Understanding the fate of inhaled aerosol particles in healthy and diseased lungs may help in assessing the toxic health effects of airborne particulate matter or the efficiency of therapeutic drugs delivered through the lung. This dissertation focused on determining aerosol particle deposition patterns in healthy and emphysematous rats lungs by utilizing experimental and numerical methods. In the experimental part of the study, both airway morphometry and deposition patterns were determined by MRI. In the morphometry study, healthy rat lungs were imaged in vivo. Airway geometries were extracted from the MR images and the morphometric dimensions were validated against previous studies. In the aerosol deposition study, healthy and emphysematous rats were exposed by mechanical ventilation to iron-oxide particles with 1.22[mu]m mass mean aerodynamic diameter (MMAD). The lungs were imaged with a MR gradient echo sequence and the signal decay rate, R*₂, was calculated from the signal intensity images. Data showed a significantly higher R*₂ in the rats exposed to particles than in the control rats (no aerosol exposure) both for the healthy and emphysematous groups. A calibration experiment showed that concentration of deposited particles in tissue samples was linearly related to R*₂. Particle concentration and relative dispersion of particle deposition sites in all lung lobes tended to be higher in the emphysematous rats compared to the healthy rats. To further study particle deposition sites in the rat lungs, multi-scale computational fluid dynamics (CFD) simulations were performed. The global resistance and compliance of the rat lungs were determined by solving a global resistance/compliance (RC) model. This same RC model was then employed as Neumann boundary conditions in the 0D-3D simulations. Deposition and distribution of particles to the rat lobes was determined for particles with the same diameter as those used in the experiments. Simulations were performed representing healthy, homogeneous and localized emphysema. Emphysema location was determined by utilizing findings from the experimental data. Deposition in the 3D model was higher in the emphysematous cases compared to the healthy cases. Additionally, there was an increase in delivery of particle-laden air to the diseased regions of the lung, compared to the healthy regions. Good agreement was found when comparing the simulated normalized delivery of particles to each lobe to the normalized experimental deposition data. This work is the first to compare deposition sites found numerically and experimentally in both healthy and emphysematous lungs. In future studies, the multi-scale CFD models developed here may be advanced to include particle tracking downstream of the 3D model

Emission measurements are available in the literature for a wide variety of field burns and laboratory experiments, although previous studies do not always isolate the effect of individual features such as fuel moisture content (FMC). This study explores the effect of FMC on gaseous and particulate emissions from flaming and smouldering combustion of four different wildland fuels found across the United States. A custom linear tube-heater apparatus was built to steadily produce emissions in different combustion modes over a wide range of FMC. Results showed that when compared with flaming combustion, smouldering combustion showed increased emissions of CO, particulate matter and unburned hydrocarbons, corroborating trends in the literature. CO and particulate matter emissions in the flaming mode were also significantly correlated with FMC, which had little influence on emissions for smouldering mode combustion, when taking into account the dry mass of fuel burned. These variations occurred for some vegetative fuel species but not others, indicating that the type of fuel plays an important role. This may be due to the chemical makeup of moist and recently live fuels, which is discussed and compared with previous measurements in the literature.

Aerosolized drugs are increasingly being used to treat chronic lung diseases or to deliver therapeutics systemically through the lung. The influence of disease, such as emphysema, on particle deposition is not fully understood. With the use of magnetic resonance imaging (MRI), the deposition pattern of iron oxide particles with a mass median aerodynamic diameter of 1.2 μm was assessed in the lungs of healthy and elastase-treated rats. Tracheostomized rats were ventilated with particles, at a tidal volume of 2.2 ml, and a breathing frequency of 80 breaths/min. Maximum airway pressure was significantly lower in the elastase-treated (Paw = 7.71 ± 1.68 cmH2O) than in the healthy rats (Paw = 10.43 ± 1.02 cmH2O; P < 0.01). This is consistent with an increase in compliance characteristic of an emphysema-like lung structure. Following exposure, lungs were perfusion fixed and imaged in a 3T MR scanner. Particle concentration in the different lobes was determined based on a relationship with the MR signal decay rate, R2 (*). Whole lung particle deposition was significantly higher in the elastase-treated rats (CE,part = 3.03 ± 0.61 μm/ml) compared with the healthy rats (CH,part = 1.84 ± 0.35 μm/ml; P < 0.01). However, when particle deposition in each lobe was normalized by total deposition in the lung, there was no difference between the experimental groups. However, the relative dispersion [RD = standard deviation/mean] of R2 (*) was significantly higher in the elastase-treated rats (RDE = 0.32 ± 0.02) compared with the healthy rats (RDH = 0.25 ± 0.02; P < 0.01). These data show that particle deposition is higher and more heterogeneously distributed in emphysematous lungs compared with healthy lungs.

While mounting evidence suggests that wildland fire smoke (WFS) inhalation may increase the burden of cardiopulmonary disease, the occupational risk of repeated exposure during wildland firefighting remains unknown. To address this concern, we evaluated the cardiopulmonary function in mice following a cumulative exposure to lab-scale WFS equivalent to a mid-length wildland firefighter (WLFF) career. Dosimetry analysis indicated that 80 exposure hours at a particulate concentration of 22 mg/m3 yield in mice the same cumulative deposited mass per unit of lung surface area as 3600 h of wildland firefighting. To satisfy this condition, male Apoe-/- mice were whole-body exposed to either air or smoldering Douglas fir smoke (DFS) for 2 h/day, 5 days/week, over 8 consecutive weeks. Particulate size in DFS fell within the respirable range for both mice and humans, with a count median diameter of 110 ± 20 nm. Expiratory breath hold in mice exposed to DFS significantly reduced their minute volume (DFS: 27 ± 4; Air: 122 ± 8 mL/min). By the end of the exposure time frame, mice in the DFS group exhibited a thicker (DFS: 109 ± 3; Air: 98 ± 3 μm) and less distensible (DFS: 23 ± 1; Air: 28 ± 1 MPa-1) aorta with reduced diastolic blood augmentation capacity (DFS: 53 ± 2; Air: 63 ± 2 kPa). Cardiac magnetic resonance imaging further revealed larger end-systolic volume (DFS: 14.6 ± 1.1; Air: 9.9 ± 0.9 μL) and reduced ejection-fraction (DFS: 64.7 ± 1.0; Air: 75.3 ± 0.9 %) in mice exposed to DFS. Consistent with increased airway epithelium thickness (DFS: 10.4 ± 0.8; Air: 7.6 ± 0.3 μm), airway Newtonian resistance was larger following DFS exposure (DFS: 0.23 ± 0.03; Air: 0.20 ± 0.03 cmH2O-s/mL). Furthermore, parenchyma mean linear intercept (DFS: 36.3 ± 0.8; Air: 33.3 ± 0.8 μm) and tissue thickness (DFS: 10.1 ± 0.5; Air: 7.4 ± 0.7 μm) were larger in DFS mice. Collectively, mice exposed to DFS manifested early signs of cardiopulmonary dysfunction aligned with self-reported events in mid-career WLFFs.

Image-based in silico modeling tools provide detailed velocity and particle deposition data. However, care must be taken when prescribing boundary conditions to model lung physiology in health or disease, such as in emphysema. In this study, the respiratory resistance and compliance were obtained by solving an inverse problem; a 0D global model based on healthy and emphysematous rat experimental data. Multi-scale CFD simulations were performed by solving the 3D Navier-Stokes equations in an MRI-derived rat geometry coupled to a 0D model. Particles with 0.95 μm diameter were tracked and their distribution in the lung was assessed. Seven 3D-0D simulations were performed: healthy, homogeneous, and five heterogeneous emphysema cases. Compliance (C) was significantly higher (p = 0.04) in the emphysematous rats (C = 0.37 ± 0.14 cm(3)/cmH2O) compared to the healthy rats (C = 0.25 ± 0.04 cm(3)/cmH2O), while the resistance remained unchanged (p = 0.83). There were increases in airflow, particle deposition in the 3D model, and particle delivery to the diseased regions for the heterogeneous cases compared to the homogeneous cases. The results highlight the importance of multi-scale numerical simulations to study airflow and particle distribution in healthy and diseased lungs. The effect of particle size and gravity were studied. Once available, these in silico predictions may be compared to experimental deposition data.

While it is well recognized that pulmonary deposition of inhaled particles is lowered in microgravity (μG) compared with gravity on the ground (1G), the absence of sedimentation causes fine particles to penetrate deeper in the lung in μG. Using quantitative magnetic resonance imaging (MRI), we determined the effect of gravity on peripheral deposition (DEPperipheral) of fine particles. Aerosolized 0.95-μm-diameter ferric oxide particles were delivered to spontaneously breathing rats placed in plethysmographic chambers both in μG aboard the NASA Microgravity Research Aircraft and at 1G. Following exposure, lungs were perfusion fixed, fluid filled, and imaged in a 3T MR scanner. The MR signal decay rate, R2*, was measured in each voxel of the left lung from which particle deposition (DEP) was determined based on a calibration curve. Regional deposition was assessed by comparing DEP between the outer (DEPperipheral) and inner (DEPcentral) areas on each slice, and expressed as the central-to-peripheral ratio. Total lung deposition tended to be lower in μG compared with 1G (1.01 ± 0.52 vs. 1.43 ± 0.52 μg/ml, P = 0.1). In μG, DEPperipheral was larger than DEPcentral (P < 0.03), while, in 1G, DEPperipheral was not significantly different from DEPcentral. Finally, central-to-peripheral ratio was significantly less in μG than in 1G (P ≤ 0.05). These data show a larger fraction of fine particles depositing peripherally in μG than in 1G, likely beyond the large- and medium-sized airways. Although not measured, the difference in the spatial distribution of deposited particles between μG and 1G could also affect particle retention rates, with an increase in retention for particles deposited more peripherally.