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Effect of intersubject variability of extrathoracic

airways on particle deposition

Hussain MajidPh.D Scholar

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Introduction• The ET (nasal and oral) airways are the first route

and serve as a filter for the inhaled particles. • The ET airways are the important determinant of

doses delivered by inhaled particles to the lung. • Since the structure of the ET airway geometry

exhibit significant intersubject variations, it affects both extrathoracic deposition and in further consequence, the fraction of inhaled particles reaching the lung.

• The current study is focused on the effect of inter-subject variability of ET airways on particle deposition.

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Morphmetry of ET region

ET region can be subdivided into following regions• Nasal Cavity• Oral Cavity• Turbinate region• Nasopharynx• Oropharynx • Hypopharynx• Larynx

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Nasal Intersubject Variability

• Nasal dimentions and particle deposition vary significantly among individuals

• Nasal airway dimensions measured by K.H. Cheng et al. (1996) using MRI technique in 10 adults male were used in the current study to determine nasal and total deposition

Tomographic pictures of nasal cross-sectional geometry by Montgomery et al. (1979)

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Important Parameters Affecting Nasal Deposition

• Shape Factor (Sf)– Measure of the complexity of the airway dimensions– It is the ratio of the airway perimeter to a reference perimeter or a

normalized surface area

– Larger values of Sf result in a higher intensitiy of turbulences which creates more secondary flows and increases probability of particle deosition

• Minimun Cross-Sectional Area (Amin)– Minimum cross-sectional area is the characteristic nasal airway

dimension measured in units of cm2.

– Smaller values of Amin found to be associated with increased probability of particle deposition

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Oral Intersubject Variability

• Oral dimentsions and particle deposition vary significantly among individuals

• Oral airway dimensions measured by B.Grgic at al. (2004) using MRI technique in 5 adults male were used in the current study to determine oral and total deposition

Oral cross-sectional geometry by T.R Sosnowski et al. (2006)

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Equivalent Diameter (L) Affecting Oral Deposition

• It is the equivalent diameter of the average cross sectional area of the oropharyngeal airway

• Smaller values of ´L´ are found to be associated with increased probability of particle deposition

Darker regions correspond to more deposition

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Effects of Intersubject Variability• Enhanced disturbance in air flow structure

(enhanced turbulance, secondary flow)• Aerosol filtration as well as penetration efficiency

varies with biological variability in ETairway• Deposition efficiency depends upon geometric

parameters of ET passage• Regional and total lung deposition efficiency

varies with the biological variabilty of ET airway passages

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Deposition Regimes• Depending on particle size and its deposition

efficiency, two deposition regimes can be defined

1. Diffusion deposition regime2. Impaction deposition regime

• Diffusion deposition regime– For particle size ≤0.2 µm, diffusion deposition is

dominant and hence classified as diffusion deposition regime

– Diffusion deposition is primarily dependent on diffusion coefficient (D) and flow rate (Q)

– Nasal deposition efficiency is fitted by the equation

)355.0exp(1 28.05.014.4 QDSE fn

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Deposition Regimes (cont...)

• Impaction regime– For particle size >0.2 µm, impaction deposition is

dominant and classified as impaction deposition regime

– Impaction deposition is primarily dependent on aerodynamic diameter (da) and flow rate (Q)

– Nasal Impaction deposition is approximated by the equation

where is the dimensionless Stokes number

)110exp(1 StkEn )18/( 5.1

min25.0 AQdStk a

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Deposition Regimes (cont...)

– Oral Impaction deposition is approximated by the equation

where is the dimentionless stokes number

) 2.19exp(1 StkEo )9/( 2 LUdStk a

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Method for deposition calculations

• For calculation of extrathoracic, regional and total deposition, semi-empirical equations were implemented into the Monte Carlo deposition code IDEAL (Hofmann & Koblinger, 1990)

• Unit density monodisperse particles in the size range of 0.001-10 µm were used under sitting and light exercise breathing conditions.

• Uniform breathing with equal inspiration and expiration and zero breath hold time was assumed at a fixed value of functional residual capacity (FRC) of 3300 ml in the lung

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Method for deposition calculations (Contd..)

• Total and regional particle deposition was calculated by stochastic airway generation model IDEAL (Hofmann & Koblinger 1990)

• Results for both regimes were combined in one diagram for whole particle size range

• The obtained results were then compared with some other semi-empirical equations derived so far for calculation of deposition fractions

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Method for deposition calculations (Contd..)

Other formulas used for calculations

Nasal deposition

124 1)(100.31 QdE an

By ICRP (1996)

By NCRP (1997)

94.02

46001/1

QdEni

01.12

23001/1

QdEne

125.05.018exp1 QDEn da ≤0.2 µm

da >0.2 µm

da >0.2 µm

125.05.08.12exp1 QDEni

125.05.00.15exp1 QDEne

da ≤0.2 µm

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Method for deposition calculations (Contd..)

Other formulas used for calculations

Nasal deposition

6/12/112/14/1 83.453.1 ScSc

By Zongqin Zhang and G. Yue in 2003

)6.1600309.0exp(1 28.05.02 QDdE an

Cheng et. al. 2003

Asgharian et al. (2004)

58.02975.061.24 DQ

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Method for deposition calculations (Contd..)

Other formulas used for calculations

Oral deposition

By ICRP (1996)

By NCRP (1997)

da ≤0.2 µm

da >0.2 µm

da >0.2 µm

125.05.03.10exp1 QDEmi

125.05.051.8exp1 QDEme

da ≤0.2 µm

14.12.06.024 )(101.111 Tam VQdE

125.05.09exp1 QDEm

37.12

000,301

1

Qd

E

)4.20000278.0exp(1 31..066..02 QDdE aoCheng et. al. 2003

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Results

• The simulated effects of intersubject variability of ET airway on nasal, oral and total deposition are presented here in the following figures

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Effect of intersubject variability expressed in the form of coefficient of variation (CV) on nasal oral and total deposition for different particle size under sitting, light exercise conditions

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Summary of results• For nasal deposition larger values of Sf and smaller values of

Amin cause higher deposition efficiency.

• Larger values of Sf a is measure of larger complexity which increases turbulences in flow and cause secondary flows and hence increases the probability of particle deposition.

• Small values of Amin which is variable during breathing cycle is a hindrance to smooth flow and hence increases the deposition probability.

• At very low and high flow rates deposition efficiency for 1 nm and 10 µm particles approach 100 percent in nasal airways.

• The penetration efficiency and hence deposition in the downstream airway generations is also different for all subjects especially for ultra fine particles.

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Summary of results (contd…)• For oral deposition in the impaction regime smaller values

of L cause higher deposition efficiency. • The trend for higher deposition efficiency for smaller value

of L can also be observed with an increase in flow rate. • This higher deposition for smaller values of the equivalent

diameter is due to increases in turbulences caused by the narrow parts of the oral passages.

• At very low and high flow rates deposition efficiency for 1 nm and 10 µm particles is highest.

• The penetration efficiency in downstream airway generations for oral breathing in all subjects doesn’t show variability except for an idealized mouth.

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Conclusions

• The range of the experimentally observed deposition efficiencies could be approximated by 2 standard deviations of Sf , Amin and L values.

• Thus, it was assumed that intersubject variations of the ET deposition are determined primarily by corresponding fluctuations of Sf , Amin and L values.

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Dankeschön