Abstract Background Elexacaftor-tezacaftor-ivacaftor (ETI) has become a mainstay in the treatment of CF patients who are at least heterozygotes for the F508del mutation. It improves pulmonary function and quality of life and reduces respiratory exacerbations. However, scarce data is available regarding its effect on lung bacterial colonization. Objectives Our objective was to assess the influence of ETI on the number of different respiratory pathogens found in patients with CF (pwCF) one year before and one year after its initiation. Our secondary objective was to compare the prevalence of Pseudomonas aeruginosa and Staphylococcus aureus in pwCF airways for the same periods. Design/Methods We conducted an observational cohort study in our CF clinic. PwCF were included if they were aged 6 to 17 years. We studied 56 patients in total after ethical approval was obtained. We calculated the mean difference between the number of different pathogens 12 months and 6 months before and after ETI. Mean differences were also calculated to compare the prevalence of Pseudomonas aeruginosa and Staphylococcus aureus for the same periods. Samples were obtained by sputum or throat cultures. We used multivariate generalized linear models, based on the generalized estimating equations (GEE) method. Models were adjusted for age, genotype, and the duration of antibiotic treatment for exacerbation or eradication. Results We found a statistically significant difference in means of 0.65 (95% CI: 0.51,0.81; p=0.002) between the number of respiratory pathogens in the year following ETI compared to the year before. Regarding Pseudomonas aeruginosa, we found a statistically significant decrease in its prevalence in the year after ETI, with an odds ratio of 0.45 (95% CI: 0.24,0.83; p=0.02). For Staphylococcus aureus, we found a non-statistically significant decrease in its prevalence after ETI with an odds ratio of 0.79 (95% CI: 0.41,1.5; p=0.47). Conclusion Our study shows a reduction in the number of bacteria in the airways of pwCF one year after ETI. It also shows a decrease in the prevalence of Pseudomonas aeruginosa and Staphylococcus aureus. These findings are consistent with the improvement seen in FEV1 and reduction of respiratory exacerbations after ETI. It will eventually be important to study its effect on the diversity of respiratory microbiota and to understand its effect on chronic lung inflammation.
Hébert et al. (Mon,) studied this question.