Impact of CFTR modulators on chronic and intermittent bronchial infection

<bold>Background:</bold> Sputum microbiology influences the prognosis of lung disease in people with CF. As CFTR modulators change the bronchial microenvironment, we studied the effect of the introduction of CFTR modulators on intermittent and chronic bacterial, mycobacterial and fungal bronchial infection. <bold>Aim:</bold> The aim is to investigate the microbiological influence of CFTR modulators on bronchial infection rates. <bold>Methods:</bold> It is a monocentric, retrospective study in which we collected all CF recognized pathogens in the sputa and clinical outcomes (number of exacerbations, FEV1, BMI, sex, age, genotype) in patients with CF treated by CFTR modulators, the year before, until one year after the initiation of the treatment. <bold>Results</bold>: We analyzed 136 patients (56 females) treated by all type of CFTR modulators (ivacaftor (I), lumacaftor-ivacaftor (LI), tezacaftor-ivacaftor (TI) and elexacaftor-tezacaftor- ivacaftor (ETI). Median age was 21.5y (IQR: 14-34), median BMI was 20.75kg/m² (IQR: 17.33-23.78), median FEV1 was 90%PV (IQY: 67-100), median exacerbations/year was 2 (IQR: 1-3). Patients treated by ETI after one year had a statistically significant reduction of Pseudomonas aeruginosa chronic infection (17/136 versus 8/136, p=0.0027) and Aspergillus fumigatus chronic (9/136 versus 2/136, p=0.0082) and intermittent infection (14/136 versus 5/136, p=0.0067). Following I, LI and TI, patients had no reduction of chronic nor intermittent infection of the airways. All CFTR modulators increased FEV1, only LI, TI, ETI improved BMI and TI and ETI reduced exacerbation rates. <bold>Conclusions:</bold> We showed that ETI but no other CFTR modulators influenced favorably chronic bacterial infection and chronic and intermittent fungal infection.