David Mullane

Radiologic imaging in cystic fibrosis: cumulative effective dose and changing trends over 2 decades.

OBJECTIVE With the increasing life expectancy for patients with cystic fibrosis (CF), and a known predisposition to certain cancers, cumulative radiation exposure from radiologic imaging is of increasing significance. This study explores the estimated cumulative effective radiation dose over a 17-year period from radiologic procedures and changing trends of imaging modalities over this period. METHODS Estimated cumulative effective dose (CED) from all thoracic and extrathoracic imaging modalities and interventional radiology procedures for both adult and pediatric patients with CF, exclusively attending a nationally designated CF center between 1992-2009 for > 1 year, was determined. The study period was divided into three equal tertiles, and estimated CED attributable to all radiologic procedures was estimated for each tertile. RESULTS Two hundred thirty patients met inclusion criteria (2,240 person-years of follow-up; 5,596 radiologic procedures). CED was > 75 mSv for one patient (0.43%), 36 patients (15.6%) had a CED between 20 and 75 mSv, 56 patients (24.3%) had a CED between 5 and 20 mSv, and in 138 patients (60%) the CED was estimated to be between 0 and 5 mSv over the study period. The mean annual CED per patient increased consecutively from 0.39 mSv/y to 0.47 mSv/y to 1.67 mSv/y over the tertiles one to three of the study period, respectively (P < .001). Thoracic imaging accounted for 46.9% of the total CED and abdominopelvic imaging accounted for 42.9% of the CED, respectively. There was an associated 5.9-fold increase in the use of all CT scanning per patient (P < .001). CONCLUSIONS This study highlights the increasing exposure to ionizing radiation to patients with CF as a result of diagnostic imaging, primarily attributable to CT scanning. Increased awareness of CED and strategies to reduce this exposure are needed.

CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT Scores After CFTR Modulation With Ivacaftor

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 cystic fibrosis transmembrane conductance regulator 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)‐1&bgr;, 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.

37 Clinical outcomes of real world Kalydeco (CORK) study

36 The effect of ivacaftor therapy on clinical and PCR-identified microbial diversity of cystic fibrosis lung infection H. Green1,2, C. Paisey3, A. Smith3, P. Barry1, W. Flight1, A. Jones1,2, J. Marchesi3, A. Horsley1,2, E. Mahenthiralingam3. 1University Hospital of South Manchester NHS Foundation Trust, Manchester Adult Cystic Fibrosis Centre, Manchester, United Kingdom; 2University of Manchester, Institute of Inflammation and Repair, Manchester, United Kingdom; 3Cardiff University, Cardiff School of Biosciences, Cardiff, United Kingdom

CORK Study in Cystic Fibrosis

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 cystic fibrosis transmembrane conductance regulator 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)‐1&bgr;, 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.