Proteinase-3 in plasma and BAL in patients with COPD

<bold>Background:</bold> The serine proteases proteinase-3 (PR3) and neutrophil elastase (NE) are potential factors in COPD pathogenesis, with the role of PR3 less described. We examined the levels of PR3 and NE in plasma and bronchoalveolar lavage (BAL) in patients with COPD compared to controls. <bold>Methods:</bold> 130 patients with COPD and 103 controls, aged 36-83 years, participated in the Bergen COPD Microbiome Study from 2012-2015. A structured interview was performed and blood samples were drawn prior to bronchoscopy with BAL. PR3 and NE were measured in plasma and BAL with enzyme immunoassays. PR3 and NE were log transformed and multivariable linear regression analyses were used to examine associations with sex, age, smoking, body composition and white cell counts for all, and exacerbation history, GOLD stage and inhaled steroid use in COPD. <bold>Results:</bold> PR3 levels in plasma were higher in COPD patients than controls; median (IQR) 368 (291-471) vs. 332 (250-417) ng/ml, respectively, p <0.01. NE levels in plasma did not differ between groups. In BAL, levels of both PR3 (median 52 (29-122) vs. 36 (23-75) ng/ml) and NE (median 128 (53-198) vs. 72 (29-161) ng/ml) were higher in COPD patients than controls, p=0.01. PR3 was strongly associated with neutrophils in both plasma and BAL (p<0.01). PR3 in plasma increased with age >70 years and obesity, with geometric mean (GM) ratios of 1.23 (1.01-1.49) and 1.22 (1.01-1.48) respectively, after adjustment. Daily smoking suppressed PR3 in BAL of COPD patients; GM ratio 0.24 (0.12-0.51) after adjustment. <bold>Conclusion:</bold> COPD patients had higher levels of PR3 in both plasma and BAL, but were not significantly associated with exacerbation history, GOLD stage or inhaled steroid use.