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.\n\nFootnotes \n\nThis manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.\n\nConflict of interest: Dr. Hardisty has nothing to disclose.\n\nConflict of interest: Dr. Law has nothing to disclose.\n\nConflict of interest: Dr. Carter has nothing to disclose.\n\nConflict of interest: Brenda Grogan has nothing to disclose.\n\nConflict of interest: Dr. Singh reports grants from Vertex, during the conduct of the study.\n\nConflict of interest: Dr. Mckone reports grants from Vertex, during the conduct of the study; personal fees from Vertex Pharmaceuticals, outside the submitted work.\n\nConflict of interest: Dr. Gray reports personal fees from Vertex Pharmaceuticals, outside the submitted work.