Patients with cystic fibrosis (CF) and comorbid chronic rhinosinusitis (CRS) treated with CF transmembrane conductance regulator (CFTR) modulator therapy demonstrate improved symptoms, imaging, and endoscopic appearances, according to systematic review findings published in the Journal of Cystic Fibrosis.

Clinical trials have shown CFTR modulators significantly improve CF symptoms, restoring CFTR function in lower airways, and quality of life for people with CF. However, limited attention has been paid to the effect CFTR modulators on upper airways, particularly in chronic rhinosinusitis (CRS; a common manifestation of CF). Investigators therefore sought to evaluate the impact of CFTR modulator therapy on olfactory outcomes, endoscopic appearances, imaging, and symptoms in patients with CF and CRS.

The investigators conducted a systematic review to summarize the results of studies on the use of CFTR modulator therapy in individuals with CF and CRS. The review, which searched the Cochrane Library, Scopus, and PubMed databases from January 2005 to mid-February 2023, targeted studies that assessed at least 1 of the following outcomes: olfaction, sinus/nasal endoscopic appearances, sinus/nasal radiographic findings, or sinus/nasal symptoms.

The review, which ultimately included 22 studies, indicated that the treatment of chronic rhinosinusitis in CF with CFTR modulator therapy was associated with overall improvement in endoscopic appearances, imaging, and symptoms; however, the investigators stated that limited data documented the effect of CFTR modulator therapy on olfaction.

This review found evidence of an overall benefit in symptoms, imaging, and endoscopic appearances of CF CRS in response to modulator therapy but limited impact on olfaction.

The investigators found that CRS symptoms (primarily studied in adult populations) have shown improvement with elexacaftor-tezacaftor-ivacaftor (ETI) (among the newest of the CFTR modulator therapies) starting within 7 days of treatment, with benefits plateauing after 3 months of therapy.

Sino-nasal imaging improvements have been observed primarily in the first 6 months of treatment with ETI. Greater symptomatic improvement was associated with greater baseline severity and increased age.

At 6 months post-initiation of ETI therapy, no beneficial effect had been noted on smell threshold. Notably, none of the included studies directly investigated olfaction in response to ivacaftor. A single study with 4 participants identified a positive impact of ivacaftor on endoscopic appearances (nasal polyposis completely resolved in 3/4 participants). The investigators noted that the severity of endoscopic appearances was highly correlated with imaging-based severity assessment.

Review limitations include significant heterogeneity.

“This review found evidence of an overall benefit in symptoms, imaging, and endoscopic appearances of CF CRS in response to modulator therapy but limited impact on olfaction,” the study reviewers concluded. Moreover, it is uncertain whether early initiation of CFTR modulators can decrease the progression of CF CRS.

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