Method for Measurement of Transepithelial Potential Difference Across the Nasal 
Epithelium: It has been reported that patients with cystic fibrosis have more negative values of 
transepithelial electrical potential difference across the nasal and bronchial epithelium (Knowles 
et.al., 1981). Values are -24.7 ± 0.9 mV in the nose of healthy controls compared to -53.0 ± 
1.8 mV (SEM) in older CF patients (greater than 5 years old). 
Measurement of potential difference is minimally invasive and safe. The reference bridge 
is polyethylene PE240 tubing filled will 3mmol KC1 in 4% agar connected to a sterile needle 
placed subcutaneously on the forearm. The reference bridge is connected through a Calomel cell 
to a volt meter. The exploring bridge is a small polyethylene tube perfused with saline solution 
at 0.2 ml/minute. This is connected to a 3mm of Kcl bridge and then a Calomel cell. The 
electrical potential difference between the exploring and reference electrode is measured by a 
low impedance volt meter. The output of the volt meter is connected to a strip chart recorder. 
The exploring electrode (the fine polyethylene tubing) is used to measure the transepithelial 
potential difference by applying the tip of the electrode to the mucosa under direct vision. The 
measurement of potential difference takes 5-10 minutes, and must be performed prior to the 
application of topical anesthetics. We will also use chloride selective microelectrodes to 
determine the driving force for chloride. 
Chest X-ray: The patients will receive AP and lateral chest x-rays 12 times during the 
performance of this protocol (Table III). 
Method for Perfusion Scans, CT Scans, and Mucociliary Clearance: 
1 . Aerosol Inhalation for Mucociliary Clearance 
Approximately 0.250 mCi of aerosolized Tc-99m-pyrophosphate will be administered 
by nebulization (inhalation through the oropharynx with use of nose plugs). The 
amount of activity will be estimated by the gamma camera count rate. Standard 
dynamic gamma camera images will be obtained for 45 minutes. Quantitative 
measurements of clearance of radioaerosol will be made for both the right and left lung 
large airways. Particle size will be approximately 3 microns. 
2a. High resolution single photon emission tomography (SPECT) of the lungs. 
With patient supine, 2 mCi of Tc-99m-macroaggregated albumin (MAA) will be 
administered by slow intravenous injection. SPECT data will be acquired for 20 
minutes using the Trionix TRIAD high resolution SPECT camera, with reconstruction 
as transverse, coronal and sagittal orthogonal sections. A single fiducial marker will 
be used for later section alignment. 
2b. Thin section CT (1.5 mm slice thickness, 10 cm slice interval) will be acquired using 
a GE 9800 CT scanner. Two slices will be acquired at each of 3 levels. A single 
fiducial marker again will be used. 
2c. SPECT sections will be matched. Each will be graded on a 1-4 scale for abnormality 
(CT qualitatively 1 = normal, 4 = most abnormal). SPECT qualitatively (1 =75- 
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