The Effects of Simulated Airway Diseases and Affected Flow Distributions on Aerosol Deposition

BACKGROUND: Experimental and theoretical aspects of targeted drug delivery have been addressed several times in this journal. Herein, a computational study of particle deposition patterns within healthy and diseased lungs has been performed, using a validated aerosol dosimetry model and a flow-resistance model. OBJECTIVE: To evaluate to what extent the uneven flow distributions produced by the physical manifestations of respiratory diseases affect the deposition patterns of inhaled aerosolized drugs. METHODS: Diseases were simulated by constrictions and blockages, which caused uneven flow distributions. Respiratory conditions of sedentary and pronounced activities, and of particle sizes ranging from 0.1 mu m to 10 mu m, were used as the basis for the calculated deposition patterns. RESULTS: Findings are presented that describe flow as a function of airway disease state (eg, flow redistribution). Data on the effects of lung morphologies, healthy and diseased, on compartmental (tracheobronchial and pulmonary) and local (airway generation) aerosol deposition are also given. By formulating these related factors, modeling results show that aerosolized drugs can be effectively targeted to appropriate sites within lungs to elicit positive therapeutic effects. CONCLUSIONS: We have addressed the complexities involved when taking into account interactive effects between diseased airway morphologies and redistributed air flows on the transport and deposition of inhaled particles. Our results demonstrate that respiratory diseases may influence the deposition of inhaled drugs used in their treatment in a systematic and predictable manner. We submit this work as a first step in establishing the use of mathematical modeling techniques as a sound scientific basis to relate airway diseases and aerosolized drug delivery protocols.