We established a sequential COPD-AE-RW rat model by cigarette-smoke and bacterial exposures in the first 8 weeks, and was challenged with Klebsiella pneumonia to mimic an AE on Day 1 of week 9, and found that body temperature, white blood cell, neutrophils, serum amyloid A (SAA) and C-reactive protein (CRP) increased in AECOPD rats 24 h after challenge, and declined in 3-6 d, while lung function declined in 48 h, and recovered in 7-16 d. When sacrificed, pulmonary forced expiratory volume (FEV)100 and FEV300 decreased, while elevated bronchoalveolar lavage fluid (BALF) neutrophils and marked airway inflammation, remodeling and emphysema were observed.
In COPDGene, the best combinations of biomarkers were: CC16, sRAGE, fibrinogen, CRP, and SP-D for airflow limitation (p < 10<sup>-4</sup>), SP-D, CRP, sRAGE and fibrinogen for emphysema (p < 10<sup>-3</sup>), CC16, fibrinogen, and sRAGE for decline in FEV<sub>1</sub> (p < 0.05) and progression of emphysema (p < 10<sup>-3</sup>), and all five biomarkers together for mortality (p < 0.05).