A mathematical model to understand the airway clearance in cystic fibrosis

Abstract

Cystic fibrosis (CF) is characterized by increased ventilation inhomogeneity (VI). The multiple breath washout (MBW) is a lung function test that measures the degree of VI. However, the mechanisms that produce VI in CF are not well understood. Computational models that mimic lung anatomy and physiology are available, but only few of them have dealt in depth with the airway clearance. Our aim was to create a lung model with structural and functional characteristics of the CF lung that simulates the entire MBW test. We developed a multi-scale fractal lung model based on anatomical data including big and small airways. We applied systematically changes in parameters that produce VI (compliance, residual airway volume, flow resistance, airway transmissibility), and assessed their effects on the pattern of the MBW curve and on the MBW results. Variabilities in compliance and residual airway volume have a direct influence on the MBW pattern and outcomes (lung clearance index changes up to 27% and 24%, respectively). To mimic the increased VI in CF lung disease, systematic changes in airway transmissibility, compliance, and residual volume were applied in the model (Fig.1). We describe an easy-to-apply whole lung model that simulates the MBW test. By applying proper changes in physiological parameters, this model can mimic the MBW test in CF lung disease, which can be used for our better understanding of mechanisms that produce VI in CF.