|Title:||Impact of Elexacaftor/Tezacaftor/Ivacaftor on airway inflammation and clinical outcomes in Patients with Cystic Fibrosis.|
|Author(s):||M.Casey C.Gabillard-Lefort O.Kerr E.Marron AM.Lyons L.Cullen A.Murphy C.Gunaratnam EP.Reeves NG.McElvaney|
|Institution:||1 The Irish Centre of Genetic Lung Disease, Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland 2 Cystic Fibrosis Unit, Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland|
|Poster:||Click to view poster|
|Category:||CF and Pulmonary Infections|
|Abstract:||Current advances in therapeutics for Cystic Fibrosis(CF) include genotype-specific therapies, focused on restoring the defective CFTR protein expression and functionality, the most recent of which is Elexacaftor/Tezacaftor/Ivacaftor(Elex/tez/Iva). The clinical benefits have been well demonstrated, with little known regarding their impact on other aspects of CF pathophysiology in particular airway inflammation. We aimed to assess the impact of Elex/Tez/Iva on airway inflammatory markers in sputum samples of patients with CF (PWCF) collected pre- Elex/Tez/Iva and 3 months post.|
We evaluated 14 paired samples from PWCF, Sputum samples were processed via the TETRIS method. We measured differential cell count by light microscopy, ATP via bioluminescence, cytokines via ELISA and active neutrophil elastase(NE) via FRET assay.
We observed a mean increase in FEV1 of 13.57% (p<0.001) and in body weight of 4.14kg (p<0.001) and a reduction in CF ABLE score (p=0.0058). This clinical improvement was associated with a decrease in sputum ATP level(p<0.0001),neutrophil count(p=0.0043), IL-8(p=0.039), IL-1β(p=0.0023), TNF-R1(p=0.044) and NE (p=0.0023).
Our study demonstrates a significant impact on CF airway inflammatory markers at 3 months post treatment with an improvement in clinical parameters in keeping with published literature. We aim to assess whether this impact is sustained at 1 year and whether there is any association with a change in airway microbiota.