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02-07-2013 | Respiratory | Article

Biomarker offers new understanding of COPD–asthma overlap


Free abstract

medwireNews: Researchers have identified a sputum biomarker that could distinguish patients with chronic obstructive pulmonary disease (COPD)-asthma overlap syndrome from those with COPD alone.

Witold Mazur (University of Helsinki, Finland) and colleagues found that neutrophil gelatinase-associated lipocalin (NGAL) was significantly increased in the sputum of patients with overlap syndrome compared with patients with COPD.

"Elevated levels of NGAL might be a characteristic feature of overlap that could differentiate overlap from COPD, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD-asthma overlap," they suggest.

The study, published in the European Respiratory Journal, included 18 nonsmokers, 17 healthy smokers, 25 asthma patients, 28 COPD patients, and 11 COPD-asthma overlap patients who were tested for four biomarkers previously associated with COPD.

Of the four biomarkers studied, three showed consistent patterns in both COPD and overlap syndrome compared with asthma: plasma sRAGE (soluble receptor for advanced glycation end-products) was significantly decreased; plasma SP-A (surfactant protein A) was significantly elevated; and sputum MPO (myeloperoxidase) levels were significantly elevated.

However, sputum levels of the fourth biomarker NGAL were significantly greater in patients with overlap syndrome than in patients with COPD alone, in whom levels were not significantly greater than in patients with asthma.

And, area under the receiver operating characteristic curve analysis showed that NGAL was the only biomarker that could distinguish patients with overlap from those with COPD, with a sensitivity of 73% and a specificity of 71% at a cutoff of 4.4 µg/mL. All of the biomarkers could also significantly distinguish overlap and COPD from asthma alone and nonsmoking controls.

Mazur and colleagues also note that sputum MPO levels in their study independently correlated with levels of sputum neutrophils, suggesting that neutrophil-driven inflammation is common to both COPD and overlap. However, NGAL levels significantly correlated with airflow obstruction independently of neutrophil levels, which they say could be due to NGAL secretion by respiratory epithelial cells themselves in response to airway inflammation.

"Taken together, these results… suggest that while airway neutrophilic inflammation and peripheral lung destruction are common pathological processes in overlap and COPD, COPD-asthma overlap is associated with enhanced airway inflammation, which can be detected by increased levels of sputum NGAL," the team writes.

"These findings might have implications for the distinct clinical characteristics of COPD-asthma overlap, but further investigation will be needed to clarify the mechanisms of airway inflammation and the optimal monitoring and treatment strategy of overlap patients."

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Kirsty Oswald, medwireNews Reporter

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