Modeling Deposition of Inhaled Particles - Aerosols: Measurement, Dosimetry, and Health Effects - page 84

5.4.6 Clearance .................................................................................................................... 98
5.4.6.1 Mucociliary Clearance ................................................................................ 98
5.4.6.2 Macrophage Clearance or Phagocytosis .................................................... 101
5.4.6.3 Free Particle Uptake and Translocation to the Interstitium ....................... 102
5.4.6.4 Importance of Clearance in Particle Deposition Modeling ....................... 102
5.4.7 Disease...................................................................................................................... 102
5.4.7.1 Chronic Obstructive Pulmonary Disease .................................................. 102
5.4.7.2 Asthma ....................................................................................................... 103
5.4.7.3 Cystic Fibrosis............................................................................................ 103
5.4.7.4 Effect of Obstructive Disease on Particle Deposition and Distribution...... 103
5.4.7.5 Modeling Disease ...................................................................................... 103
5.4.8 Age............................................................................................................................ 104
5.5 Theory and Experiment........................................................................................................ 104
5.5.1 Predictions of Particle Deposition ............................................................................ 104
5.5.2 Particle Deposition Measurements ........................................................................... 104
5.5.2.1 Casts and Models ....................................................................................... 104
5.5.2.2 Deposition Patterns Deduced from Clearance Studies.............................. 107
5.5.2.3 Light-Scattering Methods .......................................................................... 107
5.5.2.4 Imaging Studies ......................................................................................... 107
5.5.2.5 Microdosimetry ......................................................................................... 107
5.5.3 Comparison of Modeling and Data .......................................................................... 109
5.5.3.1 Simulations of Total Particle Deposition ................................................... 110
5.5.3.2 Simulations of Compartmental Particle Deposition .................................. 110
5.5.3.3 Simulations of Particle Distribution Generation-by-Generation ............... 112
5.5.3.4 Simulations of Local Particle Deposition .................................................. 112
5.6 Applications of Deposition Models ...................................................................................... 114
5.6.1 Exposure and Risk Assessment ................................................................................ 114
5.6.2 Design of Inhaled Pharmaceuticals and Delivery Systems ...................................... 115
5.7 Summary .............................................................................................................................. 115
Acknowledgment ........................................................................................................................... 115
References...................................................................................................................................... 116
5.1 INTRODUCTION
The mathematical modeling of the deposition and distribution of inhaled aerosols within human
lungs is an invaluable tool in predicting both the health risks associated with inhaled environmental
aerosols and the therapeutic dose delivered by inhaled pharmacological drugs. However, mathemati-
cal modeling of aerosol deposition requires knowledge of the intricate geometry of the respiratory
network and the resulting complex motion of air and particles within the airways. In this chapter,
an overview of the basic engineering theory and respiratory morphology required for deposition
modeling is covered. Furthermore, current deposition modeling approaches are reviewed, and many
factors affecting deposition are discussed. Experimental methods for measuring lung deposition are
presented, albeit briely, and the comparison between experimental results and modeling predictions
is examined for a selection of modeling efforts.
5.2 FLUID DYNAMICS IN AIRWAYS
The deposition patterns associated with inhaled particulate matter are intrinsically linked to the
airlow patterns within the respiratory system. Therefore, any effort to realistically model particle
deposition requires an understanding of the fundamental luid dynamics theory behind the motion
of air in the extrathoracic and lung airways.