Impact of CFTR modulator therapy in the Cystic Fibrosis microbiome - a retrospective study

<bold>Background:</bold> Cystic fibrosis (CF) respiratory tract typically harbors complex microbial communities. CF microbiome regulates clinical management and lung disease progression. The advent of CFTR modulators drastically changed CF treatment; however, little is known about the effect of these therapies on airway microbiome. <bold>Aim:</bold> To understand whether CFTR modulator therapies modify CF microbiome regarding <italic>Pseudomonas aeruginosa</italic>, <italic>Staphylococcus aureus</italic>, <italic>Haemophilus influenzae</italic> and <italic>Aspergillus fumigatus</italic>. <bold>Methods:</bold> This is a single-center and retrospective study carried out in a Portuguese CF reference center that included all CF adult patients on CFTR modulator therapy over a one year period. Sputum cultures of patients on CFTR modulator therapy were analyzed for the presence of four of the most common microorganisms: <italic>P. aeruginosa</italic>, <italic>S. aureus</italic>, <italic>H. influenzae</italic> and <italic>A. fumigatus</italic>. A comparison with sputum cultures of the same patients before starting CFTR modulator therapy was then assessed. <bold>Results:</bold> 26 CF adult patients were included. 15 (57.7%) were female and the median age was 27.5 years (IQR 18). 46.2% were homozygous for the F508del mutation and 19.2% had the genotype F508del/R334W. Differences in culture identification were not statistically significant for the germs analyzed: <italic>P. aeruginosa</italic> (X²=0.500, p=0.500), <italic>H. influenzae</italic> (X²=0.000, p=1.000), <italic>S. aureus</italic> (X²=3.125, p=0.070) and <italic>A. fumigatus</italic> (X²=0.800, p=0.375). <bold>Conclusion:</bold> There were no statistically significant differences in the microbiome of CF patients on CFTR modulator therapy regarding <italic>P. aeruginosa</italic>, <italic>H. influenzae</italic>, <italic>S. aureus</italic> and <italic>A. fumigatus</italic>.