Ivacaftor Modifies Cystic Fibrosis Neutrophil Phenotype in Subjects with R117H Residual Function CFTR Mutations

CFTR modulator therapy (Ivacaftor, lumacaftor, tezacaftor) treats the basic defect in CF by increasing CFTR function and improving lung function and quality of life. CF lung disease is characterised by chronic bacterial colonisation, inflammation and excessive neutrophilia [1]. The confirmation of CFTR expression on neutrophils [2] led to speculation that immune cell dysfunction may be implicated in CF lung inflammation. Neutrophils from people with CF (PWCF) with severe CFTR mutations (e.g. F508del and G551D) have prolonged neutrophil survival [3] and decreased phagocytosis and degranulation. The residual function R117H mutation causes a 25% decrease in channel conductance [4], and when present in combination with a second severe mutation (e.g. F508del) results in CFTR function that lies somewhere between heathy controls and typical CF.