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

Rationale: Proteomics may identify a useful panel of biomarkers for identification of asthma and chronic obstructive pulmonary disease (COPD). Objectives: To conduct an unsupervised analysis of peripheral blood proteins in well-characterized subjects with asthma and COPD, and identify and validate a biomarker panel for disease discrimination. Methods: Two-dimensional difference gel electrophoresis was used to separate plasm a proteins from healthy control subjects, stable patients with asthma, and individuals with COPD. Candidate protein markers were identified by matrix assisted laser desorption ionization time of flight mass spectrometry and subsequently validated in two populations via immunoassay. A panel of four biomarkers was selected and their ability to distinguish between groups was assessed in isolation and in combination in two separate validation populations. Measurements and Main Results: Seventy-two protein spots displayed significantly different expression levels between the three subject groupings (P < 0.05). Fifty-eight were positively identified, representing 20 unique proteins. A panel of four biomarkers (alpha(2)-macroglobulin, haptoglobin, ceruloplasmin, and hemopexin) was able to discriminate with statistical significance between the clinical groups of patients with asthma, patients with COPD, and control subjects, and these results were confirmed in a second clinical population of older adults with airflow obstruction. Conclusions: Proteomics has identified novel biomarkers for asthma and COPD, and shown that the iron metabolism pathways and acute-phase response may be involved in the pathogenesis of airway disease. The panel of peripheral blood biomarkers has the potential to become an extremely useful addition to the clinical diagnosis and management of respiratory disease.