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Author
Eugene Oh -
Discovery PI
Daniel M. Beswick
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Project Co-Author
Janice J. Chung, Michelle J. Lee, Jakob L. Fischer, Jason C. Woods, Edith T. Zemanick, Rhea Churi, Rachael Buckingham, Sean B. Fain, Deborah Froh, Sonya L. Heltshe, Lucas R. Hoffman, Stephen M. Humphries, Elizabeth L. Kramer, Michael Lewis, Douglas A. Li, Jaime Mata, Sarah S. Milla, Peter J. Niedbalski, Katie L. Ode, Bonnie Ramsey, Benjamin D. Sawatzky, Jillian S. Sullivan, Andrew T. Trout, Myung Shin Sim, Christopher H. Goss, Jennifer L. Taylor-Cousar
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Abstract Title
Early Modulator Therapy Improves Olfaction and Sinonasal Inflammation in Young Children with Cystic Fibrosis
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Discovery AOC Petal or Dual Degree Program
Basic, Clinical, & Translational Research
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Abstract
Background:
Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent in cystic fibrosis (CF) and negatively impact quality of life (QoL). While modulator therapy such as elexacaftor/tezacaftor/ivacaftor (ETI) improves pulmonary and CRS outcomes, it has not improved OD in adults. The impact of early ETI on olfaction in children remains unknown.Objective:
To assess changes in olfactory function and sinonasal imaging in young children with CF after one year of ETI and explore associations with caregiver-reported QoL.Methods:
In this prospective, multi-center study (May 2023-December 2024), children aged ≤9 years with CF were enrolled across six U.S. pediatric centers. Baseline and 1-year data included sinus MRI, clinical/demographic information, Pediatric Smell Wheel (PSW) testing, and caregiver QoL surveys including the Brief Questionnaire of Olfactory Disorders (BQOD), Sinonasal-5 (SN-5), and EuroQol 5 Dimensions for Youth (EQ-5D-Y). MRI-derived measures included sinus volume (SV), sinus opacification (SO), olfactory bulb volume (OBV), olfactory cleft opacification (OCO), and Lund-Mackay (LM) scores.Results:
Thirty-one participants (mean±SD age 4.8±1.9 years; 54.8% female; 100% White) were enrolled. At baseline, the mean±SD SV was 24175.2±8471.2 mm3, SO was 65.5±16.0%, OBV was 46.0±10.8mm3, OCO was 25.6±19.2%, and LM score was 9.6±4.9. PSW averaged 6.1±2.2, below the mean reported for age-matched healthy children (6.9). Twenty-one participants initiated ETI and were reassessed after an average of 12.3 months. After ETI, mean SO decreased by 25.6% (p=0.001), OCO decreased by 14.4% (p=0.004), and OBV increased by 7.4mm3 (p=0.02). Mean PSW scores improved by 1.3 points (p=0.03). QoL scores were near-normal at baseline and remained stable at follow-up.Conclusion:
Young children with CF have sinonasal opacification and OD at baseline. After one year of ETI, improvements were seen in olfactory identification, OBV, and sinonasal opacification. QoL remained near normal. These findings suggest early ETI may improve objective sinonasal and olfactory measures, unlike in adults, and support the role of imaging in detecting subclinical disease in young children with CF.