COMPUTATIONAL FLUID DYNAMICS (CFD) SIMULATIONS OF AEROSOL DEPOSITION IN THE LUNGS

In the current study, Large Eddy Simulations (LES) are used to investigate the transport and deposition of inhaled aerosol particles (dp = 0.1, 0.5, 1, 2.5, 5, 10 μm) in a realistic geometry of the human airways under steady inhalation. The effects of electrostatic charge and lower generation airway narrowing caused by Chronic Obstructive Pulmonary Disease (COPD) on particle transport and deposition are examined for various flowrates (sedentary 15.2 lt/min, light 30 lt/min and heavy activity 60 lt/min). Results show that the mean flow structures at the three flowrates are qualitatively similar regardless of Reynolds number. Similar swirling motions are generated from the impingement of the laryngeal jet on the tracheal front wall. However, higher turbulent intensities that persist further downstream in the trachea and the main bronchi are observed as the flowrate is increased. The Deposition Efficiency (DE) of particles is increased with the flowrate due to greater inertial impaction. The majority of the larger particles are filtered in the mouththroat region, while 0.1, 0.5 and 1μm diameter particles have similar DE at a given flowrate. The effect of charge on DE of particles is more pronounced for smaller particles; 1000 elementary charge units on 0.1, 0.5, 1 and 2.5 μm diameter particles results in approximately 7, 3, 2.5 and 1.5 times greater overall DE than that with no charge, respectively. Obstructed lower generation airways result in enhanced deposition due to impaction caused by higher velocities in these airways. INTRODUCTION Computational Fluid Dynamics (CFD) techniques are being increasingly used to simulate flow behavior in the human respiratory system. Recent works include Reynolds Averaged Navier-Stokes (RANS) simulations (Luo & Liu, 2008), Large Eddy Simulations (LES) (Choi et al. (2009), Radhakrishnan & Kassinos (2009)) and Direct Numerical Simulations (DNS) (Lin et al., 2007). Both idealized model geometries and geometries obtained from medical imaging have been used. The deposition of therapeutic or pollutant xenobiotic particles is dependent on the characteristics of the respiratory flow by which they are transported (Xi & Longest, 2007). The ultimate goal of the application of CFD techniques is an in-depth understanding of the fate of inhaled pollutants, including deposition and possible mucus clearance, as well as the efficient pulmonary delivery of drugs targeting respiratory or systemic diseases. An important parameter affecting both the characteristics of the airflow and particle transport is the inhalation rate. A higher flowrate causes an earlier transition to turbulence and higher overall turbulence levels. Johnstone et al. (2004) studied experimentally the velocity fields in an idealized model of the human extrathoracic airway during steady inspiration and found that Reynolds stress profiles were highly dependent on inhalation flowrate, especially in the separated shear layer regions. Flow rates of 15, 30 and 60 lt/min are considered to correspond to sedentary, light and heavy activity conditions, respectively (Xi & Longest, 2007). In drug delivery applications, medical devices such as nebulisers, Metered Dose Inhalers (MDI) and Dry Powder Inhalers (DPI) often generate electrostatically charged aerosols (Kwok (2005), Kwok & Chan (2009)). In addition, pollution aerosols generated in the environment or in occupational settings, may have charges well above the Boltzmann equilibrium level. Thus, consideration of electrostatic particle properties must be taken into account in human health risk assessments (Forsyth, 1998). Theoretical studies in lung models (Yu, 1985), experiments in man (Prodi, 1985) and clinical measurements confirmed that charge carried by particles enhances the deposition of the particles in the lung considerably. This is not desirable for drugs intended for systemic uptake, which must pass into the blood through the alveolar epithelium and thus early deposition is unwanted, but might be desirable for drug delivery in certain upper regions of the airway tree or even leveraged for the removal of pollutant particles using electrostatic charge effects (Ali, 2008). Chronic Obstructive Pulmonary Disease (COPD) is a common and life-threatening condition, causing high morbidity and mortality in industrialized countries (Hea, 2008). COPD is characterized by airflow obstruction that is not fully reversible, caused by airway narrowing resulting from the combination of increased mucus, excess tissue, and in1 June 30 July 3, 2015 Melbourne, Australia 9 6D-1