Absorptive Clearance in the Cystic Fibrosis Airway

University of Pittsburgh21 enrolled

Overview

The objective of this overall project is to develop a new aerosol-based technique for quantifying liquid absorption in the airways of subjects with cystic fibrosis(CF) that can be used to help develop new therapies. In CF, mutations in the CF gene result in dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ion channel on the cells that line the airway epithelium, causing improper fluxes of ions such as sodium, chloride, and bicarbonate. The so called "low volume" hypothesis of CF pathogenesis contends that abnormal absorption of ions from the airways causes excessive absorption of liquid, resulting in an airway surface liquid layer that is dehydrated and difficult to clear. Here we are measuring the absorption rate of a radiolabeled small molecule (DTPA) from the lungs of cystic fibrosis patients and healthy controls. We hypothesize that the molecule will absorb more quickly in cystic fibrosis patients. Further studies will be performed to determine if DTPA absorption is related to liquid absorption in the airways.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Cystic Fibrosis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Cystic fibrosis subjects and healthy controls * Age ≥ 18 years * Diagnosis of cystic fibrosis as determined by sweat test or genotype and clinical symptoms (CF subjects) * Clinically stable as determined by the investigator (pulmonologist) Exclusion Criteria: * Reactive airways disease * Tobacco smokers (regular smoking within 6 months of enrollment) * Positive urine pregnancy test on the day of testing * FEV1p value of \< 50% * SaO2 \< 92%, or if they require supplemental oxygen. * Subjects performing other radioisotope studies within the last 2 weeks will be excluded. * Healthy subjects with any history of lung disease will be excluded. * Women currently breastfeeding * Subjects not willing to stop treatments with inhaled hypertonic saline for 48 hours in advance of the study.

Outcomes

Primary Outcomes

Absorptive Clearance Rate

The absorptive clearance rate is the percentage of the radiolabeled small molecule DTPA that is cleared through absorption over a 60 minute period. Total DTPA clearance includes absorptive and mucociliary components. The mucociliary component is determined by measuring the clearance of a radiolabeled particle over the same period (Technetium 99m sulfur colloid; Tc-SC), and subtracted from total DTPA clearance in order to determine the absorptive component. Here we specifically report absorption from the central lung zone to capture the behavior within the airways.

Time frame: single measurement

Secondary Outcomes

Mucociliary Clearance Rate

Mucociliary clearance rate represents the rate at which the lungs clear an inhaled particulate. Here it specifically represents the percentage of inhaled Technetium 99m sulfur colloid cleared from the lungs over a 60 minute period. This is reported based on "whole lung" areas to allow comparisons with previous studies.