cities of Pakistan were collected using optical particle counter (Grimm1.109) to analyze their size distributions and mass concentration. Considering the high ambient aerosol concentrations, regional lung deposition of aerosol particles in the human respiratory tract was calculated to assess the extent of exposure to the people working in these environments. The studies for ambient aerosol data from Pakistan indicate that particulate matter (PM) concentrations at all sampling points are between 2 and 10 times higher than the maximum PM concentrations recommended by the WHO guidelines. The corresponding lung deposition calculation has revealed elevated alveolar deposition.

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