Biomarkers of Chronic Airflow Limitation and COPD Identified by Mass Spectrometry

Abstract

RationaleChronic obstructive pulmonary disease (COPD) affects 300 million people worldwide and is the third leading cause of death according to WHO global health estimates. Early symptoms are subtle why COPD is often diagnosed at an advanced stage. Thus, there is an unmet need for biomarkers that can identify individuals at early stages of the disease before clinical symptoms have manifested. To date, few biomarkers are available for clinical diagnostic use in COPD.MethodsWe evaluated a panel of serum biomarkers related to inflammation and infection for their ability to discriminate between 77 subjects with chronic airflow limitation (CAL) and 142 subjects with COPD, respectively,versus150 healthy subjects (divided into two control groups that were matched with regards to age, gender and smoking to CAL and COPD). Healthy subjects and CAL were from Burden of Obstructive Lung Disease (BOLD), a population-based study. CAL was defined by post-bronchodilatory FEV1/FVC<0.7 in the BOLD population. COPD subjects were from Tools for Identifying Exacerbations (TIE), a COPD patient cohort. Quantification of 100 biomarker candidates was done by liquid chromatography-tandem mass spectrometry (LC-MS/MS).ResultsSeveral protein derived peptides were upregulated in CAL, compared to controls, most notably peptides representing histidine-rich glycoprotein (HRG), alpha-1-acid glycoprotein (AGP 1), alpha-1-antitrypsin (α1AT) and fibronectin. Out of these, HRG, AGP 1, and α1AT specific peptides were also elevated in the COPD cohort.ConclusionHRG, AGP 1 and α1AT biomarkers distinguish subjects with CAL and COPD from healthy controls. HRG and AGP 1 represent novel findings.