What question did this study set out to answer?

This research investigates how the CFTR modulator therapy alters respiratory pathogens in children with cystic fibrosis.

April 20, 2026Open Access

Impact of elexacaftor/tezacaftor/ivacaftor on the presence of bacterial and fungal pathogens in the lower respiratory tract of children with cystic fibrosis

Key Points

This research investigates how the CFTR modulator therapy alters respiratory pathogens in children with cystic fibrosis.
Conducted a prospective observational study at a single center.
Included children aged 6-12 years starting ETI with no previous CFTR modulator exposure.
Assessed lower airway microbiology using induced sputum and evaluated several clinical outcomes.
Notable decrease in growth of methicillin-sensitive Staphylococcus aureus and Aspergillus fumigatus.
Reduced variability in fungal populations in lower airways.
Increased negative culture results for both bacterial and fungal pathogens after starting ETI.

Abstract

Background:Highly effective CFTR modulator therapy, such as elexacaftor/tezacaftor/ivacaftor (ETI), has been linked to significant clinical improvements in people with cystic fibrosis (pwCF).However, its effect on the presence of respiratory pathogens in the lower respiratory tract of younger, mainly non-expectorant children with CF remains poorly understood, especially using lower airway sampling methods.We aimed to investigate changes in lower airway microbiology and clinical outcomes in children with CF aged 6-12 years before and after starting ETI.Methods: We conducted a prospective observational single-centre study including children with CF commencing ETI who had no prior exposure to CFTR modulators, inhaled antibiotics, or prophylactic antibiotics.Lower airway microbiology was assessed longitudinally using sputum or induced sputum (IS).Pathogen prevalence, sweat chloride concentration, pulmonary function, nutritional status, and rate of exacerbations were evaluated before and up to 12 months after ETI initiation.Results: Sixteen pwCF were included (median age 8.4 years, 69 % boys, 75% were F508del homozygous).None of the children was expectorant at any point during the study.Following ETI initiation, we observed decreased growth of methicillin-sensitive Staphylococcus aureus and Aspergillus fumigatus, reduced variability in fungal populations, and an increase in negative bacterial and fungal culture results.Conclusions: In this exploratory study of young, modulator-nave children with CF, ETI initiation was associated with changes in the lower airway microbiology composition assessed by IS.These findings highlight potential shifts in lower airway microbiology and the importance of age-appropriate lower airway sampling in future paediatric studies.

Mark Helpful

Bookmark

Relay

View Full Paper