Fig 1.
Schematic overview of patient recruitment from the Colorado Adult CF program.
Table 1.
Baseline patient characteristics, and diagnostic and treatment history for the year prior to luma/iva initiation.
Table 2.
Patient clinical history for the year prior to luma/iva initiation stratified by adverse effects.
Fig 2.
Unadjusted odds ratios (OR) of all recorded clinical parameters associated with treatment discontinuation due to pulmonary adverse effects.
Unadjusted odds ratios (OR), lower (-95%) and upper bounds (+95%) of 95% confidence interval and P values are shown. Variables are sorted from higher to lower influence for distinguishing individuals who discontinued treatment due to pulmonary adverse effects as indicated by smaller to greater P values. Significant parameters are highlighted in bold. BMI, body mass index; CFRD, CF-related diabetes; ppFEF25-75, forced expiratory flow at 25–75% of the pulmonary volume in percent predicted; ppFEV1, forced expiratory volume in first second in percent predicted; IV Ab, exacerbation requiring intravenous antibiotics; NTM, non-tuberculous mycobacteria; OR, odds ratio; PA, Pseudomonas aeruginosa; PMN, circulating neutrophils; Pred/bud, oral prednisone and/or nasal budesonide.
Table 3.
Logistic regression model for distinguishing individuals who discontinued treatment due to pulmonary adverse effects employing clinical parameters.
Table 4.
Adjusted odds ratios (OR) of clinical parameters included for most accurate designation of subjects discontinuing treatment due to pulmonary adverse effects.
Table 5.
Baseline patient characteristics, diagnostic and treatment history for the year prior to luma/iva initiation.
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.
Table 6.
Logistic regression model for distinguishing individuals who discontinued treatment combining clinical and molecular parameters.
Table 7.
A regression model combining clinical and molecular markers accurately distinguishes individuals who discontinued luma/iva treatment in our patient cohort.