Effects of Elexacaftor/Tezacaftor/Ivacaftor on the Sinonasal Airspace in Cystic Fibrosis.

Abstract

People with Cystic Fibrosis (CF) experience significant sinonasal airway opacification, leading to chronic airway-related conditions. The triple combination therapy Elexacaftor/Tezacaftor/Ivacaftor (ETI) has emerged as a therapeutic option for CF. This study uses volumetric quantification technique to evaluate changes in CF sinonasal airway patency pre-ETI and post-ETI. Anatomically accurate person-specific three-dimensional sinonasal airspaces were reconstructed from radiographical images of 19 people (12 male, 7 female) with CF, pre-ETI and post-ETI. Sinonasal airspace surface area, volume, and surface-area-to-volume ratio were calculated pre-ETI and post-ETI. Pre-ETI and post-ETI sinonasal airspace changes in these computed parameters were corrected with changes in both Lund-Mackay and SNOT-22 scores. Median (IQR) surface area and volume increased significantly from pre-ETI (Surface Area: 251.97 cm² (43.71); Volume: 44.86 cm³ (20.72)) to post-ETI (Surface Area: 295.77 cm² (31.34); Volume: 61.03 cm³ (14.21)), with respective p < 0.01 per computed parameter. Furthermore, median surface-area-to-volume ratio (IQR) was significantly different; pre-ETI: 0.053 cm^-1 (0.007); post-ETI: 0.052 cm^-1 (0.013); p = 0.04. Pre-ETI to post-ETI improvement changes in surface area and volume significantly correlated with corresponding changes in Lund-Mackay scores (Surface Area: R = -0.78, p < 0.01; Volume: R = -0.68, p < 0.01), but correlated weakly with corresponding changes in patient-reported SNOT-22 scores (Surface Area: R = -0.13, p = 0.62; Volume: R = -0.06, p = 0.82). People with CF treated with ETI exhibited a significant increase in sinonasal airway patency, as evidenced by volumetric quantification analysis of surface area and volume differences. These increases in both parameters showed strong significant correlations with Lund-Mackay scores; however, no such correlations were observed with SNOT-22 scores.