Extended Modulator Therapy Does Not Improve Olfactory Dysfunction in Patients with Cystic Fibrosis-Related Chronic Rhinosinusitis

by Linda Kossoff •

CLINICAL QUESTION

What is the impact of two years of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on olfactory status in patients with cystic fibrosis (CF)-related chronic rhinosinusitis (CRS)?

BOTTOM LINE

Olfactory dysfunction (OD) in adults with CF did not improve in a clinically relevant manner after two years of ETI.

BACKGROUND:  Olfactory dysfunction impacts quality of life (QOL) of individuals with chronic rhinosinusitis, a common comorbidity among people with cystic fibrosis (PwCF). ETI is a highly effective modulator that improves health, pulmonary, and CRS outcomes and extends life expectancy. The long-term effects of ETI on OD remain understudied, however.

STUDY DESIGN:  Prospective study.

SETTING: Department of Otolaryngeology-Head and Neck Surgery, University of California, Los Angeles.

SYNOPSIS: To investigate the impact of two years of ETI on olfactory status in CF-related CRS, researchers enrolled 30 adults (60% female, mean age 35.6 years) with CF-CRS who initiated ETI for clinical purposes at a single institution from August 2019–October 2020 in their study. The team used three olfactory outcome measures: 1) 40-question Smell Identification Test (SIT), 2) Questionnaire of Olfactory Disorders–Negative Statements, and 3) olfactory cleft opacification (%OCO). Data was collected at baseline (pre-ETI initiation), six months, and 24 months. A total of 28 and 26 patients completed six-month and 24-month follow-ups, respectively. Outcomes were analyzed using multivariable linear mixed effects models, including prior modulator use, sinus surgery history, age, nasal polyps, and CF-related diabetes (CFRD). After 24 months, findings showed that %OCO remained stable and SIT scores modestly worsened, suggesting that, despite highly effective therapy that improves CRS and other disease manifestations of CF, OD in adults with CF appears to be irreversible. Olfactory outcomes after ETI were not affected by prior modulator use, sinus surgery history, age, nasal polyp status, or CFRD. Study limitations included the use of a single institution setting.

CITATION: Miller JE, Oh E, Khatiwada A, et al. Two-year impact of highly effective modulator therapy on olfactory dysfunction. Laryngoscope. 2024;134:2492–2494.