Quantifying inter-subject variability in Pulmonary Drug Delivery using Monte Carlo simulations*

The trajectories of inhaled particles in the distal lung depend on the unique geometry of each person's respiratory tract. Therefore, variation in lung anatomy is a major reason why different people respond to inhaled medications differently. To quantify the extents of inter-subject variability in large and diverse populations, we perform Monte-Carlo simulations (for 6000 realizations) of a stochastic asymmetric multi-path model of the human airways. We introduce stochasticity in the branching asymmetry to generate biologically realistic and representative models of the lung geometry. We report the statistical variations of regional particle deposition as a function of several key parameters - branching asymmetry, particle size, breathing period, bronchoconstriction, etc. We show how particles of specific sizes preferentially deposit in the deep lung and others in the upper airways, how asymmetry can decrease deposition in the upper airways and how bronchoconstriction can alter the distribution of particle deposition across the lung. These insights will be valuable for determining drug dosages as well as design and choice of delivery devices (inhalers/nebulizers).