CORK study in cystic fibrosis: sustained improvements in ultra-low-dose chest CT scores after CFTR modulation with ivacaftor
Ronan, Nicola J.; Einarsson, Gisli G.; Twomey, Maria; Mooney, Denver; Mullane, David; NiChroinin, Muireann; O'Callaghan, Grace; Shanahan, Fergus; Murphy, Desmond M.; O'Connor, Owen J.; Shortt, Cathy A.; Tunney, Michael M.; Eustace, Joseph A.; Maher, Michael M.; Elborn, J. Stuart; Plant, Barry J.
Date:
2017-10-14
Copyright:
© 2017, American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.
Full text restriction information:
Access to this item is restricted for 12 months after publication by request of the publisher.
Restriction lift date:
2018-10-14
Citation:
Ronan, N. J., Einarsson, G. G., Twomey, M., Mooney, D., Mullane, D., NiChroinin, M., O’Callaghan, G., Shanahan, F., Murphy, D. M., O’Connor, O. J., Shortt, C. A., Tunney, M. M., Eustace, J. A., Maher, M. M., Elborn, J. S. and Plant, B. J. (2017) ‘CORK study in cystic fibrosis: sustained improvements in ultra-low-dose chest CT scores after CFTR modulation with ivacaftor’, Chest, 153(2), pp. 395-403. doi: 10.1016/j.chest.2017.10.005.
Abstract:
Background: Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of CFTR modulation on multiple modalities of patient assessment. Methods: Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. Results: Significant improvements in FEV1, BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). Conclusions: Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota.
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