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

ABSTRACT Objectives 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 . Methods 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. Results Median ( IQR ) surface area and volume increased significantly from pre‐ ETI (Surface Area: 251.97 cm 2 (43.71); Volume: 44.86 cm 3 (20.72)) to post‐ ETI (Surface Area: 295.77 cm 2 (31.34); Volume: 61.03 cm 3 (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). Conclusion 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. Level of Evidence 4.