S21-- Impact of Inflammation & Infection on CFTR Function & Rescue

CF is caused by mutations in the CFTR gene, which encodes an ion channel essential for maintaining proper hydration of airway surfaces. Impaired CFTR function leads to thickened mucus, defective mucociliary clearance, and chronic bacterial infection, which in turn drives sustained airway inflammation and progressive lung damage. In the era of highly effective CFTR modulator therapies (HEMT), people with CF (pwCF) are experiencing meaningful improvements in lung function, infection burden, and inflammation. However, persistent airway infections and residual inflammation remain important clinical challenges.

Emerging evidence suggests that the relationship between CFTR rescue and infection and inflammation is not unidirectional. Airway infection and the resulting inflammatory environment can directly influence CFTR expression, function, and responsiveness to CFTR-targeting therapies. Thus, infection-driven inflammation not only shapes disease progression but also treatment responses.

This session will explore how persistent infections, host immune responses, and inflammatory signaling intersect with CFTR biology and CFTR-targeting therapies, including HEMT and nonsense mutation rescue. Understanding this interplay is critical for optimizing treatment strategies and improving outcomes for pwCF.

Presentation Order:

1. Persistent Infection After CFTR Modulator Treatment Drives Ongoing Lung Inflammation – Presented by Samantha Durfey

2. Pseudomonas Aeruginosa Affects Host Immune Response and CFTR Function – Presented by Bruce Stanton

3. Inflammation Enhances CFTR Modulator Responses – Presented by Martina Gentzsch

4. Inflammation Improves Rescue of CFTR With Nonsense Mutations – Presented by Anna Borrelli