HealthDay News —  Elevated levels of certain inflammatory biomarkers correlate with an increased risk for disease exacerbations among patients with chronic obstructive pulmonary disease, study findings suggest.

Among study participants who had elevated levels of three high inflammatory biomarkers — C-reactive protein [CRP], fibrinogen and leukocyte count — risk for frequent exacerbations was increased approximately fourfold higher in the first year of follow-up and threefold higher using maximum follow-up time, compared with individuals who had no elevated biomarkers, according to Mette Thomsen, MD, from the Copenhagen University Hospital in Denmark, and colleagues.

“Simultaneously elevated levels of CRP and fibrinogen and leukocyte count were associated with increased risk of exacerbations in stable COPD, even for individuals with milder COPD and for those without previous exacerbations,” they reported in the Journal of the American Medical Association.

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The researchers conducted a prospective cohort study involving 61,650 participants in the Copenhagen City Heart Study and the Copenhagen General Population Study, who had spirometry measurements available. Overall, 6,574 patients with COPD were included in the final analysis. The researchers identified 3,083 exacerbations, for an average of 0.5 exacerbations per participant, during the median four year follow-up period.

In the year prior to examination, 244 individuals (4%) had one or more COPD exacerbations and 85 (1%) had their most recent exacerbation within two months of the examination date. In the first year of follow up, 129 participants had frequent COPD exacerbations (defined as two or more episodes).

Odds ratios for having frequent exacerbations in the first year of follow-up were 1.2, 1.7, and 3.7, respectively, for those with one, two and three elevated biomarkers, compared to those with no high biomarkers (trend: P=2 × 10−5), results of a multivariate-adjusted analysis revealed.

“The number of individuals with frequent exacerbations increased stepwise according to groups of inflammatory biomarkers,” the researchers wrote.

The number of COPD exacerbations in relation to biomarker presence was as follows:

  • No elevated biomarkers (N=3,293) — 9 per 1,000 person years (95% CI: 6.6-13)
  • One elevated biomarker (N=1,831) — 17 per 1,000 person years (95% CI: 12-25)
  • Two elevated biomarkers (N=1,066) — 32 per 1,000 person years (95% CI: 24-46)
  • Three elevated biomarkers (N=384) — 81 per 1,000 person years (95% CI: 59-120)

At maximum follow-up, the corresponding hazard ratios were 1.4, 1.6 and 2.5 (trend: P = 1 × 10−8). For those with milder COPD and those with no history of exacerbations, the relative risks were consistent.

“Further investigation is needed to determine the clinical value of these biomarkers for risk stratification,” the researchers wrote.


  1. Thomson M et al. JAMA. 2013;309(22):2353-2361.