Treatment with elexacaftor/tezacaftor/ivacaftor does not alter SpiroNose-derived electronic breath profiles in children with cystic fibrosis.

BACKGROUND

Breath profile analysis of volatile organic compounds (VOCs) by electronic nose (eNose) technology can distinguish between healthy individuals and people with cystic fibrosis (pwCF). It remains, however, unclear whether CFTR modulator therapy, that corrects the underlying defect in treated pwCF, alters the exhaled breath profiles.

METHODS

In this prospective longitudinal study, eNose-derived exhaled breath profiles were obtained using the SpiroNose® (Breathomix, Leiden, The Netherlands) from 61 CF children before starting therapy with elexacaftor/tezacaftor/ivacaftor (ETI), and at follow-up visits less than 3 and more than 6 months after ETI initiation. Routine clinical outcomes and airway microbiology were assessed at all visits. Twenty-six healthy controls provided single measurements. Longitudinal SpiroNose sensor data were analyzed using linear mixed-effects models and permutational multivariate analysis of variance (PERMANOVA), and exploratory mixed-effects models to test for associations with Staphylococcus aureus (SA) airway infection and clearance.

RESULTS

ETI led to improved sweat chloride concentrations, pulmonary function (ppFEV1) and BMI, but no significant changes in SpiroNose sensor signals were observed during follow-up. SpiroNose sensor signals reliably discriminated healthy controls from CF children at baseline and at follow-up on ETI, with consistent differences in multiple SpiroNose sensors. SA airway infection was captured (sensor S7), whereas SA clearance did not result in measurable changes in SpiroNose signals.

CONCLUSIONS

CFTR modulator therapy with ETI does not significantly alter eNose-derived VOC breath profiles in children with CF. The ability of the eNose to distinguish CF from healthy controls remains unchanged after ETI initiation.