COPD association and repeatability of blood biomarkers in the ECLIPSE cohort

Jennifer A Dickens, Bruce E Miller, Lisa D Edwards, Edwin K Silverman, David A Lomas, Ruth Tal-Singer, Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators, Yavor Ivanov, Kosta Kostov, Jean Bourbeau, Paul Hernandez, Kieran Killian, Robert Levy, Francois Maltais, Denis O'Donnell, Jan Krepelka, Jørgen Vestbo, Emiel Wouters, Dean Quinn, Per Bakke, Mitja Kosnik, Alvar Agusti, Jaume Sauleda, Yuri Feschenko, Vladamir Gavrisyuk, Lyudmila Yashina, Nadezhda Monogarova, Peter Calverley, David Lomas, William MacNee, David Singh, Jadwiga Wedzicha, Antonio Anzueto, Sidney Braman, Richard Casaburi, Bart Celli, Glenn Giessel, Mark Gotfried, Gary Greenwald, Nicola Hanania, Don Mahler, Barry Make, Stephen Rennard, Carolyn Rochester, Paul Scanlon, Dan Schuller, Frank Sciurba, Amir Sharafkhaneh, Thomas Siler, Edwin Silverman, Adam Wanner, Robert Wise, Richard ZuWallack, Harvey Coxson, Lisa Edwards, Katharine Knobil, David Lomas, William MacNee, Edwin Silverman, Ruth Tal-Singer, Jørgen Vestbo, Julie Yates, Alvar Agusti, Peter Calverley, Bartolome Celli, Courtney Crim, Gerry Hagan, William MacNee, Bruce Miller, Stephen Rennard, Ruth Tal-Singer, Emiel Wouters, Julie Yates, Jennifer A Dickens, Bruce E Miller, Lisa D Edwards, Edwin K Silverman, David A Lomas, Ruth Tal-Singer, Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) study investigators, Yavor Ivanov, Kosta Kostov, Jean Bourbeau, Paul Hernandez, Kieran Killian, Robert Levy, Francois Maltais, Denis O'Donnell, Jan Krepelka, Jørgen Vestbo, Emiel Wouters, Dean Quinn, Per Bakke, Mitja Kosnik, Alvar Agusti, Jaume Sauleda, Yuri Feschenko, Vladamir Gavrisyuk, Lyudmila Yashina, Nadezhda Monogarova, Peter Calverley, David Lomas, William MacNee, David Singh, Jadwiga Wedzicha, Antonio Anzueto, Sidney Braman, Richard Casaburi, Bart Celli, Glenn Giessel, Mark Gotfried, Gary Greenwald, Nicola Hanania, Don Mahler, Barry Make, Stephen Rennard, Carolyn Rochester, Paul Scanlon, Dan Schuller, Frank Sciurba, Amir Sharafkhaneh, Thomas Siler, Edwin Silverman, Adam Wanner, Robert Wise, Richard ZuWallack, Harvey Coxson, Lisa Edwards, Katharine Knobil, David Lomas, William MacNee, Edwin Silverman, Ruth Tal-Singer, Jørgen Vestbo, Julie Yates, Alvar Agusti, Peter Calverley, Bartolome Celli, Courtney Crim, Gerry Hagan, William MacNee, Bruce Miller, Stephen Rennard, Ruth Tal-Singer, Emiel Wouters, Julie Yates

Abstract

Background: There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.

Methods: Thirty-four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients.

Results: Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-α and interferon-γ, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved.

Conclusions: Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD). Further analysis of more promising biomarkers may reveal utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation.

Trial registration: SCO104960, clinicaltrials.gov identifier NCT00292552.

Figures

Figure 1
Figure 1
Bland Altman plots and frequency histograms of differences between baseline and 3-month results illustrating variability of selected biomarkers. All values have been log transformed prior to analysis.

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