Elexacaftor-tezacaftor-ivacaftor (ETI) improves pulmonary health and chronic rhinosinusitis (CRS) for people with cystic fibrosis (PwCF), however its impact on olfaction has not been investigated. Olfactory dysfunction impairs quality-of-life (QOL). This study evaluated the impact of ETI on multiple olfactory metrics.
Adult PwCF/CRS with CF transmembrane conductance regulator genotype F508del/F508del or F508del/minimal function who clinically initiated ETI participated in a prospective, observational study. Endpoints included changes after 6 months of ETI in quantitative olfactory function (Smell Identification Test, SIT), olfactory QOL (Questionnaire of Olfactory Disorders, QOD) and percent olfactory cleft opacification (%OCO), representing superior nasal cavity inflammation where afferent olfactory neurons are concentrated.
30 PwCF/CRS met inclusion criteria; 25 completed the study. Mean ETI adherence was 93%. At baseline, participants were hyposmic (mean SIT 31.3), had significant %OCO (mean 65.6%), yet reported non-impaired olfactory QOL (mean QOD 6.1). At follow-up, mean SIT worsened mildly (p=0.009), mean %OCO remained stable (p=0.46), and mean QOD improved modestly (p=0.008). No outcomes were impacted by prior modulator use, genotype, nasal polyps, or CF-related diabetes. Prior sinus surgery was associated with QOD improvement (p=0.04). Increased (worse) baseline QOD scores and %OCO were associated with greater improvements (p<0.003), but not SIT (p=0.44).
ETI was not associated with improvement in quantitative olfaction or olfactory cleft opacification after 6 months. PwCF/CRS have hyposmia but do not report impairment in olfactory QOL. Further study to investigate mechanisms explaining olfactory dysfunction and whether olfaction improves with greater duration of ETI or in younger age groups is warranted.

Copyright © 2021. Published by Elsevier B.V.

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