Comparison of arterial and venous blood biomarker levels in chronic obstructive pulmonary disease.

Emer Kelly,Victor Pinto-Plata,David L Knowlton,Amadeus Abraham,Caroline A Owen,Bartolome R Celli

doi:10.12688/f1000research.2-114.v1

Emer Kelly, Victor Pinto-Plata + Show 4 more

Open Access

https://doi.org/10.12688/f1000research.2-114.v1

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Abstract

Purpose: The development of novel biomarkers is an unmet need in chronic obstructive pulmonary disease (COPD). Arterial blood comes directly from the lung and venous blood drains capillary beds of the organ or tissue supplied. We hypothesized that there would be a difference in levels of the biomarkers metalloproteinase 9 (MMP-9), vascular endothelial growth factor A (VEGF-A) and interleukin 6 (IL-6) in arterial compared with venous blood. Methods: Radial artery and brachial vein blood samples were taken simultaneously in each of 12 patients with COPD and seven controls with normal lung function. Circulating immunoreactive MMP-9, VEGF-A and IL-6 levels in serum were measured using quantitative enzyme-linked immunosorbent assays. Results were compared using a Student’s paired t test. The study was powered to determine whether significant differences in cytokine levels were present between paired arterial and venous blood samples. Results: In the 12 patients with COPD, four were female, and age ranged 53-85 years, mean age 69 years. Three patients in the control group were female, with age range 46-84 years, mean age 64.7 years. In the COPD group, three patients had mild, five moderate and four severe COPD. No significant difference was found between arterial and venous levels of MMP-9, VEGF-A or IL-6. Conclusions: In this pilot study, levels of the measured biomarkers in arterial compared with venous blood in both COPD patients and healthy controls did not differ. This suggests that as we continue to chase the elusive biomarker in COPD as a potential tool to measure disease activity, we should focus on venous blood for this purpose.

Highlights

Chronic obstructive pulmonary disease (COPD) is a major public health issue, predicted to become the 3rd leading cause of mortality in the United States[1,2]
Our group has recently shown that serum levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF alpha) were higher and matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor (VEGF) lower in patients with severe and very severe COPD compared with smoker and nonsmoker controls without airflow obstruction[9]
As levels of IL-6 were undetectable in many of the patients, it was not possible to determine if a significant difference existed between those with COPD and the control group. This pilot study showed no difference in serum levels of MMP-9, vascular endothelial growth factor A (VEGF-A) or IL-6 between arterial and venous blood samples in a group of patients with COPD and controls without airflow obstruction

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a major public health issue, predicted to become the 3rd leading cause of mortality in the United States[1,2]. The Global Initiative for Obstructive Lung Diseases (GOLD) divides patients into categories of mild, moderate, severe and very severe based on the forced expiratory volume in 1 second (FEV1) This classification has been shown to predict outcome and has been pivotal in guiding treatment of the disease[3]. The duration of the large trials that have evaluated the effect of pharmacological or surgical benefits in patients with COPD have ranged from 2 to 4 years[4,5,6,7] It follows that defining disease activity or response to therapy with validated biomarkers that reflect disease progression would make potential future interventions easier to evaluate. While there is no question that a biomarker would be of great importance in COPD, the sample site having the greatest yield has not been clearly defined[11]

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