**3. Case studies**

Employing the advanced CFPD models for unconventional aerosol particle dynamics discussed in Section 2.4, two case studies are briefly shown in this section: (a) the transport and deposition of ellipsoidal fiber as a new pulmonary drug carrier in a subject-specific human upper airway model and (b) the transport, hygroscopic behavior, and deposition of multicomponent electronic cigarette (EC) droplets in an idealized triple bifurcation unit (TBU).

#### **3.1. Transport and deposition of ellipsoidal fibers in a human upper airway**

Due to the toxicity of airborne ellipsoidal fibers to human and hence the lack of experimental data using human volunteers because of the severe ethical constraints, it is essential to numerically investigate the transport and deposition of fibers in human respiratory systems. On the other hand, multifunctional micron fibers are also being used as pulmonary drug carriers for disease treatment. Therefore, the numerical investigations will provide data for estimations of dosimetry, safety, and the efficacy of drugs in the lungs which are also critical factors in the development of inhaled medicines.

**Figure 7.** Ellipsoidal fiber translational and rotational motion in Poiseuille flow (Reave = 173) (reprinted from [10]): (a) ellipsoidal fiber long-axis directions released at an off-center position *y*\* = −5/6, *z*\* = 0; (b) ellipsoidal fiber long-axis directions released at center *y*\* = 0, *z*\* = 0; (c) *y*-direction velocities of fibers with the same volume and different aspect ratios; (d) trajectories for fibers with the same volume and different aspect ratios.

Considering the significant impact the anisotropic shape has on the accuracy of trajectory prediction, the one-way coupled EL-ER method discussed in Section 2.2.4.1 was employed [10] to calculate the translational and rotational motion of submicron ellipsoidal fibers of different aspect ratios (1 < *β* < 20). Brownian motion was also considered in both Poiseuille flow (see **Figure 7(a)**–**(d)**) and complex flows inside a subject-specific human upper airway (see **Figure 8**).

**3. Case studies**

64 Aerosols - Science and Case Studies

Employing the advanced CFPD models for unconventional aerosol particle dynamics discussed in Section 2.4, two case studies are briefly shown in this section: (a) the transport and deposition of ellipsoidal fiber as a new pulmonary drug carrier in a subject-specific human upper airway model and (b) the transport, hygroscopic behavior, and deposition of multicomponent electronic cigarette (EC) droplets in an idealized triple bifurcation unit (TBU).

Due to the toxicity of airborne ellipsoidal fibers to human and hence the lack of experimental data using human volunteers because of the severe ethical constraints, it is essential to numerically investigate the transport and deposition of fibers in human respiratory systems. On the other hand, multifunctional micron fibers are also being used as pulmonary drug carriers for disease treatment. Therefore, the numerical investigations will provide data for estimations of dosimetry, safety, and the efficacy of drugs in the lungs which are also critical

**Figure 7.** Ellipsoidal fiber translational and rotational motion in Poiseuille flow (Reave = 173) (reprinted from [10]): (a) ellipsoidal fiber long-axis directions released at an off-center position *y*\* = −5/6, *z*\* = 0; (b) ellipsoidal fiber long-axis directions released at center *y*\* = 0, *z*\* = 0; (c) *y*-direction velocities of fibers with the same volume and different aspect

Considering the significant impact the anisotropic shape has on the accuracy of trajectory prediction, the one-way coupled EL-ER method discussed in Section 2.2.4.1 was employed [10] to calculate the translational and rotational motion of submicron ellipsoidal fibers of different aspect ratios (1 < *β* < 20). Brownian motion was also considered in both Poiseuille flow (see

ratios; (d) trajectories for fibers with the same volume and different aspect ratios.

**3.1. Transport and deposition of ellipsoidal fibers in a human upper airway**

factors in the development of inhaled medicines.

To gain basic insight for ellipsoidal particle dynamics, Poiseuille flow with an averaged Reynolds number of Reave = 173 is considered where ellipsoidal fibers with randomly initialized incidence angles were released at different inlet-plane positions, their trajectories computed and visualized (see **Figure 7(a)**–**(d)**). **Figure 7(a)** and **(b)** show the rotational/translational motion of the ellipsoidal fibers (*β* = 14 and *ap* = 0.5 μm) released at two locations, i.e., off-center and center. Released at an off-center position (see **Figure 7(a)**), the coupling of rotation and translation of the ellipsoidal particle can be clearly observed with periodical sudden turns of 180° in a "clockwise" manner. Released at the center (see **Figure 7(b)**), the flow velocity gradients were zero, i.e., no torques were affecting the particle. As a result, the particle kept its initial orientation till it reached a location where the velocity gradients and resulting torques were sufficiently large to rotate the particle. The frequency of the sudden rotation is influenced by the stability of the fibers at different locations of the flow field. It must be noted that using conventional CFPD models for spherical particles, the rotational motion is neglected and not able to be visualized.

**Figure 8.** Total deposition efficiencies of ellipsoidal fibers, including spheres (*β* = 1.0, at two inhalation flow rates (*Q*in = 15 L/min and 60 L/min) in a subject-specific human upper airway model as a function of aspect ratio.

Parametric sensitivity analyses were also performed for the aspect ratio effect on the translational and rotational motion for ellipsoidal fibers with the same equivalent volume diameter (see **Figure 7(c)** and **(d)**). Specifically, **Figure 7(c)** shows different *y*-direction velocities of fibers with the same volume but different aspect ratios. With the increase in aspect ratio *β*, the *y*direction sedimentation velocity decreases and the rotation frequency of the fibers decreases. Indeed, with different aspect ratios, the Stokes resistance correction factors in the three principal directions of the ellipsoidal particle are all changing, which leads to the variation of the sedimentation velocity in *y*-direction. **Figure 7(d)** provides different trajectories of particles with the same volume and different aspect ratios. Particles with larger *β*-values have a stronger tendency to follow the mainstream and hence travel farther than a particle with a smaller *β*. Therefore, it can be conjectured that fibers are more likely to migrate deeper into the lung airways when compared to spherical particles of the same volume. In other words, when quasialigned to the flow, a fiber experiences a larger drag force in the gravitational direction (i.e., *y*-direction), so that particles with larger aspect ratios may not deposit in parallel flow.

To further investigate the transport characteristics of ellipsoidal fibers with different aspect ratios and the same volume, parametric studies on fiber transport in a subject-specific human upper airway with 20-mm inlet are performed. Specifically, a comparison of total deposition efficiencies of spheres and ellipsoidal fibers for two inhalation flow rates is shown in **Figure 8**. The total deposition data indicate that slender toxic ellipsoidal fibers (i.e., those with higher aspect ratios) are potentially more harmful than thicker ones due to their ability to penetrate into deeper lung regions when somewhat aligned with the mainstream flow. In contrast, to treat deeper lung diseases using pulmonary drugs, slender ellipsoidal fibers as drug carriers may enhance the drug delivery efficacy compared to conventional spherical ones.

#### **3.2. Size change dynamics of multicomponent droplets in a G3-G6 TBU**

As tobacco-smoking is addictive with potentially detrimental effects and hence related to high health-care cost, alternatives such as electronic cigarettes (ECs) have been developed. EC aerosols consist of multicomponent droplets and vapors, e.g., water, nicotine, glycerol, and PG. Although ECs can look like and ultimately should "taste" like conventional cigarettes, their design and function as well as product quality are very different. Debates are still going on for the use of ECs, with reported positive and negative aspects of EC consumptions [4]. Therefore, investigations on the differences between conventional cigarette smoke and EC aerosols are of great interest for EC product design as well as government regulations.

In this study, as the first step, the focus is on hygroscopic growth of nanosize multicomponent droplets and droplet-vapor interactions during transport with subsequent deposition in a triple bifurcating unit (TBU) representing G3–G6 lung airway (see **Figure 9**). Using the MCM-DD model derived in Section 2.2.4.2, electronic cigarette (EC) droplets with different compositions were compared with conventional smoke particles (CSPs) as well as solid particles on their different behaviors of evaporation/condensation dynamics during their transport and deposition in the TBU, with body temperature *T* = 310.15 K and relative humidity RH = 99.5% [2].

**Figure 10(a)** shows the comparisons of hygroscopic behavior between three EC droplets with different compositions and two conventional cigarette smoke particles (CSPs) with different compositions (see **Table 1** for compositions). At RH = 99.5%, both EC-droplets and CSPs grow due to condensation effect. However, CSPs #1 and #2 grow less than EC-droplets #B1 to #B3. This suggests that with initial droplet diameter and ambient environment (humidity) being the same, EC-droplets #B1 to #B3 will be always larger in size than the liquid CSPs #1 and #2. Further, these EC-droplets with larger diameters with have higher inertia, and thus being less affected by the local airflow structure than CSPs.

Computational Fluid-Particle Dynamics Modeling for Unconventional Inhaled Aerosols in Human Respiratory Systems http://dx.doi.org/10.5772/65361 67

tendency to follow the mainstream and hence travel farther than a particle with a smaller *β*. Therefore, it can be conjectured that fibers are more likely to migrate deeper into the lung airways when compared to spherical particles of the same volume. In other words, when quasialigned to the flow, a fiber experiences a larger drag force in the gravitational direction (i.e., *y*-direction), so that particles with larger aspect ratios may not deposit in parallel flow.

To further investigate the transport characteristics of ellipsoidal fibers with different aspect ratios and the same volume, parametric studies on fiber transport in a subject-specific human upper airway with 20-mm inlet are performed. Specifically, a comparison of total deposition efficiencies of spheres and ellipsoidal fibers for two inhalation flow rates is shown in **Figure 8**. The total deposition data indicate that slender toxic ellipsoidal fibers (i.e., those with higher aspect ratios) are potentially more harmful than thicker ones due to their ability to penetrate into deeper lung regions when somewhat aligned with the mainstream flow. In contrast, to treat deeper lung diseases using pulmonary drugs, slender ellipsoidal fibers as drug carriers

As tobacco-smoking is addictive with potentially detrimental effects and hence related to high health-care cost, alternatives such as electronic cigarettes (ECs) have been developed. EC aerosols consist of multicomponent droplets and vapors, e.g., water, nicotine, glycerol, and PG. Although ECs can look like and ultimately should "taste" like conventional cigarettes, their design and function as well as product quality are very different. Debates are still going on for the use of ECs, with reported positive and negative aspects of EC consumptions [4]. Therefore, investigations on the differences between conventional cigarette smoke and EC aerosols are of great interest for EC product design as well as government regulations.

In this study, as the first step, the focus is on hygroscopic growth of nanosize multicomponent droplets and droplet-vapor interactions during transport with subsequent deposition in a triple bifurcating unit (TBU) representing G3–G6 lung airway (see **Figure 9**). Using the MCM-DD model derived in Section 2.2.4.2, electronic cigarette (EC) droplets with different compositions were compared with conventional smoke particles (CSPs) as well as solid particles on their different behaviors of evaporation/condensation dynamics during their transport and deposition in the TBU, with body temperature *T* = 310.15 K and relative

**Figure 10(a)** shows the comparisons of hygroscopic behavior between three EC droplets with different compositions and two conventional cigarette smoke particles (CSPs) with different compositions (see **Table 1** for compositions). At RH = 99.5%, both EC-droplets and CSPs grow due to condensation effect. However, CSPs #1 and #2 grow less than EC-droplets #B1 to #B3. This suggests that with initial droplet diameter and ambient environment (humidity) being the same, EC-droplets #B1 to #B3 will be always larger in size than the liquid CSPs #1 and #2. Further, these EC-droplets with larger diameters with have higher inertia, and thus being less

may enhance the drug delivery efficacy compared to conventional spherical ones.

**3.2. Size change dynamics of multicomponent droplets in a G3-G6 TBU**

humidity RH = 99.5% [2].

66 Aerosols - Science and Case Studies

affected by the local airflow structure than CSPs.

**Figure 9.** G3–G6 triple bifurcation unit (TBU) with hexahedral mesh and airflow velocity contour for Rein = 61.

**Figure 10.** (a) Droplet diameter growth ratio comparisons between CSPs and EC-droplets; (b) total deposition efficiency of EC-droplet #B2, CSPs #1 and solid particles with different initial diameters (reprinted from [2]).


**Table 1.** Composition of different EC droplets (mass fraction) used for modeling.

**Figure 10(b)** shows the total deposition of EC-droplets #B2, CSPs and solid particles in the G3- G6 TBU, assuming the same initial particle diameters (i.e., 264 nm ≤ *dd*,*ini* ≤ 3200 nm). It can be observed that with the same initial diameter, the total deposition fraction for the three particles is EC-droplets #B2 < CSPs #1 < solid particles. Clearly, the hygroscopic growth of droplets and CSPs limited their Brownian diffusion, thereby reducing TDE in G3–G6. Since this effect is more prominent for EC-droplets than for CSPs (see **Figure 10**), the latter therefore has higher total deposition efficiency values. In other words, CSPs #1 deposit more in the G3–G6 TBU than #B2 EC-droplets due to lower hygroscopic growth and stronger Brownian diffusion effect. It can thus be conjectured that EC-droplets may deposit more than CSPs #1 up to the first bifurcation, due to more pronounced inertial impaction. In contrast, those EC-droplets tend to deposit more after the first bifurcation in G3–G6 TBUs and deeper lung regions where Brownian diffusion dominates deposition. Results also indicate the important effect of hygroscopic behaviors of droplets on the accuracy of deposited-dose predictions.
