Despite the clinical benefits of CFTR modulators , a marked variability in the responses to these drugs and their effects on airway inflammation and infections exists, indicating that our knowledge on how CFTR modulators change airway inflammation and what are the effects is incomplete.
The aim of this project is to understand what are the effects, mechanisms, and interactions of elexacaftor-tezacaftor-ivacaftor (ETI) on resolution of inflammation and infections in CF.
The premises are that aberrant and misdirected lung inflammation can arise from basic CFTR defects and can be amplified by the inability to produce molecules that curb inflammation, called SPM.
The hypothesis here is that CFTR modulators augment endogenous levels of SPM that in turn reduce and “re-educate” inflammation to make it be protective (for instance against bacteria) for people with CF.
To test this hypothesis and reach this important goal, researchers will analyze cells, proteins, and SPM in airway samples from people with CF under therapy with ETI; they will also measure concentrations of ETI in airway fluids to assess whether the effects are related to concentrations reached in the airways and are dependent on CFTR improvement.
Results from this project will help clinicians to understand better the changing medical needs of people with CF and help them to give better treatment strategies.