We are conducting a large, longitudinal study to assess outcome measures and identify optimal patients for a multidose trial of CF gene therapy. Two imaging modalities are being employed: radioisotope deposition scans and high resolution CT. Subjects have undergone these scans on a single occasion, whilst clinically stable. The purpose was: Deposition scan—to determine which patients would be most optimal for topical drug delivery and CT—to assess the suitability of various parameters as efficacy measures. Following inhalation of 99mTc-labelled human serum albumin, planar gamma camera images and SPECT were used to assess 3-D deposition. Images were scored both digitally and visually (I- no defects; II- patchy deposition; III- patchy deposition with large defects; IV- grossly abnormal). HRCT scans were scored by two radiologists on a lobar basis for the following: bronchiectasis (extent/severity), airway wall thickening, mucus plugging and gas trapping. 147 deposition scan were available; digital indices (DI) ranged from 34 (best) to 150 (severely abnormal). Visual scores correlated well with DI (R2 0.63; p<0.001) and both were significantly negatively correlated with FEV1% (p<0.01). Nine Grade IV subjects had a mean (SD) FEV1 of 43.9(4.3)%, significantly lower than groups I-III (p<0.01). On the basis of very poor deposition, this group is considered unsuitable to progress to the trial. Others have deposition scans which suggest that the gene therapy product could be delivered at least moderately well; they will be filtered through other inclusion/exclusion criteria. Potentially reversible components of the HRCT scores are being considered as efficacy outcome measures. As an example, power calculations suggest that our anticipated group size (n=100) would have 80% power to detect a change in wall thickness half that seen with intravenous antibiotics in a previous study. In conclusion, lung imaging techniques have both aided us in the identification of patients to take through into our multi-dose trial and are currently under consideration as efficacy outcomes.
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