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Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials

Authors
  • Singh, Dave1
  • Wedzicha, Jadwiga A.2
  • Siddiqui, Salman3
  • de la Hoz, Alberto4
  • Xue, Wenqiong5
  • Magnussen, Helgo6
  • Miravitlles, Marc7
  • Chalmers, James D.8
  • Calverley, Peter M. A.9
  • 1 Manchester University NHS Foundation Trust, Manchester, UK , Manchester (United Kingdom)
  • 2 Imperial College London, London, UK , London (United Kingdom)
  • 3 University of Leicester, Leicester, UK , Leicester (United Kingdom)
  • 4 Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany , Ingelheim am Rhein (Germany)
  • 5 Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA , Ridgefield (United States)
  • 6 Pulmonary Research Institute at Lung Clinic Grosshansdorf, Grosshansdorf, Germany , Grosshansdorf (Germany)
  • 7 CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain , Barcelona (Spain)
  • 8 University of Dundee, Ninewells Hospital and Medical School, Dundee, UK , Dundee (United Kingdom)
  • 9 University of Liverpool, Liverpool, UK , Liverpool (United Kingdom)
Type
Published Article
Journal
Respiratory Research
Publisher
BioMed Central
Publication Date
Sep 17, 2020
Volume
21
Issue
1
Identifiers
DOI: 10.1186/s12931-020-01482-1
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation and chronic inflammation. Predicting exacerbations of COPD, which contribute to disease progression, is important to guide preventative treatment and improve outcomes. Blood eosinophils are a biomarker for patient responsiveness to inhaled corticosteroids (ICS); however, their effectiveness as a predictive biomarker for COPD exacerbations is unclear.MethodsThis post hoc analysis pooled data from 11 Boehringer Ingelheim-sponsored Phase III and IV randomised COPD studies with similar methodologies. Exacerbation data were collected from these studies, excluding patients from the ICS withdrawal arm of the WISDOM® study. Patients were grouped according to their baseline blood eosinophil count, baseline ICS use and number of exacerbations in the year prior to each study.ResultsExacerbation rate data and baseline eosinophil count were available for 22,125 patients; 45.6% presented with a baseline blood eosinophil count of ≤ 150 cells/μL, 34.3% with 150–300 cells/μL and 20.1% with > 300 cells/μL. The lowest exacerbation rates were observed in patients with ≤ 150 cells/μL, with small increases in exacerbation rate observed with increasing eosinophil count. When stratified by exacerbation history, the annual rate of exacerbations for patients with 0 exacerbations in the previous year increased in line with increasing eosinophil counts (0.38 for ≤ 150 cells/μL, 0.39 for 150–300 cells/μL and 0.44 for > 300 cells/μL respectively). A similar trend was identified for patients with one exacerbation in the previous year, 0.62, 0.66 and 0.67 respectively. For patients with ≥ 2 exacerbations, exacerbation rates fluctuated between 1.02 (≤ 150 cells/μL) to 1.10 (150–300 cells/μL) and 1.07 (> 300 cells/μL). Higher exacerbation rates were noted in patients treated with ICS at baseline (range 0.75 to 0.82 with increasing eosinophil count) compared with patients not on ICS (range 0.45 to 0.49).ConclusionWe found no clinically important relationship between baseline blood eosinophil count and exacerbation rate. Hence, the current analysis does not support the use of blood eosinophils to predict exacerbation risk; however, previous exacerbation history was found to be a more reliable predictor of future exacerbations.Trial registrationClinicalTrials.gov Identifiers: NCT00168844, NCT00168831, NCT00387088, NCT00782210, NCT00782509, NCT00793624, NCT00796653, NCT01431274, NCT01431287, NCT02296138 and NCT00975195.Graphical abstract

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