CFTR modulator therapy does not alter breath profiles in cystic fibrosis

<bold>Background:</bold> Electronic nose (eNose) technology can be used to detect volatile organic compounds (VOCs) in exhaled breath. eNose-generated breath profiles in people with cystic fibrosis (CF) differ from those of healthy controls, but the underlying reasons for these differences are incompletely understood. <bold>Aims and objectives:</bold> To study the effect of CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) on eNose breath profiles in CF children. <bold>Methods:</bold> In this longitudinal observational study, eNose-generated breath profiles were obtained from CF children at stable clinic visits before and after initiation of ETI therapy. A cloud-connected eNose (SpiroNose, de Vries et al. 2018 ERJ) was used for VOC measurements. Data-analysis involved advanced signal processing and ambient correction. The breath profiles were compared between the study visits by means of independent sample t-tests internally validated by 1000 iterations of bootstrap. <bold>Results:</bold> Fifty-four children with CF (F508del/F508del n=35; F508del/minimal function n=19) were included (median age 13.6 (IQR 10.1-16.5) years, percent predicted (pp)FEV1 92.0 (IQR 79.3-101.3), BMI 18.5 (IQR 16.4-20.5) m2/kg). ETI therapy (median follow-up time 7.4 (IQR 4.4-11.6) months) resulted in improvement of ppFEV1 (+10.2%; p<0.001) and BMI (+0.94 kg/m2; p<0.001), but no change in VOC breath profiles. Subgroup analysis by CFTR genotype showed no differences in breath profiles. <bold>Conclusions:</bold> CFTR modulator therapy with ETI, while improving pulmonary function and nutrition status in CF children, does not result in eNose-detectable changes of VOC composition in breath. Further studies are needed to identify factors contributing to the unique VOC breath profile of people with CF.