Domain‐Specific Olfaction in Children and Adults in the Era of Modulator Therapy for Cystic Fibrosis

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BACKGROUND: Little is known about when people with cystic fibrosis (PwCF) begin to experience olfactory decline, or whether sustained use of novel highly effective modulator therapies (HEMT) is predictive of better olfaction. This study evaluated psychophysical olfactory performance and HEMT-associated olfactory outcomes in children and adults with CF. METHODS: In this cross-sectional installment of a longitudinal study, individuals with a physician-confirmed diagnosis of CF completed questionnaires and psychophysical olfactory assessment (i.e., standardized assessment of olfactory domains involving a battery of olfactory stimuli). HEMT consisted of either elexacaftor-tezacaftor-ivacaftor (ETI) or vezacaftor-tezacaftor-deuivacaftor (VTD). Analysis compared performance between pediatric versus adult cohorts and assessed the impact of HEMT on psychophysical olfactory performance while controlling for age, sex, genotype, and history of sinus surgery. RESULTS: Individuals < 21 years old had better psychophysical olfactory performance than those ≥ 21 years old (61% vs. 24% normosmia). Younger age at the start of HEMT was not associated with lowered odds of threshold hyposmia [OR: 0.73; 95% CI: (0.34, 1.50)] or identification hyposmia [OR: 0.67; 95% CI: (0.35, 1.22)] within this cohort. CONCLUSION: Younger people with CF appear to have relatively preserved psychophysical olfactory function that appears to prematurely decline through early adulthood compared to the general population. Although younger age at the start of HEMT therapy was not associated with better olfactory outcomes, future prospective longitudinal studies could evaluate individuals' olfaction across their lifespan to assess the full impact of HEMT on olfaction.

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