Alterations in sputum inflammatory markers during exacerbations for COPD patients with different stable state levels

Background: Although several inflammatory markers are increased in sputum of COPD patients, inflammatory responses during exacerbations for different subsets of COPD patients are less studied. Aims: To investigate changes in sputum inflammatory markers IL-6, IL-8, IL-18, IP-10 (CXCL10), MIG (CXCL9) and TNF-α between stable state and exacerbations for COPD patients with different stable state levels of the same markers. Methods: Paired induced sputum samples were collected from 39 COPD patients (stable and exacerbation state) in the Bergen COPD Cohort and Bergen COPD Exacerbation Studies. Inflammatory markers were analyzed by a bead-based immunoassay. Wilcoxon rank sum test, Wilcoxon signed rank test and Spearman’s rank correlation were used for statistical analyses. Results: There was a significant negative correlation between sputum stable state levels and changes during COPD exacerbations for most of the markers (changes are defined as exacerbation minus stable state levels). Spearman’s rho (with CI) for IL-6 was -0.72(-0.85, -0.51),p<0.001, for IL-8 -0.61(-0.78, -0.35),p<0.001, for IL-18 -0.35(-0.60, -0.03),p=0.030, for IP-10 -0.31(-0.58, 0.02),p=0.055, for MIG -0.38(-0.93, -0.07),p=0.016, and for TNF-α -0.44(-0.67, -0.13),p=0.006. Some markers showed significantly higher levels in GOLD stage III/IV compared to GOLD stage II patients in stable state sputum samples, but decreased upregulation (change) during exacerbations for GOLD stage III/IV compared to GOLD stage II. Conclusions: Our results suggest that COPD patients with high levels of sputum inflammatory markers in the stable state have less potential for upregulation of the markers during exacerbations.