Serum Amyloid A Is a Biomarker of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Abstract

Much of the total disease burden and cost of chronic obstructive pulmonary disease (COPD) is associated with acute exacerbations of COPD (AECOPD). Serum amyloid A (SAA) is a novel candidate exacerbation biomarker identified by proteomic screening. To assess SAA as a biomarker of AECOPD. Biomarkers were assessed (1) cross-sectionally (stable vs. AECOPD; 62 individuals) and (2) longitudinally with repeated measures (baseline vs. AECOPD vs. convalescence; 78 episodes in 37 individuals). Event severity was graded (I, ambulatory; II, hospitalized; III, respiratory failure) based on consensus guidelines. Presumptively newly acquired pathogens were associated with onset of symptomatic AECOPD. In the cross-sectional study, both SAA and C-reactive protein (CRP) were elevated at AECOPD onset compared with stable disease (SAA median, 7.7 vs. 57.6 mg/L; P < 0.01; CRP median, 4.6 vs. 12.5 mg/L; P < 0.01). Receiver operator characteristics analysis was used to generate area-under-curve values for event severity. SAA discriminated level II/III events (SAA, 0.88; 95% confidence interval, 0.80-0.94 vs. CRP, 0.80; 95% confidence interval, 0.70-0.87; P = 0.05). Combining SAA or CRP with major symptoms (Anthonisen criteria, dyspnea) did not further improve the prediction model for severe episodes. IL-6 and procalcitonin were not informative. SAA is a novel blood biomarker of AECOPD that is more sensitive than CRP alone or in combination with dyspnea. SAA may offer new insights into the pathogenesis of AECOPD.