Open Access Original research

Liquid hyper-absorption as a cause of increased DTPA clearance in the cystic fibrosis airway

Timothy E Corcoran12*, Kristina M Thomas3, Stefanie Brown1, Michael M Myerburg1, Landon W Locke1 and Joseph M Pilewski14

Author Affiliations

1 Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, UPMC MUH NW628, 3459 Fifth Ave, Pittsburgh, PA 15213, USA

2 Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA

3 Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, USA

4 Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA

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EJNMMI Research 2013, 3:14  doi:10.1186/2191-219X-3-14

Published: 27 February 2013

Abstract

Background

Airway liquid hyper-absorption is a key pathophysiological link between the genetic mutations of cystic fibrosis (CF) and the development of lung disease. Here we consider whether the clearance of radiolabeled diethylene triamine pentaacetic acid (DTPA) might be used to detect changes in airway liquid absorption.

Methods

Tc99m-DTPA was added to the apical (luminal) surface of primary human bronchial epithelial cell cultures from CF and non-CF lungs. Liquid absorption rates were assessed using an optical method and compared to DTPA absorption rates. Measurements of transepithelial electrical resistance (TER) were made to determine the effect of epithelial permeability. DTPA absorption was assessed after stimuli known to influence liquid absorption (volume addition and osmotic gradients) and in cultures containing different proportions of CF and non-CF cells.

Results

DTPA absorption rate was increased in CF cultures matching previous in vivo studies in individuals with CF. DTPA and liquid absorption rates were proportional. There was no relationship between TER and DTPA absorption rate when measured in individual cultures. Apical volume addition increased both DTPA and liquid absorption rates. DTPA absorption increased in a dose-dependent manner after basolateral mannitol addition was used to create transepithelial osmotic gradients favoring liquid absorption. Conversely, apical mannitol (a candidate therapy) slowed DTPA absorption in CF cultures.

Conclusions

These results imply that DTPA absorption is directly related to liquid absorption, consistent with increased rates of airway surface liquid absorption in the CF airway, and that modification of liquid absorption from osmotic therapies might be detectable through DTPA absorption measurements in vivo.

Trial registration

none

Keywords:
Cystic fibrosis; Airway surface liquid; DTPA; Airway permeability