Elevated inflammatory biomarkers linked with increased risk of COPD exacerbations

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1. Elevated levels of CRP, fibrinogen, and leukocyte count are associated with an increased risk of COPD exacerbations over one year.

2. There was a stepwise increase in the risk of frequent exacerbations over the 1, 3, and 5 year follow-up period based upon the number of biomarkers present.

Evidence Rating Level: 2 (Good)

Study Rundown: This study showed that the combination of elevated levels of C-reactive protein (CRP), fibrinogen, and leukocyte count was associated with a stepwise increased risk of chronic obstructive pulmonary disease (COPD) exacerbations, even in patients with mild disease. The present study is the first study to demonstrate the association between all 3 different inflammatory biomarkers and the risk of frequent COPD exacerbations.

There are several limitations to the study which must be addressed with further research before these biomarkers are used in everyday clinical practice. First, the study includes more mild to moderate COPD cases relative to severe cases, and further validation may be warranted for all subsets of COPD patients. Furthermore, it is possible that there may be omitted cases of mild COPD that were misdiagnosed as acute bronchitis, which could affect the study’s interpretation of inflammatory biomarkers. Nonetheless, this prospective cohort study was well executed and may herald a greater use of inflammatory markers in the management of COPD patients if further studies may validate the findings of this study.

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Relevant Reading: Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease: GOLD executive summary

In-Depth [prospective, cohort study]: This study selected 8,020 individuals from 2 general population studies in Copenhagen, stratified according to age and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4 and A-D. Plasma levels of high sensitivity CRP, fibrinogen, and whole blood leukocyte count were measured, along with exacerbations. Over the first year of follow-up, the odds ratio for frequent exacerbations were 1.5, 2.6, and 6.4 for the 3 respective groups compared to patients without elevated biomarkers (p= 3×10-11). Among 3 groups in comparison to patients without elevated biomarkers, hazard ratios for having at least 1 exacerbation were 1.2, 1.3, and 1.8 (p=2×10-7), respectively. A similar stepwise increase in frequency was seen in the absolute 1 year, 3 year, 5 year risk of frequent exacerbations from none to 3 elevated biomarkers across all GOLD grades A-D, 1-4, and those with history of frequent exacerbations.

By Elizabeth Park and Rif Rahman

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