Corticosteroid use and increased CXCR2 levels on leukocytes are associated with lumacaftor/ivacaftor discontinuation in cystic fibrosis patients homozygous for the F508del CFTR mutation
Fig 3
CXCR2 and CD63 expression on circulating leukocytes.
Flow cytometry was employed to measure the cell surface expression of CXCR2 (AF) and CD63 (GI) on circulating CD14+ CD16- monocytes (A, D, G), neutrophils (B, E, H), and NK cells (C, F, I) from non-CF and CF subjects who continued (cont.) or discontinued (stop) luma/iva use. All values are median fluorescence intensity (MFI). For the values from subjects who discontinued use, gray circles denote values from subjects who discontinued due to pulmonary adverse effects, a red triangle denotes values from a subject who developed pericarditis, a cyan diamond denotes values from a subject who experienced severe diarrhea, and a yellow square denotes values from a subject who experienced severe abdominal pain. CXCR2 levels on monocytes (A) were significantly different between the CF groups (P = 0.012 by two-tailed Mann-Whitney U test). Frequency distribution analyses (via contingency tables) was performed on CXCR2 data to determine optimal threshold levels (T, dotted lines) for distinguishing individuals who continued drug treatment from those who discontinued. Utilizing CXCR2 as a dichotomous variable (above or below threshold) improved the significance of identifying treatment discontinuation (DF) as CF subjects who discontinued were predominantly above the threshold levels (two-tailed P values by Fisher’s exact test). n≥7 for both CF groups and n = 5 for non-CF controls.