Theoretical and experimental approaches to the deposition and clearance of ultrafine carcinogens in the human respiratory tract

Abstract

Introduction: Although inhaled ultrafine particles (UFPs) represent serious lung burdens and are thus responsible for a remarkable number of respiratory diseases (including cancer), only limited information on their deposition and clearance in the lung compartments is available. The study presented here tries to overcome this deficit by using a detailed theoretical approach to UFP behavior in the lungs. Methods: The deposition model used in this context is based upon a stochastic lung geometry and the generation of single-particle trajectories in the tracheobronchial tree according to the random walk algorithm. Simulation of UFP clearance is conducted with the help of a multi-compartment model that considers cellular/non-cellular sites of temporary particle storage as separate compartments. Results: As predicted by the models and confirmed by experimental findings, deposition of UFPs by Brownian motion takes place in both the upper and lower compartments of the respiratory tract. Alveolar accumulation of particulate mass increases proportionally with the inhalative flow rate. Clearance of UFPs is chiefly dominated by slow mechanisms with respective half-times ranging from several days to months. Discussion: Modeling of UFP behavior in the respiratory tract represents an appropriate tool for forthcoming medical studies on this particle class, but it needs to be subjected to further refinements. • As outlined by this study, alveolar deposition of UFPs, correlating with a noticeable risk of malignant transformations and cancer development, is determined by a number of factors, including effective particle size and velocity of particle transport in the conducting airways. • With the help of appropriately validated models, respective predictions on the pulmonary burdens of UFP after short-term or long-term exposure can be made. In the case of subjects suffering from bronchial and/or alveolar UFP overloads, respective clearance approaches may be applied to simulate particle removal scenarios. © Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.