Objectives The highly effective CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) improves CFTR function and clinical outcomes. A decrease in culture-based detection of P.aeruginosa (PA) and S.aureus (SA), but also persistent PCR detection of the pathogens present before treatment was described. The objective of our study was to determine if ETI improved microbiological outcomes overtime. We hypothesized that positive cultures would decrease overtime. Methods Sputum cultures and throat swabs were prospectively collected in all people with CF (pwCF) treated with ETI in Verona CF center; also, samples of the 12 months before the start of ETI were extracted from our records. Only pwCF with at least 24 months of follow-up were included. Total yearly positivities for of each pathogen was divided by the number of samples collected yearly on that patient. Results We included 384 pwCF (F 53.9%, mean age 31.2 ±13.8, F/F genotype 32.5%), treated with ETI for mean 32.2 (±9.7) months.PA was less frequently isolated during ETI, in comparison to the year before ETI. No significant change was seen during ETI treatment. This trend was seen also when considering adult pwCF (n. 309), while no difference in PA finding was found among children (n. 75).Non colonized rate of pwCF increased progressively during ETI, while chronically colonization and intermittently colonized decreased. Conclusions Improvements in respiratory culture positivity for PA were seen since the first year of treatment. PwCF with intermittent colonization seem less likely to clear than chronically colonized pwCF. Since initiation of ETI leads to decreased sputum availability, this may impact upon microbiological analyses. Continued microbiological monitoring in subjects on ETI is crucial despite the improvement in their overall health.

Conclusions: CFTR expression occurs in the clear and ductal cells of the ESG, and CFTR functions on the apical and basolateral cell surfaces, consistent with prior findings [2].Our approach suggests that skin punch biopsies are a minimally invasive technique for studying CFTR expression and function in ESGs of individuals with CF and CF-related diseases.