DTPA absorption (mean SEM) vs. model fit (line) for four patient subgroups.

<p>(A) Non-CF subjects (n = 9) (B) patients with CF (n = 12). (C) patients with CF after inhalation of hypertonic saline (n = 11). (D) Pediatric patients with CF. Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111972#pone.0111972-Locke1" target="_blank">[10]</a>.</p

Tc-SC retention (mean SEM) vs. model fit (black line) for four patient subgroups.

<p>(A) Non-CF subjects (n = 9) (B) patients with CF (n = 12). (C) patients with CF after inhalation of hypertonic saline (n = 11). (D) Pediatric patients with CF. Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111972#pone.0111972-Locke1" target="_blank">[10]</a>.</p

Left panel: schematic of transport routes in the airway epithelium.

<p>The black and white horizontal arrows represent mucociliary clearance of Tc-SC and DTPA, respectively. DTPA (downward white arrow) absorbs across the airway epithelium via the paracellular route. Water (downward blue arrow) also absorbs across the epithelium via the transcellular and paracellular route. Right panel: normalized Tc-SC (blue circles) and DTPA (green circles) retention curves with the difference between the respective datasets at each time point shown as absorption (red circles) in CF subject 8.</p

Schematic model structure describing the clearance of small molecule and particle probes from the lung.

<p>Initial depositions:  = trachea,  = central,  = peripheral. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111972#pone-0111972-t001" target="_blank">Table 1</a> for full list of model abbreviations.</p

Abbreviations and constants in the work presented herein.

<p>Abbreviations and constants in the work presented herein.</p

Pharmacokinetic Lung Clearance Parameter Values.

<p>Values from this study are shown with 95.</p><p>*PK model in isolated perfused rat lung. Three fluorescent markers used, but only the parameter values for sodium fluorescein (F-Na) are shown since .</p><p>Pharmacokinetic Lung Clearance Parameter Values.</p

AIC Values for Various Model Structures.

<p>The Akaike Information Criterion (AIC) is a metric for determining the most appropriate model for a system, where better fit is balanced against a penalty for overparameterization. Total AIC is shown as calculated from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111972#pone.0111972.e165" target="_blank">Equation 7</a> for all cases: 1) exclude from model structure; 2) include in model structure.</p><p>AIC Values for Various Model Structures.</p

Least-squares solutions for model parameters are shown with 95% confidence intervals for four groups: Non-CF (NCF), CF HS, CF IS, and Pediatric CF (CFP).

<p>(A) MCC rate constant () (). (B) Fraction (FFCA) of large airway with functional MCC. (C) Peripheral lung absorptive rate constant () (). (D) Large airway absorptive rate constant () ().</p

Estimated Tc-SC retention trajectories for three patient subgroups.

<p>Non-CF (red with dashed line), CF IS (green with dotted dashed line), CF HS (blue with line). Shaded envelope characterizes 95% confidence interval (CI) of retention prediction by the model. Pediatric CF subjects not shown due to overlap with adult CF.</p

Estimated DTPA absorption trajectories for three groups.

<p>Non-CF (red with dashed line), CF IS (green with dotted dashed line), CF HS (blue with line). Shaded envelope characterizes 95% confidence interval (CI) of retention prediction by the model. Pediatric CF subjects not shown due to overlap with adult CF.</p