PMC5216532_01
Disease progression timeline of treatments, development of autoimmune response and clinical severity indices. a FEV1 and blood eosinophils (109/L) is plotted on the left Y axis, while sputum eosinophil % on the right Y axis for the given time points. Dotted line represents the upper-limit of normal blood eosinophil level. b Association of FEV1 and sputum anti-EPX IgG (see Additional file 1: online repository for methods) is plotted on the left Y axis, while daily prednisone dose is plotted on the right Y axis. For both, black arrow indicates intravenous solumedrol (except last indicated on Jan-16 refers to 40 mg prednisone burst, tapered down to maintenance 17.5 mg dose)
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Fig1
Methotrexate, hydroxyurea, and imatinib were not effective to wean her off prednisone (Fig. 1). By 2013, she required a daily dose of 2500 mcg fluticasone propionate, long-acting beta-2 agonists, muscarinic antagonists, and 20 mg prednisone to maintain an FEV1 of 1.76 L (65% of predicted), blood eosinophils 0.03 x 109 cells/L, and 4% sputum eosinophils (Fig. 1a). In the double-blinded trial, her FEV1 was 1.76 L at the start of the study (Feb-13) that dropped to 0.9 L at the end of the study (Aug-13), with no demonstrable steroid-sparing effect (Fig. 1a). The anti-eosinophil effect of Mepolizumab was apparent from her depleting blood eosinophil levels and her sputum eosinophils being maintained below 3% until September 2013 (Fig. 1a). FEV1 was therefore not eosinophil-driven, indicating the presence of alternative mechanisms. Furthermore, her lung function continued to deteriorate with increasing airway eosinophilia (not reflected in blood), and prednisone requirement that now doubled from a pre-study dose of 20-40 mg daily (Fig. 1b).