Determining the Minimal Clinically Important Difference of the 40-Item Smell Identification Test in People With Cystic Fibrosis

Abstract

Background

Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are highly prevalent among people with cystic fibrosis (PwCF) and negatively impact quality of life. The 40-item Smell Identification Test (SIT) is widely used to assess psychophysical olfaction, but a CF-specific minimal clinically important difference (MCID) has not been established. This study aimed to determine the SIT MCID in PwCF treated with elexacaftor/tezacaftor/ivacaftor (ETI) and/or endoscopic sinus surgery (ESS).

Methods

Data from three prospective, multi-institutional observational studies were pooled. Participants were ≥12 years old with confirmed CF and CRS who completed SIT at baseline and ≥1 follow-up (3, 6, 9, 12, or 24 months). Distribution-based MCIDs were calculated using four methods: standard error of measurement (SEM), minimal detectable change (MDC = 1.96 × SEM), 0.5 × baseline standard deviation (SD), and 0.5 × SD of change scores (ΔSD).

Results

A total of 122 participants were enrolled (mean age 32.9 years, 54% female). Of these, 99 contributed follow-up SIT scores (79 ETI, 20 ESS). SIT scores remained stable with ETI, with a small but statistically significant decline at 6 months (−1.4, p = 0.02). ESS was associated with mean gains of 3.1–4.5 points at early follow-up, though these did not reach significance. Pooled distribution-based MCID estimates ranged from 2 to 4 points, with an overall threshold of 3.1 (95% CI: 2.1–4.1).

Conclusions

This CF-specific SIT threshold provides a clinically interpretable cut-off for assessing olfaction. These findings establish a foundation for future work and highlight the importance of developing disease-specific MCIDs to guide clinical care and research.