Examining the ability of empirical correlations to predict subject specific in vivo extrathoracic aerosol deposition during tidal breathing

Abstract

The accuracy of five extrathoracic deposition equations was examined by comparing model predictions with in vivo deposition measurements of 99m Tc-DTPA radiolabeled 0.9% saline delivered via PARI LC Sprint nebulizers in 19 healthy human subjects. The average extrathoracic deposition fraction measured in vivo was 0.19 § 0.10 (average § standard deviation). Comparing to this average value, the extrathoracic deposition fraction predicted by Golshahi et al. equation was the most accurate (0.18 § 0.08), followed by the model described by the ICRP (0.16 § 0.03). However, prediction of subject-specific deposition proved more challenging; the Golshahi et al. model performed the best of the examined equations, yet showed only a small positive correlation between measured and predicted deposition in individual subjects with a Pearson correlation coefficient of 0.34. The difficulties in predicting subject-specific deposition likely result from geometric dissimilarity both within and between subjects, and may require more complicated modeling methods than algebraic equations of the kind examined in this study.

Improved prediction of intersubject variability in extrathoracic aerosol deposition using algebraic correlations

“…Indeed, comparisons of extrathoracic deposition correlation predictions versus in vivo data (Yang et al 2017) support this conclusion, wherein no correlation was able to reliably predict deposition on an individual basis for subjects inhaling nebulized radiolabeled aerosols.…”

“…Total deposition was itself defined as the sum of deposition measured in the subject and the exhaled dose captured on a filter. A summary of the relevant parameters obtained during the in vivo study is presented in Table 1, with additional details available in Yang et al (2017).…”

“…Integrating across a particle size distribution with a defined mass median aerodynamic diameter and geometric standard deviationperformed here by parsing the size distribution into 0.1 mm wide bins between particle sizes of 0.05 and 30.05 mm (and subsequently applying the ICRP 1994 model across each bin using the half-width as the particle diameter)-accounts for the nonlinear relation between deposition and particle size as occurs with polydisperse aerosols. Using the average inhalation flowrates and inhalation volumes as defined in Table 1, an averaged scale factor of 1.04, and the particle size distributions measured in the in vivo study of Yang et al (2017), the ICRP (1994) model predicts an average deposition of 0.170, an upper 95% limit of 0.313, and a lower 95% limit of 0.080.…”

“…As described by Yang et al (2017), participants recruited for the in vivo study at the Royal Prince Alfred Hospital and the University of Sydney in Sydney, Australia were healthy non-smokers 18 to 45 years old with BMIs less than 30 kg/m 3 . Eleven males and eight females of primarily Caucasian or Asian ethnicities were included in the study, with all subjects displaying normal spirometry results.…”

“…The availability of new in vivo deposition data of nebulized aerosols obtained with modern SPECT imaging that includes measurements of each subject's extrathoracic airway dimensions (Yang et al 2017) has allowed us to examine specifically whether deposition models, including that proposed by the ICRP (1994), provide accurate predictions of the intersubject variation in extrathoracic deposition. More importantly, we present an empirically derived methodology for estimating population variance in deposition of nebulized aerosols using the predictive correlation of Golshahi et al (2013).…”