What Causes Uneven Aerosol Deposition in the Bronchoconstricted Lung? A Quantitative Imaging Study

Abstract

Background: A previous PET-CT imaging study of 14 bronchoconstricted asthmatic subjects showed that peripheral aerosol deposition was highly variable among subjects and lobes. The aim of this work was to identify and quantify factors responsible for this variability. Methods: A theoretical framework was formulated to integrate four factors affecting aerosol deposition: differences in ventilation, in how air vs. aerosol distribute at each bifurcation, in the fraction of aerosol escaping feeding airways, and in the fraction of aerosol reaching the periphery that is exhaled. These factors were quantified in 12 of the subjects using PET-CT measurements of relative specific deposition sD*, relative specific ventilation sV* (measured with dynamic PET or estimated as change in expansion between two static HRCTs), average lobar expansion F VOL , and breathing frequency measured during aerosol inhalation f N . Results: The fraction of the variance of sD* explained by sV* (0.38), by bifurcation effects (0.38), and by differences in deposition along feeding airways (0.31) were similar in magnitude. We could not directly estimate the contribution of aerosol that was exhaled. Differences in expansion did not explain any fraction of the variability in sD* among lobes. The dependence of sD* on sV* was high in subjects breathing with low f N , but weakened among those breathing faster. Finally, sD*/sV* showed positive dependence on F VOL among low f N subjects, while the dependence was negative among high f N subjects. Conclusion: The theoretical framework allowed us to analyze experimentally measured aerosol deposition imaging data. When considering bronchoconstricted asthmatic subjects, a dynamic measurement of ventilation is required to evaluate its effect on aerosol transport. The mechanisms behind the identified effects of f N and F VOL on aerosol deposition need further study and may have important implications for aerosol therapy in subjects with heterogeneous ventilation.

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

“…Based on what is known about the physics of aerosol deposition, it is likely that most of the variability in peripheral aerosol deposition among lobes, sub-lobes, or any set of peripheral lung regions, can be attributed to one of four distinct factors: 1) differences in regional ventilation; (1,137,138) 2) differences in how the aerosol and air distribute between branches in the series of bifurcations along the pathway feeding the region; (138) 3) variability in the amount of the aerosol that escapes the series of airways along that pathway; (139)(140)(141) and 4) variability in the amount of aerosol that reaches the periphery and is not exhaled. (142) Using the concept of aerosol concentration as the average mass in suspension crossing any point of the bronchial tree, a theoretical framework can be defined to quantify each of the factors that lead to heterogeneous aerosol deposition among lobes: (143) differences in lobar ventilation per unit volume (specific ventilation), uneven splitting of aerosol and air at bifurcations (bifurcation factor), differences in the fraction of aerosol deposited along the feeding airways (escape factor), and differences in the fraction of aerosol that reaches the periphery but escapes via exhalation (retention factor).…”

“…(143) That analysis gave the following results: 1) Differences in lobar specific ventilation (measured from the turnover rate of 13 N washout) and in net branching factors each accounted for more than a third of the variability in deposition among lobes and subjects. The remaining variability was due to differences in deposition along the feeding airways as characterized by their net escape fractions; 2) By exploring inter subject variations in aerosol deposition, it was found that subjects who were breathing slowly (<9 BPM) during nebulization had a strong relationship between regional lobar deposition and their respective regional ventilation, measured with PET.…”

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

“…Regional ventilation as a function of obstructive lung disease can be predicted using whole-lung 1D or lumped parameter models, as describe by Wongviriyawong et al (102) Greenblatt et al (103) recently used theoretical lung modeling to explain changes in lobar deposition of inhaled aerosols associated with bronchoconstriction. Using a different approach, Oakes et al (57) implemented downstream resistance and compliance approximations to predict disease-associated heterogeneous lung ventilation in simulations of aerosol deposition in rat lungs.…”

Regional Ventilation and Aerosol Deposition with Helium-Oxygen in Bronchoconstricted Asthmatic Lungs

“…Given the complexity and multifactorial nature of aerosol deposition, (8) it is impractical and of limited clinical value to study the effect of breathing He-O 2 in humans through highly controlled breathing conditions rarely seen in clinical situations. Instead, we believe that validated and physiologically informed computational models could be a more effective approach to explore how and for whom aerosol delivery with He-O 2 may be of benefit.…”

“…To fulfill this need, in this work we set out to collect such experimental imaging data sets using PET-CT in bronchoconstricted asthmatic subjects receiving aerosol with He-O 2 as a carrier gas under spontaneous uncoached breathing conditions. Together with data previously collected with air as the carrier gas, (8) these data sets will be useful to validate in the future advanced aerosol deposition CFD models under personalized realistic physiological conditions.…”