Stochastic Modeling of Particle Deposition in Lungs of Cystic Fibrosis Patients

Abstract

A stochastic model describing particle deposition in cystic fibrosis (CF) patients has been developed. The model should help to optimize drug administration in the treatment of CF by exploring those physiologic and physical parameters that are responsible for the delivering of pharmaceutical aerosols to appropriate sites (receptor cells). Concerning the modeling of deposition, changes of the lungs due to CF were expressed by either constant or random scaling of the airway calibers. Additionally, continuous enlargement of the alveoli and the definition of asymmetric breathing cycles (different lengths for inhalation and exhalation time) were carried out. Application of these model considerations to three different age groups (infants, children, and adults) showed that permanent reduction of the airway calibers generally increases deposition in the tracheobronchial tree by more than 100% with respect to healthy controls. The fraction of particles deposited in the alveoli and alveolar ducts may be decreased at the same time. These tendencies are even more pronounced by the simulation of emphysema and by extending exhalation time with respect to inhalation time. Relative particle fractions deposited in the tracheobronchial compartment significantly increase from infant to adult.

Early Airway Structural Changes in Cystic Fibrosis Pigs as a Determinant of Particle Distribution and Deposition

“…3) We were able to perform CFD modeling on airway trees from newborn CF pigs, thereby studying the primary effect of congenital airway narrowing in CF and eliminating secondary effects from infection, inflammation, and mucus obstruction. While our findings are consistent with recent experimental and stochastic aerosol studies (5, 6, 18, 27, 42, 43), several caveats exist. 1) The airway geometry was assumed to be rigid in this study.…”

“…These findings could correlate to greater bacterial deposition on the airway surface. Furthermore, with disease progression airway lumen obstruction occurs in CF secondary to mucus accumulation and this airway narrowing might be expected to cause similar effects and/or worsen the congenital abnormalities (42). It will be interesting in future studies to determine if particle deposition patterns obtained from newborn CF airway geometries predict the sites of airway disease development later in CF.…”