title: Quantitative imaging of airway liquid absorption in cystic fibrosis.
abstract: New measures are needed to rapidly assess emerging treatments for cystic fibrosis (CF) lung disease. Using an imaging approach, we evaluated the absorptive clearance of the radiolabeled small molecule probe diethylene triamine penta-acetic acid (DTPA) as an in vivo indicator of changes in airway liquid absorption. DTPA absorption and mucociliary clearance rates were measured in 21 patients with CF (12 adults and nine children) and nine adult controls using nuclear imaging. The effect of hypertonic saline on DTPA absorption was also studied. In addition, in vitro studies were conducted to identify the determinants of transepithelial DTPA absorption. CF patients had significantly increased rates of DTPA absorption compared with control subjects but had similar mucociliary clearance rates. Treatment with hypertonic saline resulted in a decrease in DTPA absorption and an increase in mucociliary clearance in 11 out of 11 adult CF patients compared with treatment with isotonic saline. In vitro studies revealed that ∼ 50% of DTPA absorption can be attributed to transepithelial fluid transport. Apically applied mucus impedes liquid and DTPA absorption. However, mucus effects become negligible in the presence of an osmotic stimulus. Functional imaging of DTPA absorption provides a quantifiable marker of immediate response to treatments that promote airway surface liquid hydration.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Landon W
authors.initials: LW
authors.lastname: Locke
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Myerburg
authors.affiliation: Dept of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Markovetz
authors.affiliation: Dept of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Parker
authors.affiliation: Dept of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Weber
authors.affiliation: Dept of Radiology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Czachowski
authors.affiliation: Dept of Radiology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Harding
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Stefanie L
authors.initials: SL
authors.lastname: Brown
authors.affiliation: Dept of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Nero
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA Dept of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Pilewski
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA corcorante@upmc.edu.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Corcoran
mesh_terms: D000328:Adult; D000336:Aerosols; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009995:Osmosis; D004369:Pentetic Acid / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013147:Spirometry; D013671:Technetium Tc 99m Sulfur Colloid / Q000737:chemistry; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000336:Aerosols; D019275:Radiopharmaceuticals; D013671:Technetium Tc 99m Sulfur Colloid; D004369:Pentetic Acid
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