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Randomized Controlled Trial
. 2012 Jul 1;186(1):48-55.
doi: 10.1164/rccm.201108-1553OC. Epub 2012 Mar 23.

Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial

Mona Bafadhel  1 , Susan McKenna, Sarah Terry, Vijay Mistry, Mitesh Pancholi, Per Venge, David A Lomas, Michael R Barer, Sebastian L Johnston, Ian D Pavord, Christopher E Brightling
Affiliations
Randomized Controlled Trial

Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial

Mona Bafadhel et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous.

Objectives: Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations.

Methods: Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and ≤ 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms.

Measurements and main results: There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0-0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01-0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04).

Conclusions: The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.

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Figures

Figure 1.
Figure 1.
CONSORT diagram for patient enrollment and randomization. Biomarker blood eosinophil levels were measured at exacerbation in both study groups, but only in the biomarker-directed arm were biomarker levels used to direct placebo or matching prednisolone treatment in addition to antibiotic therapy. In the standard arm, all subjects received prednisolone and antibiotic therapy. Four subjects in the biomarker-directed treatment arm switched from placebo to prednisolone treatment, and two subjects switched from prednisolone to placebo. Subjects and study personnel involved in data collection and assessment of treatment failure were blinded to study group allocation, biomarker results, and treatment allocation.
Figure 2.
Figure 2.
Standard therapy group (red) and biomarker-directed therapy group (blue). (a) Chronic Respiratory Disease Questionnaire total score at baseline, exacerbation, after 14-day placebo or prednisolone treatment (2 wk after exacerbation) and recovery (6 wk after exacerbation) in standard therapy arm (n = 80) and biomarker-directed therapy arm (n = 86). Data presented as mean (SEM). (b) FEV1 at baseline, exacerbation, after 14 days of placebo or prednisolone treatment (2 wk after exacerbation) and recovery (6 wk after exacerbation) in standard therapy arm (n = 80) and biomarker-directed therapy arm (n = 86). (c) Percent improvement in visual analog scale total score from exacerbation and for duration of treatment period in exacerbations in standard therapy arm (n = 80) and biomarker-directed therapy arm (n = 86). Data points presented as mean (SEM). CRQ = Chronic Respiratory Disease Questionnaire; VAS = visual analog scale.
Figure 3.
Figure 3.
(a) Chronic Respiratory Disease Questionnaire total score at baseline, exacerbation, after 14 days of treatment (2 wk after exacerbation) and recovery (6 wk after exacerbation) in exacerbations that were biomarker-positive treated with prednisolone (green), biomarker negative treated with prednisolone (orange), and biomarker negative treated with placebo (purple). Data presented as mean (SEM). (b) FEV1 at baseline, exacerbation, after 14 days of placebo or prednisolone treatment (2 wk after exacerbation) and recovery (6 wk after exacerbation) in exacerbations that were biomarker positive treated with prednisolone (green), biomarker negative treated with prednisolone (orange), and biomarker negative treated with placebo (purple). Data presented as mean (SEM). (c) Percent improvement in visual analog scale total score from exacerbation and for duration of treatment period in exacerbations that were biomarker positive treated with prednisolone (green), biomarker negative treated with prednisolone (orange), and biomarker negative treated with placebo (purple). Data points presented as mean (SEM). CRQ = Chronic Respiratory Disease Questionnaire; VAS = visual analog scale.
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