Computed tomography correlates with improvement with ivacaftor in cystic fibrosis patients with G551D mutation

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Ivacaftor corrects the cystic fibrosis transmembrane conductance regulator (CFTR) gating defect associated with G551D mutation and is quickly becoming an important treatment in patients with cystic fibrosis (CF) due to this genetic mutation. A single-center study was performed in CF patients receiving ivacaftor to evaluate the usefulness of high resolution computed tomography (HRCT) of the chest as a way to gauge response to ivacaftor therapy. Ten patients with CF were enrolled for at least one year before and after starting ivacaftor. At time of enrollment, mean age was 20.9 ± 10.8 (range 10-44) years. There were significant improvements from baseline to 6 months in mean %FVC (93 ± 16 to 99 ± 16) and %FEV1 (79 ± 26 to 87 ± 28) but reverted to baseline at one year. Mean sweat chloride levels decreased significantly from baseline to one year. Mean weight and BMI improved at 6 months. Weight continued to improve with stabilization of BMI at one year. Chest HRCT showed significant improvement at one year in mean modified Brody scores for bronchiectasis, mucous plugging, airway wall thickness, and total Brody scores. Elevated bronchiectasis and airway wall thickness scores correlated significantly with lower %FEV1, while higher airway wall thickness and mucus plugging scores correlated with more pulmonary exacerbations requiring IV and oral antibiotics respectively. Based on our findings, HRCT imaging is a useful tool in monitoring response to ivacaftor therapy that corrects the gating defect associated with the G551D-CFTR mutation.