A study recently published in the journal Respiratory Research proposes new potential biomarkers for chronic obstructive pulmonary disease (COPD) activity in patients. The study is entitled “Accelerated extracellular matrix turnover during exacerbations of COPD” and was conducted by researchers at Nordic Bioscience, the University of Copenhagen and the Hvidovre Hospital in Denmark and the University of Nottingham in the United Kingdom.

COPD is one of the most common lung diseases and a major cause of morbidity and mortality worldwide, being the third leading cause of death in the United States. It is a progressive disease in which individuals develop serious problems in breathing with obstruction of the airways, shortness of breath (dyspnea), cough and acute exacerbations. Smoking is considered to be the leading cause of COPD. The disease can seriously impact the patient’s physical capacity, well-being and social functioning. Biomarkers are urgently needed to assess COPD activity and progression in patients.

Exacerbations in COPD patients represent periods of increased disease activity, and these significantly contribute to disease progression and accelerate the loss of lung function. Exacerbations usually become more frequent as the disease severity increases. The structural changes that occur in the lung tissue during exacerbations are, however, poorly elucidated. The extracellular matrix (ECM) of the lungs (composed by collagen, elastin and proteoglycans) is constantly renewed (turnover) as part of the natural process to maintain a healthy tissue. However, excessive ECM turnover has been suggested to be linked to COPD and promote lung function loss.

In the study, researchers hypothesized that the turnover of ECM proteins might be accelerated during COPD exacerbations, and that it could possibly serve as a biomarker of disease activity and prognosis. The team analyzed ECM turnover in 69 COPD patients who had been hospitalized due to an exacerbation and at a 4 week follow-up visit. ECM turnover was assessed by analyzing different markers of protein degradation and formation, namely collagen types III (Pro-C3 and C3M), IV (P4NP 7S and C4M) and VI (Pro-C6 and C6M), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM).

Researchers found high circulating levels of protein degradation fragments (C3M, C4M, C6M, ELM7 and EL-NE) during the COPD exacerbation in comparison to the follow-up visit. VCANM and pro-C6 levels were found to be decreased during the exacerbation, while pro-C3 levels were unchanged. In general, degradation/formation ratios were found to be increased for collagen types III and VI and decreased for collagen type IV during an exacerbation.

The team concluded that COPD exacerbations are linked to an accelerated ECM turnover in the lungs, being accompanied by a rise in the levels of circulating fragments of ECM structural proteins. The team suggests that these ECM protein fragments could be used as biomarkers of disease activity.