Particle Deposition in Human Lung Airways: Effects of Airflow, Particle Size, and Mechanisms

Characterizing particle deposition in the airways of the human lungs is essential to evaluate the health effects of particulate air pollution. However, lung deposition is rather complicated, and its main influencing factors remain unclear. Hence, this study applied computational fluid dynamics (CFD) to investigate the roles of airflow (Reynolds number [Re] = 100–2000) and particle size (1–10 μm) in deposition using a human tracheobronchial airway model (G3–G6). We calculated the deposition efficiency (DE) based on two mechanisms, inertial impaction (DEi) and gravitational sedimentation (DEg), which produced hot spots around the bifurcations and uniform distributions along the tube, respectively. Furthermore, as the particle size increased, DEi grew rapidly, whereas DEg grew log-linearly. Particles that were less than 2 μm in diameterμ only penetrated deep in the lungs where the airflow rate was low, but 3 μm particles were more likely to settle in this region owing to the combination of gravitational sedimentation and inertial impaction. Larger particles, on the other hand, mainly deposited in the proximal bifurcations as a result of inertial impaction. Additionally, the deposition due to inertial impaction and that due to gravitational sedimentation primarily depended on the Stokes number (St) and the ratio of St to Re , respectively. The orientation of the human body was another potential factor in the pattern of deposition, although the upright and lateral positions exhibited similar deposition efficiencies for 3 μm particles regardless of Re. These findings identify the critical Reynolds number at which the particle deposition mechanism for a specific size shifts from gravitation to inertia.


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A predictive understanding of particle transport through bifurcating airways is 36 essential either to optimize therapeutic effects of pharmaceutical aerosols or to minimize 37 harmful effects of toxic aerosol exposure (Patton and Byron, 2007;Finlay and Martin, 38 2008; Lo ndahl et al., 2017; Deng et al., 2018). However, particle deposition in human lung 39 is rather complicated (Deng et al., 2019). The mechanism of specific diameter particle 40 deposition in the designated human lung regions still remains unclear. 41 Particle deposition in human airways is a rather complicated process, and affected by 42 many factors. These factors include particle size and shape, breathing rate, lung volume, Sznitman, 2015). However, the contributions of different mechanisms to particle 50 deposition in airways vary with particle sizes and airflow rates. Therefore, it is important 51 to identify the roles of particle size, airflow, and the mechanisms in the particle deposition 52 in human airways. 53 Numerous studies have investigated the effects of mechanisms on particle deposition 54 in human lung airways. Hoffmann and colleagues demonstrated that gravitational settling 55 may occur in peripheral airway bifurcations where both impaction and diffusion are not 56 significant (Hofmann et al., 1995). Comer and coworkers found that inertial impaction is 57 important for micron-size particle deposition (Comer et al., 1999). Zhang and coauthors 58 concluded that micron-size particle deposition occurred mainly along the carinal ridges 59

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4 due to inertial impaction in a triple bifurcating airway model (G3 -G6) . 60 Zhang and coauthors conducted another work by computing the micron-size particle Bala sha zy (2008) stressed that the deposition patterns were very sensitive to the particle 65 size, and that particles larger than 1μm were mainly deposited due to impaction in the 66 airway generations G0-G4. Kleinstreuer et al. (2007) found that both inertial impaction 67 and gravitational sedimentation were significant mechanisms in the medium-size 68 bronchial bifurcations (G6-G9). Martonen et al. (2002) pointed out that particle 69 deposition due to inertial impaction and sedimentation were nonlinear functions of 70 particle diameters in the human upper respiratory airway model. Therefore, the role of 71 particle size and airflow in the deposition mechanism still remains uncertain.

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The present study mainly focused on the particle size, airflow patterns and 73 mechanisms of particle deposition in a three-dimensional G3-G6 airway model. Using 74 computational fluid dynamics (CFD), this work predicted the distribution of inhalable 75 particles in different sizes delivered to the lung airways. Besides the particle diameter, the 76 authors also considered various inhaling flow rates in an attempt to identify the 77 mechanisms which affect the particle transport in the human lung airways.

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Airway geometry 80 The human tracheobronchial tree is composed of a system of dichotomous tubular 81 bifurcations (Horsfield and Thurlbeck, 1981 laminar flow in the rigid airways, the Navier-Stokes equations were given as follows: where and p are the velocity vector and pressure, respectively. All these variables are where * , * and g are the particle displacement, the particle velocity and the 124 gravitational acceleration, respectively, and f D represents the drag force coefficient per 125 unit particle mass given by: where ρ p = 2000 kg/m 3 and d p are respectively the particle density and diameter, CD 128 is the drag force coefficient (Haider and Levenspiel, 1989; Morsi and Alexander, 2006).

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The particle Reynolds number Re p is defined as: S t is the Stokes number, and defined as: where C c is the Cunningham correction factor.

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Boundary conditions 135 Uniform velocity profiles were applied at the inlet cross-section. Pressure-outlet 136 boundary condition was adopted at the outlets. Non-slip boundary condition was 137 employed along the airway walls.

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In order to complete the particle transport formulations, the uniform-uniform inlet 139 particle profile, according to Zhang and Kleinstreuer (2001), was adopted with the initial 140 velocity of the corresponding airflow velocity. For all the walls, the trap condition was 141 applied with the assumption that particles were trapped as soon as they touch the wall 142 surfaces. Escape condition was applied to the inlet and outlets. work. The results showed that the medium and fine grid arrangements can predict the 165 axial velocity well with little discrepancy. Therefore, the medium grid arrangement for the 166 symmetric geometry was selected to fulfill the subsequent validation and investigation.

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The QUICK scheme was used to discretize the nonlinear convection terms in the 168 Navier-Stokes equation, which ensured an upwind character and high order accuracy.

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The segregated implicit approach was used to ensure a fast convergence and low memory The discrete phase model (DPM) was used to calculate the particle trajectories after 176

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9 the steady airflow was achieved. To ensure independence from the number of particles 177 released, different magnitudes were considered, and no significant change was found in 178 deposition when the number was larger than 10,000 for all the cases considered. 6(a)) while DEg increases log-linearly with particle size (Fig. 6(b)). On the other hand, the 218 effect of Re is different. DEi increases rapidly with Re while DEg decreases; DEi+g appears 219 similar with DEg when Re≤200, and similar with DEi when Re ⩾ 500 and dp ⩾ 3 μm ( Fig.   220 6(c)). Hence in the subsequent sections, we will investigate the deposition patterns for 1, balance between gravity and inertia can be found: there is a "U" shape DEi+g curve for 3μm 236 particles. Firstly, the particle deposition efficiency decreases rapidly with the increasing 237 Reynolds numbers when the gravitational sedimentation dominates. Then, it keeps nearly 238 constant due to the balance between inertial impaction and gravitational sedimentation.

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Finally, the DEi+g curve rapidly increases with Re. For large particles (dp = 5, 10 μm), the 240 curve of DEi+g is like a right-hand of "U" shape as inertial impaction dominates even at low 241 Reynolds numbers. 242 Fig. 9 shows the 2-D views of particle deposition patterns due to different 243 mechanisms under four Reynolds numbers. As particles deposit symmetrically at the first 244 carina due to the symmetric airway, half of the airway model for each case separated by 245 the x = 0 plane is displayed. As the deposition efficiency of 1 μm and 3 μm particles is too 246 low (< 1% for dp=1 (Fig.8a), and<7% for 3 μm (Fig.8b), the 2-D views of their deposition 247 patterns are not shown here. Only cases of dp = 5 μm and dp = 10 μm are illustrated. As

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12 indicates that inertial impaction is not effective yet at Re=100. While for the combined 250 mechanism (the right halves of panel (a)), particles distribute uniformly along the inside 251 wall of tubes without hot spots for both particle diameters due to gravitational 252 sedimentation. When Re rises, the effects of gravitational sedimentation decease, while 253 the inertial impaction becomes more and more effective, and significant hot spots can be  Fig. 10(a), changing the body orientation can lead to 264 different deposition patterns for both small (dp = 3 μm) and large (dp = 10 μm) particles.

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This study was to predict the effect of particle size and airflow rate and the

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13 contribution of different mechanisms to particle deposition in a triple-bifurcation airway 275 model. It is found that the particles in different size can be deposited due to different 276 mechanism.

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The present work used the three-dimensional in-plane triple-bifurcation airway

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The airflow structure was found to significantly affect the particle deposition

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14 The strength of this study lies in the fact that the authors have separated the role of 300 different mechanism of deposition in the airway model. The deposition mechanism is one 301 of the factors that determined the particle deposition patterns in the human airways 302 (Hofmann, 2011). Particles deposit in the lung mainly due to the following three 303 mechanisms: inertial impaction, gravitational sedimentation and Brownian diffusion.

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Previous studies have already demonstrated that particles can deposit due to different 1500 for dp = 3 μm) to low (Recritical = 300 for dp = 10 μm) with the increasing particle size.

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It meant that inertial impaction for larger particles would dominate at lower Reynolds 316 number. Consequently, the bigger the particles are, the more burden of the proximal 317 bifurcation will have.

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The other strength of the study is that the authors established the relationships 319 between non-dimensional parameters and DEi as well as DEg, respectively. Firstly, It was direction on the 1-3 μm particle deposition in pulmonary acinus during breath holding.

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They found that gravitational direction had no effect on the total deposition fraction, but (1 ≤ dp ≤ 10 μm) particle deposition in the G3-G6 airway model, and detailed information 362 about deposition mechanisms. It concluded that particle size and inhalation rates 363 determined the deposition site, quantity and mechanism. Particles mainly deposit at the 364 inner wall of the tubes that experience higher axial flow rate and stronger inward 365 secondary velocity. Particles smaller than 3 μm cannot deposit in G3-G6 airways due to 366 either inertial impaction or gravitational sedimentation. The critical value above which 367 the inertial impaction took over the dominant deposition mechanism would shift from 368 high to low with the increasing particle size. Therefore, for larger particles (dp > 3 μm), 369 inertial impaction rather than gravitational sedimentation would take over the dominant 370 mechanism at lower Reynolds number, and they can be mainly deposited in the proximal and Re 2 . The findings provide a precise Reynolds number when the deposition mechanism 376 of a certain size particle shifts from gravitation to inertia.

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24 Figure 4. Axial and secondary velocity distributions and particle deposition pattern for Re=1000 and dp=10μm.

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28 (a) dp = 1 μm (b) dp = 3 μm (c) dp = 5 μm (d) dp = 10 μm