According to a study published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine, adding inflammatory biomarkers to established clinical variables significantly improves the prediction of mortality in patients suffering with chronic obstructive pulmonary disease (COPD).

Lead author Bartolome Celli, lecturer in medicine at Harvard Medical School and member of the Pulmonary and Critical Care Division of Brigham and Women’s Hospital in Boston, said:

“COPD is characterized by low-grade inflammation, so we hypothesized that the addition of inflammatory biomarkers to established predictive factors would improve the prediction of mortality. We found that the addition of a panel of selected biomarkers to clinical variable significantly improved the ability of clinical variables to predict mortality in these patients.”

The team examined data on 1,843 individuals with COPD from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. During the three-year follow-up, the researchers found that 168 (9.1%) of the 1,843 participants died.

Clinical predictors of mortality included:

  • Number of hospitalizations caused by COPD exacerbations in the year before the study
  • Age
  • BODE (Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity) index

A predictive model for mortality using these clinical variables had a C-statistic of 0.686. C-statistic measures the ability of how effectively a clinical prediction rule can accurately rank-order patients by risk.

The researchers found that the C-statistic considerably improved to 0.708 by adding interleukin-6 (IL-6) to the predictive model. In addition, adding a group of biomarkers, including IL-6, white blood cell counts, fibrinogen, chemokine (C-C-motif) ligand 18 (CCL-18), C-reactive protein (CRP), surfactant protein D (SP-D), and interleukin-8 (IL-8) improved the C-statistic to 0.726.

Dr. Celli, explained:

“This panel of selected biomarkers was not only elevated in non-survivors in our cohort, but was associated with mortality over three years of follow-up after adjusting for clinical variables known to predict mortality in patients with COPD.

Except for IL-6, these biomarkers improved the predictive value of our model only marginally when considered individually, but they improved the model significantly when analyzes as a group.”

Limitations of the study included:

  • No study adjudication committee to specify causes of death
  • No validating cohort
  • and the exclusion of some biomarkers considered to be vital in the pathobiology of COPD

Dr. Celli, said:

“Adding white blood cell counts and measurement of changes in systemic levels of IL-6, CRP, IL-8, fibrinogen, CCL-18, and SP-D significantly improves the ability of clinical variables to predict mortality in patients with COPD. This is the first study to show that the addition of biomarker levels of clinical predictors in COPD patients adds relevant prognostic information.”

Written by Grace Rattue