Absorptive clearance of DTPA as an aerosol-based biomarker in the cystic fibrosis airway

Abstract

Biomarkers providing in vivo quantification of the basic elements of cystic fibrosis (CF) lung disease are needed. A study was performed to determine whether the absorption of a small radiolabelled hydrophilic molecule (Indium-111 (In-)DTPA) would be increased in CF airways. DTPA clearance has been used previously to assess epithelial permeability and may also be useful for quantifying liquid absorption. The absorptive clearance rate of DTPA was quantified in 10 CF and 11 control subjects using a novel aerosol technique. Subjects inhaled an aerosol containing nonabsorbable technetium-99m sulfur colloid (Tc-SC) particles and In-DTPA. Tc-SC clearance from the lung is exclusively mucociliary, while In-DTPA is cleared by both absorption and mucociliary clearance. The difference between the In-DTPA and Tc-SC clearance rates estimates In-DTPA absorption. Tc-SC (mucociliary) clearance was similar in central and peripheral zones in CF and non-CF lungs. Total In-DTPA clearance was increased in both zones in CF lungs. The absorptive component of In-DTPA clearance was increased in the airway-dominated central lung zones in CF (42% x h( -1) versus 32% x h(-1), p = 0.03). The absorption of In-DTPA is increased in the CF airway. Further study is needed to understand the relative roles of fluid absorption, inflammation and other mechanisms potentially affecting epithelial permeability and DTPA absorption.

Trial registration: ClinicalTrials.gov NCT00248755 NCT00541190.

Figures

FIGURE 1

Central and peripheral lung clearance rates of Technetium 99m sulfur colloid (Tc-SC) in CF and control subjects. This represents the rate of mucociliary clearance. Data is reported as percent cleared over 60 minutes. Central lung p=0.51, peripheral lung p=0.62 by Mann-Whitney test.

FIGURE 2

Central and peripheral lung clearance rates of Indium 111 DTPA (In-DTPA) in CF and control subjects. In-DTPA is cleared through both adsorptive and mucociliary routes. Data is reported as percent cleared over 60 minutes. Central lung p=0.05, peripheral lung p=0.04 by Mann-Whitney test.

FIGURE 3

The absorptive component of In-DTPA clearance in central and peripheral lung zones in CF and control subjects. Absorptive clearance is calculated as the difference between the total In-DTPA clearance rate and the Tc-SC (mucociliary) clearance rate in each subject. Data is reported as percent cleared over 60 minutes. Central lung p=0.03, peripheral lung p=0.14 by Mann-Whitney test.