Changes In The Induced Sputum Proteome During Copd Exacerbations

Background: Improved knowledge of molecular mechanisms involved during acute exacerbations of COPD (AECOPD) is needed, in particular for different subsets of COPD. Aims: To perform quantitative proteomics analysis of induced sputum from stable and exacerbated COPD patients, and study proteome changes during exacerbations for COPD subgroups. Methods: We used paired induced sputum samples from 15 COPD patients (stable and exacerbation state). Proteins in the cell-free supernatant were digested into peptides, labeled with tandem mass tags, fractionated by mixed-mode chromatography and analyzed by liquid chromatography-tandem mass spectrometry. Results: More than 2000 proteins were identified in the sputum samples, and proteins were considered differently abundant between stable and exacerbated COPD or between different subgroups when p<0.05 and fold-change>1.5. Differences were found in exacerbated compared to stable COPD, including elevated levels of c-reactive protein, dickkopf-related protein-3, ferritin heavy chain, ficolin-1, perilipin-3, serine/arginine-rich splicing factor 1, and ubiquitin carboxyl-terminal hydrolase 15. Furthermore, differences in changes during AECOPD for patients with GOLD stage III/IV compared to II were demonstrated by clustering analysis (Figure 1). Conclusions: We found an altered sputum proteome during AECOPD, with differences in changes according to GOLD stage. These findings need to be validated in larger cohorts.