P175 Changes in breathprint after start of tezacaftor/ivacaftor therapy: an eNose pilot study

Electronic nose (eNose) technology measures volatile organic compounds in exhaled breath, the so-called breathprint, which can differentiate between different lung diseases. Response to CFTR-modulators differs between people with cystic fibrosis (pwCF). This pilot study assessed whether there is a change of breathprint in pwCF after starting tezacaftor/ivacaftor (TI) and if so, whether this change differs between responsive and non-responsive pwCF, as shown by spirometric improvement. In this prospective observational study, CFTR-treatment naive pwCF with residual function mutations underwent eNose measurements at baseline and one month after starting TI. Healthy controls (HCs) were also measured. Patients were labelled responsive if an increase of ≥5% of the percent predicted FEV1 occurred at one month after start of TI. The eNose data was analysed using partial least squares discriminant analysis (PLS-DA) and receiver operating characteristic (ROC) analysis. In total 32 participants were enrolled in this study, 13 pwCFand 19 HCs. PLS-DA resulted in a visual representation of discrimination between the eNose measurements. ROC analysis using all measurements as training set resulted in ROC-curves with an AUC of 0.80 (95% CI: 0.62–0.98) for the baseline measurements vs. the one-month measurements, an AUC of 0.87 (95% CI: 0.75–0.99) for the baseline measurements vs. the HCs and an AUC of 0.98 (95% CI: 0.94–1.00) for the one-month measurements vs. the HCs. After one month of TI therapy, 8 of the participants were labelled as responsive and 5 were labelled as non-responsive. Both at baseline and after one month there was no clear visual separation between responsive and non-responsive pwCF. There is a difference in breathprint between pwCF and HCs and between pwCF before and after start of TI. However, the eNose could not differentiate between responsive and non-responsive pwCF. More results will be presented at the conference.