Inflammatory Biomarkers Predict Chronic Pulmonary Disease Outcome

Changes in inflammatory biomarkers establish clinical variables and improve the prediction of mortality in patients with chronic obstructive pulmonary disease (COPD).

COPD is characterized by low-grade systemic inflammation and the addition of inflammatory biomarker blood tests would establish predictive factors that will improve accuracy of a prognostic model for mortality.

An international multicenter team of scientists led by those at Brigham and Women’s Hospital (Boston, MA, USA) prospectively collected data on 1,843 COPD patients from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Of these 1,843 patients, 168 (9.1%) died during the three-year follow-up.

The biomarkers measured from serum samples were: Chemokine (C-C motif) ligand 18 (CCL-18 or pulmonary and activation-regulated chemokine, PARC), surfactant protein D (SP-D), interleukin 8 (IL-8), Clara cell secretory protein 16 (CC-16), and tumor necrosis factor alpha (TNFα). Fibrinogen and C-reactive protein (CRP using a high sensitivity method) were measured in plasma samples. All protein biomarkers were measured by validated immunoassays. Total white blood cells (WBC) and neutrophils were counted by an automated method.

The results of the study show that a panel of selected biomarkers, WBC counts, IL-6, fibrinogen, CCL-18, CRP, IL-8, and SP-D were not only elevated in nonsurvivors compared with survivors, but were also associated with mortality over three years after adjusting for clinical variables known to predict death in COPD. Bartolome M. Celli, MD, the lead author of the study, 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 to clinical predictors in COPD patients adds relevant prognostic information." The study was published on March 23, 2012, in the American Journal of Respiratory and Critical Care Medicine.

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