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Explore This IssueSeptember 2023
Cystic fibrosis (CF) results from a deficiency or a defect in the CF transmembrane conductance regulator protein (CFTR). Loss of function of the CFTR anion channel causes increased viscosity of secreted mucus and results in significant impairment of the sinonasal mucosa natural mucociliary clearance mechanism. It follows that a high proportion of patients with CF are diagnosed with chronic rhinosinusitis (CF-CRS) based on radiographic imaging and/or symptomatology.
Management of CF has changed significantly with the development of CFTR modulator therapy. Ivacaftor was the first commercially available CFTR modulator. Since then, multiple combination medications have been released, including lumacaftor/ivacaftor and tezacaftor/ivacaftor. Most recently, in 2019, elexacaftor/tezacaftor/ivacaftor (ETI) was released as a triple therapy. ETI has been shown to have positive effects on multiple organ systems.
Although ETI has continued to show promise in studies pertaining to CF-CRS, guidelines have not strongly endorsed administration of CFTR modulator therapy for the primary indication of CF-CRS. Instead, the most recent Cystic Fibrosis Foundation guidelines only suggest considering CFTR modulator therapy for the isolated indication of CF-CRS (Int Forum Allergy Rhinol. 2022;12:1089–1103).
This review outlines recent prospective data on the effects of ETI on CF-CRS and necessitates reconsideration of Cystic Fibrosis Foundation guidelines about this treatment.
Best current evidence regarding ETI in patients with CF and CF-CRS consists of prospective single-arm cohort studies. ETI is highly effective in improving CT findings, nasal endoscopy findings, and quality of life as measured by various patient-reported outcome measures in both patient groups; however, ETI does not appear to improve olfaction in CF-CRS.
Creating larger multicenter prospective trials in the future to confirm these conclusions is warranted. Given the recent studies outlined, it is recommended that CFTR modulator therapy not only be considered as a treatment for, but also used as a treatment for CF-CRS in patients with CF who qualify based on their age and their genotype.