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

Eugene Oh; Jessa E Miller; Michelle J Lee; Anna Zemke; David Baraghoshi; Matthew J Strand; Jeremiah A Alt; Todd E Bodner; Michael Chang; Naweed I Chowdhury; Patricia H Eshaghian; Anne E Getz; Jennifer L Goralski; David A Gudis; Peter H Hwang; Ashoke Khanwalkar; Adam J Kimple; Jivianne T Lee; Douglas A Li; Jess C Mace; Jayakar V Nayak; Jonathan B Overdevest; Zara Patel; Daniella K Safatian; Rodney J Schlosser; Brent Senior; Amanda L Stapleton; Timothy L Smith; Zachary M Soler; Jeffrey D Suh; Grant A Turner; Marilene B Wang; Milene T Saavedra; Jennifer L Taylor-Cousar; Daniel M Beswick

doi:10.1002/alr.70136

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

Int Forum Allergy Rhinol. 2026 Mar 13. doi: 10.1002/alr.70136. Online ahead of print.

Authors

Eugene Oh¹, Jessa E Miller², Michelle J Lee³, Anna Zemke⁴, David Baraghoshi⁵, Matthew J Strand⁵, Jeremiah A Alt⁶, Todd E Bodner⁷, Michael Chang⁸, Naweed I Chowdhury⁹, Patricia H Eshaghian¹⁰, Anne E Getz¹¹, Jennifer L Goralski¹², David A Gudis¹³, Peter H Hwang⁸, Ashoke Khanwalkar¹¹, Adam J Kimple¹⁴, Jivianne T Lee³, Douglas A Li¹⁰, Jess C Mace¹⁵, Jayakar V Nayak⁸, Jonathan B Overdevest¹³, Zara Patel⁸, Daniella K Safatian¹⁰, Rodney J Schlosser¹⁶, Brent Senior¹⁴, Amanda L Stapleton¹⁷, Timothy L Smith¹⁵, Zachary M Soler¹⁶, Jeffrey D Suh³, Grant A Turner¹⁰, Marilene B Wang³, Milene T Saavedra¹⁸, Jennifer L Taylor-Cousar^{18

19}, Daniel M Beswick³

Affiliations

¹ University of California, Los Angeles, Los Angeles, California, USA.
² Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health, Ann Arbor, Michigan, USA.
³ Department of Head and Neck Surgery, University of California, Los Angeles, California, USA.
⁴ Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁵ Division of Biostatistics, National Jewish Health, Denver, Colorado, USA.
⁶ Department of Otolaryngology-Head and Neck Surgery, University of Utah, Salt Lake City, Utah, USA.
⁷ Department of Psychology, Portland State University, Portland, Oregon, USA.
⁸ Department of Otolaryngology-Head and Neck Surgery, Stanford Medicine, Palo Alto, California, USA.
⁹ Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹⁰ Department of Pulmonary Medicine, University of California, Los Angeles, California, USA.
¹¹ Department of Otolaryngology-Head and Neck Surgery, University of Colorado, Aurora, Colorado, USA.
¹² Department of Pulmonary Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
¹³ Department of Otolaryngology-Head and Neck Surgery, Columbia University, New York, New York, USA.
¹⁴ Department of Otolaryngology-Head and Neck Surgery, University of North Carolina, Chapel Hill, North Carolina, USA.
¹⁵ Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland, Oregon, USA.
¹⁶ Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
¹⁷ Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁸ Department of Medicine, National Jewish Health, Denver, Colorado, USA.
¹⁹ Department of Pediatrics, National Jewish Health, Aurora, Colorado, USA.

PMID: 41830161
DOI: 10.1002/alr.70136

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.

Keywords: UPSIT; chronic rhinosinustis; endoscopic sinus surgery; medical therapy of chronic rhinosinusitis; olfaction; olfactory disorders; olfactory test.

Abstract

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