Breath profiles in cystic fibrosis children treated with CFTR modulators

Abstract

<b>Background:</b> Exhaled breath profiles (BPs) differ between patients with cystic fibrosis (CF) and healthy controls (HC). It is not known whether these differences are caused by airway colonization with CF pathogens or other factors. <b>Aims and objectives:</b> To investigate whether electronic nose (eNose) BPs of HC were different from a) CF patients with negative airway microbiology or b) CF patients treated with CFTR modifier therapy. <b>Methods:</b> In this cross-sectional observational study, BPs were collected from clinically stable paediatric CF patients attending routine CF clinic for follow-up and compared to age-matched HC. A cloud-connected eNose, SpiroNose (de Vries et al. 2018 ERJ) was used for BP analysis. Data-analysis involved advanced signal processing, ambient correction and statistics based on linear discriminant analysis and ROC analysis. <b>Results:</b> 100 clinically stable children with CF were included (median ppFEV1 91%, age 12.0 years). The eNose was able to distinguish between HC (n=25) and all CF (accuracy 96.0%, AUC 0.985, 95%CI 0.966-1) as well as HC and CF patients with usual airway flora (n=20) (91.1%, AUC 0.994, 95%CI 0.979-1). BPs of 30 patients on CFTR modulator therapies (7 ivacaftor, 9 ivacaftor/lumacaftor, 5 ivacaftor/tezacaftor, 9 ivacaftor/tezacaftor/elexacaftor) were also different from HC (94.5%, AUC 0.999, 95%CI 0.994-1). There was no difference in BPs between CF patients treated or not treated with CFTR modulators. <b>Conclusions:</b> Differences in BPs between CF and HC cannot be explained by airway colonization with CF pathogens and CFTR modulator therapy does not seem to normalize BPs.&nbsp;Further studies are needed to identify other factors contributing to the unique BPs of people with CF.