In silico evaluation of particle transport and deposition in the airways of individual patients with chronic obstructive pulmonary disease

Inhalation therapy can effectively treat chronic obstructive pulmonary disease (COPD), but the physical factors determining the appropriate aerosol delivery into the targeted airways remain unclear. The problem is nontrivial because pulmonary structures differ among individual patients with COPD and depend on the severity of the disease. In an in silico evaluation, the present study investigates the differences in particle transport and deposition in the airways of three patients with different degrees of COPD. Specific pulmonary airway models were reconstructed based on the computed tomography data of three patients with a different degree of COPD severity. The transport and deposition of inhaled particles in the airways were evaluated in a computational fluid dynamics simulation and a Lagrangian multiphase model. The sizes of the inhaled particles (1.0, 2.5, 5.5, 8.5, and 10.0 mu m) were representative of drug particles delivered from inhalation devices, including dry powder inhalers (DPIs). The deposition behaviors of the inhaled particles strongly depended on the individual geometrical structure of the airways. The largest inhaled particles (10.0 mu m) were most strongly affected by inertia and were deposited mostly in the oropharynx; consequently, they were rare in the bronchi. In contrast, the smallest inhaled particles (1.0 mu m) were effectively delivered distally with the airflow. The spatial distributions and amounts of deposited particles in the airways obviously differed among the three COPD patients. Small particles are preferred as they can penetrate the inner lung regions. The results can assist the design and development of powder formulations and DPIs for patients with various severities of COPD.

Automated summary

Inhalation therapy is an effective treatment for COPD, but the factors affecting aerosol delivery into targeted airways are not well understood. This study used computational simulations to investigate particle transport and deposition in the airways of three COPD patients with different degrees of severity. The results showed that the deposition behavior of inhaled particles strongly depended on individual airway structure. Smaller particles were more effectively delivered distally with the airflow, while larger particles were mainly deposited in the oropharynx. The spatial distribution and amount of deposited particles varied among the three patients. The findings can guide the design and development of powder formulations and DPIs for COPD patients with different severities.