Bronchodilator reversibility increases in people with cystic fibrosis after initiation of Kaftrio

<bold>Background:</bold> Kaftrio (elexacaftor, tezacaftor and ivacaftor; ETI) is a highly effective Cystic Fibrosis transmembrane conductance regulatory modulator therapy for people with CF (PwCF) with a dF508 mutation. In PwCF an increase of FEV1 and FVC was observed after initiation of ETI. In some PwCF we observed increased bronchodilator reversibility (BR) in FEV1 and more symptoms of bronchial hyperreactivity (BHR). <bold>Aim:</bold> To assess the increase in bronchodilator reversibility with ETI in PwCF, before and after initiation of ETI. <bold>Method:</bold> PwCF in our outpatient clinic who started ETI in 2022 and performed BR testing as part of their annual checkup before and after initiation of ETI, were included in the analysis. FEV1, FVC and BR after 400 µg of salbutamol before ETI were compared with results after 12 months of ETI <bold>Result:</bold> 19 adult PwCF (10 male; 74% homozygous dF508 mutation) were included. One person also had asthma. All PwCF showed a significant increase of lung function after 12 months post ETI. Median (IQR) pbd FEV1 in percent predicted (pp) was 72.2 (38.2)pp pre ETI vs 89.8 (31.9)pp post ETI (p<0.001).. Mean (SD) FVC (pp) was 95±16.1pp pre ETI vs 104±17.3pp post ETI (p<0.001). Mean bronchodilator reversibility was 0.185 ± 0.16L pre ETI and 0.262± 0.14L, p=0.045 post ETI. <bold>Conclusion:</bold> A small but significant increase in bronchodilator reversibility in PwCF on ETI was found compared to before ETI. The pathophysiology behind this phenomenon and the link with <bold>increased</bold> BHR symptoms needs further research for better understanding.