Functional, Cohort-Level Assessment of CFTR Modulator Responses Using Biobanked Nasal Epithelial Cells from Individuals with Cystic Fibrosis.

Background/

Objectives

Individual responses to CFTR modulators vary widely among people with cystic fibrosis (pwCF), underscoring the need for functional approaches that provide biological context alongside genotype-based therapy selection. Nasal epithelial cultures provide an individual-specific model for theratyping, but most studies rely on freshly isolated cells, restricting repeated testing and long-term sample use. In this study, we tested whether CFTR modulator responses measured in biobanked nasal cells were associated with real-world clinical outcomes.

Methods

Cryopreserved nasal epithelial cells from 23 pwCF were differentiated at the air-liquid interface and assessed for CFTR modulator-responsive ion transport using Ussing chambers. In vitro responses were correlated with 6-month changes in sweat chloride concentration (SCC), FEV1, and BMI.

Results

Cryopreserved cultures retained donor-specific CFTR modulator responsiveness. Modulator-induced forskolin/IBMX-stimulated currents correlated with changes in SCC (R = -0.512). CFTR inhibitor-sensitive currents correlated with FEV1 (R = 0.564). Associations between forskolin/IBMX-stimulated currents and FEV1 were positive but did not reach statistical significance using two-tailed analysis. BMI changes showed no significant association.

Conclusions

Biobanked nasal epithelial cultures preserve clinically relevant CFTR modulator responses at the cohort level, supporting their use as functional assays for population-level assessment in cystic fibrosis. This cryopreservation-based strategy enables repeated testing and may expand access to theratyping beyond freshly obtained samples.