Sara Ongay1, Marijke Sikma1,2, Peter Horvatovich2, Jos Hermans1, Bruce E Miller3, Nick H T Ten Hacken4, Rainer Bischoff1. 1. University of Groningen, Department of Pharmacy, Analytical Biochemistry, Groningen, The Netherlands. 2. Van Hall Larenstein Hogeschool, Leeuwarden, Agora, The Netherlands. 3. GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania. 4. University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Abstract
Background: Desmosine (DES) and isodesmosine (IDES) have been widely discussed as potential biomarkers of COPD. However, their clinical utility and validity remains unproven. Aim: This study aims to progress DES/IDES evaluation as a chronic obstructive pulmonary disease (COPD) biomarker by investigating its urinary excretion in a large sample cohort with respect to a) which factors influence DES/IDES levels in a population of healthy control individuals and COPD individuals; b) whether DES/IDES levels enable the differentiation between COPD individuals and healthy control individuals; c) whether DES/IDES can be used to differentiate between fast and slow decliners in lung function. Methods: Urinary DES and IDES were quantified in 365 individuals (147 healthy control individuals and 218 COPD individuals) from the Evaluation of COPD Longitudinally to Indentify Predictive Surrogate Endpoints (ECLIPSE) study (NCT00292552) by employing a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Results: Age, gender, body mass index (BMI) and smoking have a significant (p<0.05) influence on DES/IDES urinary excretion and need to be corrected for when investigating DES/IDES as a disease biomarker. Urinary DES/IDES allowed a statistically relevant differentiation (p<0.05) between stable COPD individuals and healthy control individuals, however, assay sensitivity and specificity were low (62% and 73%, respectively). Furthermore, urinary DES/IDES does not allow the differentiation of fast and slow decliners in lung function. Conclusions: The present results suggest that while urinary DES/IDES excretion is related to COPD, it is not a sensitive or specific biomarker for COPD diagnosis or prognosis.
Background: Desmosine (DES) and isodesmosine (IDES) have been widely discussed as potential biomarkers of COPD. However, their clinical utility and validity remains unproven. Aim: This study aims to progress DES/IDES evaluation as a chronic obstructive pulmonary disease (COPD) biomarker by investigating its urinary excretion in a large sample cohort with respect to a) which factors influence DES/IDES levels in a population of healthy control individuals and COPD individuals; b) whether DES/IDES levels enable the differentiation between COPD individuals and healthy control individuals; c) whether DES/IDES can be used to differentiate between fast and slow decliners in lung function. Methods: Urinary DES and IDES were quantified in 365 individuals (147 healthy control individuals and 218 COPD individuals) from the Evaluation of COPD Longitudinally to Indentify Predictive Surrogate Endpoints (ECLIPSE) study (NCT00292552) by employing a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Results: Age, gender, body mass index (BMI) and smoking have a significant (p<0.05) influence on DES/IDES urinary excretion and need to be corrected for when investigating DES/IDES as a disease biomarker. Urinary DES/IDES allowed a statistically relevant differentiation (p<0.05) between stable COPD individuals and healthy control individuals, however, assay sensitivity and specificity were low (62% and 73%, respectively). Furthermore, urinary DES/IDES does not allow the differentiation of fast and slow decliners in lung function. Conclusions: The present results suggest that while urinary DES/IDES excretion is related to COPD, it is not a sensitive or specific biomarker for COPD diagnosis or prognosis.
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