BACKGROUND: Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at 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 three monthly for one year post initiation of ivacaftor. Change in ultra-low dose chest CT, blood inflammatory mediators, and sputum microbiome were assessed.
RESULTS: Significant improvements in FEV1, BMI and sweat chloride were observed post-ivacaftor. Improvement in ultra-low dose CT scores were observed after treatment with significant mean reductions in total Bhalla score (p< 0(.)01), peri-bronchial thickening (p = 0(.)035) and extent of mucus plugging (p< 0(.)001). Reductions in circulating inflammatory markers, including IL-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas spp. and an increase in the relative abundance of bacteria associated with more stable community structures. Post-treatment community richness increased significantly (p = 0.03).
CONCLUSIONS: Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It was paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota.
- Journal Article