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Published on: October 22, 2014
COPD association and repeatability of blood biomarkers in the ECLIPSE cohort
Jennifer A Dickens1, Bruce E Miller, Lisa D Edwards
1Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
Insights
Fibrinogen shows potential as a repeatable biomarker for chronic obstructive pulmonary disease (COPD) management. Further research is needed to confirm its utility in diagnosing and managing COPD patients.
Area of Science:
- Pulmonary Medicine
- Biomarker Discovery
- Clinical Trials
Background:
- Chronic obstructive pulmonary disease (COPD) requires better biomarkers for characterization and therapeutic development.
- A panel of blood biomarkers was evaluated in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort.
Purpose of the Study:
- To assess a panel of blood biomarkers for their potential utility in characterizing COPD.
- To identify repeatable and clinically relevant biomarkers for COPD diagnosis and management.
Main Methods:
- Thirty-four blood biomarkers were analyzed in 201 COPD subjects and 74 controls from the ECLIPSE cohort.
- Biomarker repeatability was assessed over 3 months, and intergroup comparisons were made using ANOVA.
- Correlations with clinical characteristics were examined using Spearman coefficients.
Main Results:
- Fifteen biomarkers differed significantly between COPD subjects and controls.
- Fibrinogen demonstrated the highest repeatability and correlated weakly with COPD severity indicators.
- Elevated CRP, fibrinogen, IL-6, and SP-D were observed in COPD subjects with recent exacerbations.
Conclusions:
- Few assessed biomarkers may aid COPD diagnosis or management based on airflow obstruction (GOLD criteria).
- Fibrinogen emerged as a promising, repeatable biomarker for COPD, warranting further investigation.
- Additional analysis of promising biomarkers could reveal utility in specific COPD patient subsets.
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.
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