How have CFTR modulator therapies improved cystic fibrosis disease outcomes?

Cystic fibrosis (CF) is a debilitating, life-threatening disease characterised by airway inflammation, oxidative stress, persistent airway exacerbations and abnormal lung microbiome. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and predominantly affects the lungs, gastrointestinal tract, liver and pancreas. Several drugs have been developed in the last few years to treat CF with varying degrees of success, but we still need in-depth studies of how these therapies perform over time in a wide range of patients.

• Assess longitudinal clinical outcomes, such as lung function, while using modulators
• Investigate markers of immune regulation, inflammation and iron status over time
• Investigate how CFTR therapies have changed the microbiome over time

We have collected thousands of patient samples (including whole blood, plasma, sputum, saliva and PBMCs) in a Biobank to examine disease progression and how treatment has improved patient outcomes. These samples will be analysed using techniques such as protein and gene expression studies, iron assays and sequencing to address the above aims.

This research is vital in order to contribute to the understanding of how these CFTR modulator drugs work in CF patients, how they can be changed to improve patient outcomes and potentially help to identify new therapeutic targets in the future. All this data will contribute to several papers that we hope to publish in the near future.