COPD: 3 Biomarkers Linked to Exacerbation Risk

Diedtra Henderson

June 12, 2013

Patients with chronic obstructive pulmonary disease (COPD) who have simultaneously elevated levels of 3 key biomarkers (C-reactive protein [CRP], fibrinogen, and leukocytes) appear to have a higher risk of exacerbations than those with lower levels, according to a prospective study. The association holds true even if for patients who have a mild form of the ailment or have never before experienced such symptoms.

Mette Thomsen, MD, from the Department of Clinical Biochemistry and the Copenhagen General Population Study at Herlev Hospital and Copenhagen University Hospital in Herlev and from the Faculty of Health and Medical Sciences at the University of Copenhagen, in Copenhagen, Denmark, and colleagues present their findings in an article published in the June 12 issue of JAMA.

As COPD worsens, patients suffer frequent exacerbations that hasten loss of lung function, frequently require hospitalization, and imperil survival. Such events are often caused by respiratory tract infections, Dr. Thomsen and colleagues write, and CRP has been implicated as a smoking gun, as levels of such inflammatory cells are elevated during acute episodes. Moreover, the researchers note, levels of the trio of inflammatory biomarkers are associated with poor outcomes even for patients whose COPD is not flaring up. Therefore, they sought to determine whether elevated levels of these biomarkers correlated with a heightened risk of exacerbations.

The researchers invited 61,650 white patients who had spirometry measurements as part of the 2-year Copenhagen City Heart Study or the 5-year Copenhagen General Population Study to participate in the study. They identified 6574 participants with COPD and included them in further analyses.

"The principal finding of this study is that simultaneously elevated levels of CRP, fibrinogen, and leukocytes were associated with increased risk of frequent exacerbations in individuals with stable COPD," the authors write. "Risk of having frequent exacerbations was increased approximately 4-fold in the first year of follow-up and 3-fold using maximum follow-up time in individuals with 3 high inflammatory biomarkers compared with individuals who had no elevated biomarkers," the research team continued.

In an accompanying editorial, M. Jeffery Mador, MD, and Sanjay Sethi, MD, both from the Division of Pulmonary, Critical, and Sleep Medicine, Department of Medicine, University at Buffalo, State University of New York, Buffalo, and VA Western New York Healthcare System, Buffalo, New York, found that adding the trio of biomarkers to traditional predictive tools provided "a statistically significant improvement...of uncertain clinical significance."

Extracting more value out of the biomarkers will require "careful phenotyping of patients with COPD, using clinical and biomarker measures," Dr. Mador and Dr. Sethi write. "Thomsen et al have shown that biomarkers may hold promise for identifying high-risk patients and that assessing combinations of biomarkers, rather than a single measurement, may be needed to improve risk stratification."

Dr. Thomsen and colleagues acknowledged the need for additional study. "Further investigation is needed to determine the clinical value of these biomarkers for risk stratification."

Financial support for this study was provided by the Herlev Hospital, Copenhagen University Hospital, the Danish Heart Foundation, the Copenhagen County Foundation, and the University of Copenhagen. Dr. Mador has disclosed receiving grants from the National Institutes of Health and GlaxoSmithKline. The authors and Dr. Sethi have disclosed no relevant financial relationships.

JAMA. 2013;309:2353-2361. Article abstract, Editorial extract

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