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Biomarker Combinations Successfully Discriminate Between Asthma and COPD

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Researchers in Australia have identified a panel of four biomarkers that may aid in the diagnosis and management of asthma and chronic obstructive pulmonary disease (COPD). The study, published in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine, found that the biomarkers may be used in different combinations to successfully identify patients with either of the airway diseases.

Blood samples were collected from 43 patients (average age = 48) divided into three clinical groups: 21 patients with asthma, 5 patients with COPD and 17 healthy control individuals. Using 2-dimensional difference gel electrophoresis, the researchers identified 20 unique plasma proteins as potential candidate biomarkers. The proteins fell into 3 general functional groups: iron metabolism, the coagulation cascade, and complement pathways.

Serum concentrations of three proteins – ceruloplasmin (CP), haptoglobin (HP) and antithrombin III (SERPINC1 or AT3) – were higher in asthmatic patients than in healthy controls. Patients with COPD had serum levels of prothrombin (F2) that were lower than levels observed in either asthmatic patients or healthy controls. These results were then validated in 7 additional patients with asthma and 9 with COPD.

A similar validation study was conducted on a group of 73 older adults (age >55 years): 14 patients with asthma, 22 patients with COPD, 14 patients with both asthma and COPD, and 23 age-matched, healthy control individuals. Ceruloplasmin and haptoglobin were again found to be higher in asthmatic patients that in healthy controls. Serum levels of another protein, hemopexin (HPX), was also found to be elevated.

Haptoglobin and hemopexin were also higher in patients with overlapping asthma and COPD compared to control patients. Although there were no significant protein elevations in patients with COPD, there was a trend toward higher levels of ceruloplasmin, haptoglobin, hemopexin and alpha 2 macroglobulin (A2M).

Taken together, these findings suggest that four proteins – ceruloplasmin, haptoglobin, hemopexin and alpha 2 macroglobulin – can be used in combination to identify patients with asthma and COPD. For example, in the younger patients, the combination of ceruloplasmin and haptoglobin was best at discriminating between children with asthma and healthy control patients; in older patients, haptoglobin and hemopexin were more effective. The proteins identified are predominantly liver-synthesized proteins that can have anti-inflammatory activity through the inhibition of oxidative stress. Additionally, they are also involved in iron sequestration, which has an antimicrobial effect.

Peter G. Gibson, MD, conjoint professor at the University of Newcastle’s School of Medicine and Public Health, said:

Using a proteomics approach, we have identified a panel of four blood-based biomarkers that, when used in combination, can discriminate between healthy controls, asthmatics and individuals with COPD, and has the potential to be a valuable tool in the clinical diagnosis of respiratory disease. The proteins in the diagnostic biomarker panel are all involved in the regulation of inflammation, and usually function as anti-inflammatory proteins.

Study: Identification of Novel Diagnostic Biomarkers for Asthma and Chronic Obstructive Pulmonary Disease

Source: American Thoracic Society