In patients with fibrotic pulmonary disease such as idiopathic pulmonary fibrosis (IPF), inhaled aerosols deposit mostly in the les affected region of the lung, resulting in suboptimal pharmacokinetics of airway-delivered treatments. Refinement of aerosol delivery technique requires new models to simulate the major alterations of lung physiology associated with IPF, i.e. heterogeneously reduced lung compliance and increased airway caliber.

A novel physical model of the respiratory system was constructed to simulate aerosol drug delivery in spontaneously breathing (negative pressure ventilation) IPF patients. The model comprises upper (Alberta idealized throat) and lower airway (plastic tubing) models and branches into two compartments (Michigan lung model) which differ in compliance and caliber of conducting airway. Aerosol penetration and deposition (using NaF as a model aerosol) in the model was studied in different conditions.

The model was able to reproduce the heterogeneous, compliance-dependent reduction in ventilation and aerosol penetration seen in the fibrotic lung regions in IPF. Addition of intrapulmonary percussive ventilation (IPV) induces a 2-3 fold increase in aerosol penetration in the low-complaince/high airway caliber compartment of the model, demonstrating the responsiveness of the model to therapeutic intervention.

Thanks to the model, we observed that reduced compliance of target lung regions is a critical determinant of aerosol penetration, and thus presumably of aerosol deposition. This finding underscores the need for techniques specifically tailored to enhance delivery of inhaled aerosols to low compliance regions of lungs. Low-frequency IPV (≤3Hz) pulses may represent an attractive option to increase aerosol deposition in fibrotic lung regions.