Use of Asthmatic Pulmonary Function Test Data to Predict Lung Deposition

Abstract

Asthma is a complex disease that alters both breathing patterns and airway morphology. Lack of experimental data or model simulations utilizing realistic in vivo breathing conditions severely limit the ability to assess the relative risk of inhaled pathogens for asthmatics. In this study, a one-dimensional Eulerian modeling approach was used to simulate particle deposition in both asthmatic and healthy subjects. The model was based on the hypothesis that the component reactions of bronchial smooth muscle spasms, submucosal connective tissue swelling, and exudation into the airway lumen manifest themselves as altered lung function, which can be quantified by the parameters measured in subject pulmonary function tests. The asthmatic airway morphology was simulated by altering two parameters, functional residual capacity (FRC) and airway resistance (Raw), which are increased in asthmatic subjects. The amounts in excess of the healthy case were uniquely distributed in the airway generations based on knowledge of the changes in the anatomy and physiology of the airway walls during an asthmatic episode. Specifically, increased Raw was distributed preferentially in the bronchioles and excess FRC was distributed in the pulmonary region. Lung volumes, Raw, and breathing conditions of healthy and asthmatic subjects were compiled from 18 clinical studies. Significant differences were found between healthy and asthmatic Raw, FRC, and tidal volume (TV). In vivo flow fields were simulated using population average TV, breathing frequency, and cycle time fractions. Results showed that using asthmatic conditions in the simulation increased particle deposition over the healthy case by an average of 54% for the range of particles tested. This deposition increase was large compared to the difference due to intersubject variability of the healthy case. Comparisons to experimental data were limited by the number of unreported parameters. This study showed that using asthmatic breathing conditions resulted in significantly different particle deposition compared to using the controlled breathing patterns reported in experimental studies. Therefore, caution should be taken when using experimental data to assess particle deposition in vivo if realistic subject breathing is not used.