Changes in the fungal ecology in the era of CFTR modulators: Results from a French multicentre study focused on cystic fibrosis airways

The introduction of CFTR modulator therapies (CFTRmt) has changed cystic fibrosis (CF) management. By improving airway rheology and function in people with CF (pwCF), CFTRmt are expected to modify cyto-microbiological features. This French multicentre study aimed to assess changes in airway fungal ecology before and during the CFTRmt era. Data from pwCF followed at CF reference centres in Besançon, Bordeaux, Limoges, and Rennes were collected before CFTRmt use (2014) and after their widespread implementation (2022), including elexacaftor/tezacaftor/ivacaftor (ETI) as well as other CFTR modulator therapies used in France. Mycological outcomes included the total number of yearly cultures and the number of positive cultures per fungus and per patient, regardless of CFTRmt. A total of 1555 and 1400 sputum samples from 438 and 483 pwCF were analysed in 2014 and 2022, respectively. The 2022 population was significantly older, in agreement with French ETI-prescription limited to pwCF aged at least 12 in 2022. Regardless of year, patients with positive fungal cultures were older than those with negative ones. Positive cultures for Aspergillus section Fumigati significantly decreased under CFTRmt at both population and individual levels. Conversely, positive cultures for Aspergillus section Nigri, Penicillium sp., and Candida albicans increased under CFTRmt, in correlation with the type of CFTRmt for Aspergillus section Nigri. CFTR modulators appear to modify the airway mycobiome and fungal ecology depending on CFTRmt type. Among several factors that may account for these mycobiome changes between 2014 and 2022, environmental changes, including climate-related shifts in Aspergillus distribution, may contribute potentially.