AUTHOR=Matthews Emma Lea , Hirsch Meghan June , Prokopczuk Federico , Jones Luke I. , Martínez Eriel , Barnes Jarrod W. , Krick Stefanie 

TITLE=Wound repair and immune function in the Pseudomonas infected CF lung: before and after highly effective modulator therapy

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1566495

DOI=10.3389/fcimb.2025.1566495

ISSN=2235-2988

ABSTRACT=The leading cause of death for people with cystic fibrosis (pwCF) continues to be due to respiratory-related illnesses. Both wound repair and immune cell responses are dysregulated in the CF airways, creating a cycle of unresolved injury and perpetuating inflammation. PwCF are predisposed to colonization and infections with opportunistic bacteria like Pseudomonas aeruginosa (Pa), the most common adult pathogen in CF. Pa possesses key virulence factors that can exacerbate chronic inflammation and lung injury. With the approval of highly effective modulator therapies like elexacaftor/tezacaftor/ivacaftor (ETI), pwCF eligible for ETI have seen drastic improvements in lung function and clinical outcomes, including an increased life expectancy. While modulator therapies are improving bronchial epithelial cellular processes in wound repair and some areas of immunity, many of these processes do not reach a non-CF baseline state or have not been thoroughly studied. The effect of modulator therapy on Pa may lead to a reduction in infection, but in more longitudinal studies, there is not always eradication of Pa, and colonization and infection frequency can return to pre-modulator levels over time. Finally, in this review we explore the current state of additional treatments for CF lung disease, independent of CFTR genotype, including anti-inflammatories, phage-therapies, and Pa vaccines.