Clinical validity of blood and urinary desmosine as biomarkers for chronic obstructive pulmonary disease

Background: Although the elevation of degraded elastin products in patients with COPD has been reported for many years, its clinical validity and utility remain uncertain due to technical difficulties, small study cohorts and unknown relationship between exacerbation and elastin degradation. Aims and objectives: To determine the validity of urinary and blood total desmosine/isodesmosine (uDES and bDES) as disease phenotyping biomarkers for COPD and to evaluate their relationship to exacerbation status. Methods: uDES and bDES were measured using validated isotopic dilution LC-MS/MS methods. Results: Two cohorts consisting of a total of 390 subjects including the following groups: healthy volunteers, stable asthma, stable COPD and COPD during an exacerbation were investigated. Compared to healthy non-smokers, we found increased bDES levels in patients with COPD regardless of exacerbation status (p<0.001, ANOVA), but no differences in patients with asthma or healthy smokers. A similar observation was found for uDES except that the elevation of uDES levels was associated with an exacerbation in COPD patients (12±5 vs. 20±12 ng/mg creatinine for stable and exacerbation, respectively, p<0.01, t test). Such an increase in COPD patients during an exacerbation was closely related to inflammation associated proteinuria (p<0.001, Spearman correlation). Approximately 40% of patients showed an “accelerated elastin degradation” phenotype based on their bDES levels in both stable COPD and COPD during an exacerbation. Conclusions: Our results strongly suggest that bDES is a valid biomarker for phenotyping “accelerated elastin degradation” subtype in COPD whilst uDES links to exacerbation.