Ultra-Low Dose Thoracic CT Derived Morphomics in Cystic Fibrosis Patients on Elexacaftor/Tezacaftor/Ivacaftor.

Abstract

Rationale: In cystic fibrosis (CF), body composition alterations are observed. Prevalence of obesity in CF is increasing with evidence suggesting a subsequent increase in cardiometabolic risk. We sought to assess body composition using analytic morphomics (AM) from ultra-low dose thoracic CT scans in CF patients on the triple CFTR modulator therapy, Elexacaftor/Tezacaftor/Ivacaftor (ETI). Objective Our objective was to use analytical morphomics on routine ultra-low dose CTs to assess patterns of change in body composition in CF patients on ETI therapy. Methods Forty-two CF patients on ETI who had baseline and follow up ultra-low dose thoracic CT imaging were retrospectively analysed. The CTs were acquired at a radiation dose equivalent to 2 frontal chest x-rays using our previously published acquisition parameters. The Bhalla score was used as a marker of structural lung disease severity. AM variables including: cross sectional area (CSA) and attenuation of pectoralis muscle, visceral fat (epicardial and upper abdominal) and subcutaneous fat were extracted using the validated image segmentation software, CoreSlicer. Paired samples mean testing (Wilcoxon matched pairs signed rank test) and Spearman rank correlation analyses were performed. Results Total Bhalla scores significantly improved over time in patients on ETI (p < 0.0001). In addition, body composition also changed with an increase in the CSA of subcutaneous, and epicardial visceral fat (p values < 0.0001, and 0.0062, respectively). In those with a normal BMI at follow up, epicardial, and subcutaneous fat had also increased significantly in the interval (p = 0.0066, and 0.0002, respectively). Conclusion In CF, ETI produced a significant improvement in structural lung disease over time, however also resulted in an increase in visceral and subcutaneous fat. The AM methodology presented herein, may help identify those patients for aggressive primary prevention strategies and permit the creation of more personalised nutritional plans.