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 microm to 10 microm, 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.
Apiou-Sbirlea
Gabriela
G
Biomedical Research Institute Mondor (Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR 955), Department of Cell and Respiratory Biomechanics, School of Medicine, 3rd floor, Office 3060, 8 Rue du Général Sarrail, Créteil 94010, France. gabriela.apiou@inserm.fr
Katz
Ira M
IM
Martonen
Ted B
TB
D000336:Aerosols / Q000627:therapeutic use*; D003198:Computer Simulation; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000503:physiopathology; D008954:Models, Biological; D012123:Pulmonary Ventilation / Q000502:physiology; D012212:Rheology
D000336:Aerosols