Background: Cystic Fibrosis (CF) has progressive upper and lower airway involvement.  Impact of CFTR modifier therapies on CF-related upper airway disease, specifically chronic rhinosinusitis, is not characterized. 

Objective: To determine the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on clinical parameters and on chronic rhinosinusitis as measured by changes in sinus computed tomography (CT) metrics in pwCF.

Methods:%predicted FEV1 (ppFEV1), body mass index (BMI) and microbiologic data were collected at initiation of ETI and at 3-month intervals for one year.  Sinus CT was obtained prior to initiation of ETI therapy, and at one year following therapy.  Images were independently analyzed by pulmonology, radiology, and otolaryngology physicians, using the LM (Lund-Mackay) and SL (Sheikh-Lind) scoring systems. 

Results: Sixty-four pwCF, including 39 (61%) females, median age 18.5 (16.0, 28.5) years.  Significant increases in ppFEV1 and BMI and significant reduction in MRSA and Pseudomonas culture positivity were observed by 3 months of ETI therapy with persistent improvement through one year of treatment (p<0.001 for all).  There was also a significant reduction in the median total score using either the LM (Lund-Mackay) sinus CT scoring system (from 35 to 20) or the SL (Sheikh-Lind) sinus CT scoring system (from 23 to 13), both p<0.001. Using SL system, median total opacification parameters improved from 17 to 7 (<p<0.001 for all)

Conclusions: ETI significantly improved clinical outcomes and improved chronic sinus disease as quantified by improved sinus CT scans measured by both radiographic scoring systems.