Functional respiratory imaging assessment of the aerosol deposition of inhaled levofloxacin in cystic fibrosis lungs

Abstract

<b>Background:</b> Functional Respiratory Imaging (FRI) uses CT scans to render&nbsp;3D&nbsp;models of the airway tree to predict aerosol lung deposition&nbsp;through&nbsp;computational fluid dynamics simulations. Quinsair^®&nbsp;is an inhaled formulation of levofloxacin approved in adult cystic fibrosis (CF) patients with chronic&nbsp;Pseudomonas aeruginosa&nbsp;infection. The study aimed to investigate lung deposition when delivered via its approved device Zirela^®. <b>Methods:</b> Aerosol characterization was performed according to the US Pharmacopeia. Mass median aerodynamic diameter&nbsp;was&nbsp;3.56±0.15µm with a geometric standard deviation 1.51±0.04. The aerosol parameters were coupled with the 3D models derived by the CT scans of CF patients with mild (FEV1 &gt;70 percent predicted (pp), n=7) and moderate (FEV1 40-70 pp, n=13) disease; breathing patterns averaged from historical CF patients’ records were used to refine the simulation. <b>Results:</b> Intrathoracic levofloxacin deposition rates were 39.5±13.0% and 37.0±13.6% of the delivered dose (DD) for mild and moderate CF patients, respectively. Deposition was divided into central and peripheral; although the latter was slightly higher in the mild CF group, there were no significant differences between groups (table). Interestingly, a significant correlation was found between the central-to-peripheral deposition (C/P) ratio and the FEV1pp&nbsp;(p=0.039). <b>Conclusion:</b> This FRI study predicts good deposition in patients with mild and moderate CF, and an interesting correlation between FEV1pp and C/P ratio.