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Mortality associated with biomarkers of collagen remodeling in COPD

New research links high levels of serological biomarkers of collagen remodeling with increased mortality in patients with chronic obstructive pulmonary disease, revealing assessment of tissue turnover in the parenchyma and small airways can help the prognosis of COPD, according to a recent study published in Respiratory Research.

“The chronic inflammatory process in the lungs of individuals with COPD induces the remodeling of the extracellular matrix (ECM), which includes both degradation of old proteins and synthesis of new ones and occurs in both small airways and alveolar walls,” Jannie M. B. Sand, PhD, MSc, from Nordic Bioscience and the department of public health at the University of Copenhagen, and colleagues report. “As excessive ECM remodeling resulting from repetitive injury is associated with COPD, we hypothesized that measuring serological biomarkers of ECM protein remodeling would be helpful in predicting all-cause mortality in individuals with COPD.”

To identify COPD patients at risk for disease progression and mortality, the researchers investigated biomarkers of ECM degradation and formation in a subpopulation (n = 1,000) of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) cohort.

The investigators validated immunoassays measuring serological neo-epitopes produced by proteolytic cleavage associated with degradation of collagen type I, II, IV, and VI, elastin, and biglycan, and formation of collagen type VI. They also included analyses of the previously studied CRP (C-reactive protein) and fibrinogen, then used multivariate models to assess the prognostic value of these biomarkers.

During follow-up, thirty subjects died (3%). Sand and associates found nonsurvivors were older, had reduced exercise capacity, increased dyspnea score, and included fewer current smokers. In comparison to survivors, the researchers observed significantly elevated collagen biomarkers in non-survivors (including C1M, C3A, C3M, C4M, C6M, ProC6, ELM7, and CRPM). Subjects with collagen remodeling biomarkers in the upper quartile saw increased mortality risk, notably for the degradation fragment of collagen type IV C6M (hazard ratio 6.6; 95% CI, 2.9-15.2; P < .0001) after adjusting for relevant cofounders.

“These biomarkers were prognostic for all-cause mortality, suggesting that a high remodeling rate is related to increased risk of mortality,” Sand and colleagues conclude. “The increased degradation of collagens found in the interstitial matrix of the lungs, indicate that ECM turnover is important in the pathology of COPD.”– by Savannah Demko

Disclosure: The researchers report no relevant financial disclosures.