Pseudomonas infections persisting after CFTR modulators are widespread throughout the lungs and drive lung inflammation

2025-08-13

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve the physiological defect causing cystic fibrosis, but the lungs of most people remain infected and inflamed. A leading hypothesis implicates damaged segments as the cause of persistent infection and predicts that mildly diseased segments within an individual's lungs will clear after treatment, whereas severely diseased segments will not. Our findings contradict this hypothesis. We used bronchoscopy to sample the least- and most-damaged lung segments in Pseudomonas aeruginosa (Pa)-infected individuals before modulators and returned to these same segments after 1.5 years. Surprisingly, we find an “all-or-none” infection clearance response: the most-diseased segments clear if any other lung segment in that person clears, and the least-diseased segments remain infected if others in that person do. Furthermore, neutrophilic inflammation completely resolves where Pa clears but remains elevated where Pa persists. These data indicate that post-modulator infections are not limited to severely diseased segments and that Pa infections drive persistent lung inflammation after modulators.

Open access content. Open access content
info:eu-repo/semantics/openAccess

application/pdf
English

QGQ oai:pure.eur.nl:publications/15d62a09-2524-4c3b-8e43-7795ed1aa45d
https://pure.eur.nl/en/publications/15d62a09-2524-4c3b-8e43-7795ed1aa45d
https://doi.org/10.1016/j.chom.2025.07.009
https://pure.eur.nl/ws/files/204507053/1-s2.0-S1931312825002811-main.pdf
1533989730

ERASMUS UNIVERSITEIT ROTTERDAM
From OAIster®, provided by the OCLC Cooperative.

edsoai.on1533989730