Ultra-Low Dose Thoracic Computed Tomography-derived Morphomics in Patients with Cystic Fibrosis on Elexacaftor/Tezacaftor/Ivacaftor

Rationale: In cystic fibrosis (CF), body composition alterations are observed. The 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 from ultra-low-dose thoracic computed tomography (CT) scans in patients with CF on the triple CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI). Objectives: Our objective was to use analytical morphomics on routine ultra-low-dose CTs to assess patterns of change in body composition in patients with CF on ETI therapy. Methods: Forty-two patients with CF on ETI who had baseline and follow-up ultra-low-dose thoracic CT imaging were retrospectively analyzed. The CTs were acquired at a radiation dose equivalent to two frontal chest X-rays using our previously published acquisition parameters. The Bhalla score was used as a marker of structural lung disease severity. Analytic morphomics variables, including cross-sectional area 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 cross-sectional area of subcutaneous and epicardial visceral fat (P < 0.0001 and P = 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 P = 0.0002, respectively). Conclusions: In CF, ETI produced a significant improvement in structural lung disease over time; however, it also resulted in an increase in visceral and subcutaneous fat. The analytic morphomics methodology presented herein may help identify those patients for aggressive primary prevention strategies and permit the creation of more personalized nutritional plans.