Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease
- Jeffrey T-J Huang1,2,3,
- Rekha Chaudhuri4,
- Osama Albarbarawi1,
- Alun Barton1,
- Christal Grierson1,
- Petra Rauchhaus1,
- Christopher J Weir5,
- Martina Messow6,
- Nicola Stevens3,
- Charles McSharry4,
- Giora Feuerstein2,
- Somnath Mukhopadhyay7,
- Jeffrey Brady1,2,3,
- Colin N A Palmer3,
- Douglas Miller2,
- Neil C Thomson4
- 1Translational Medicine Research Collaboration, Dundee, UK
- 2Clinical Research, Pfizer Worldwide Research & Development, Collegeville, Pennsylvania, USA
- 3Medical Research Institute, School of Medicine, University of Dundee, Dundee, UK
- 4Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, UK
- 5MRC Hub for Trials Methodology Research, University of Edinburgh, Edinburgh, UK
- 6Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
- 7Academic Department of Paediatrics, Brighton and Sussex Medical School, Brighton, UK
- Correspondence to Dr Jeffrey T-J Huang, Medical Research Institute, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK;
Contributors Conception and design: JH, RC, GF, SM, JB, CP, DM, NT; analysis and interpretation: JH, RC, AB, CG, OA, PR, CW, MM, CM, NS, DM, NT; drafting the manuscript for important intellectual content: JH, RC, NT.
- Received 1 April 2011
- Accepted 9 December 2011
- Published Online First 16 January 2012
Background Although an increased concentration of degraded elastin products in patients with chronic obstructive pulmonary disease (COPD) has been reported for many years, its clinical validity and utility remain uncertain due to technical difficulties, small study groups and the unknown relationship between exacerbation and elastin degradation. The objectives of this study were to determine the validity of urinary and blood total desmosine/isodesmosine in patients with COPD and asthma and to evaluate their relationship to exacerbation status and lung function.
Methods Urinary and blood desmosine levels were measured using validated isotopic dilution liquid chromatography–tandem mass spectrometry methods.
Results 390 study participants were recruited from the following groups: healthy volunteers, stable asthma, stable and ‘during an exacerbation’ COPD. Compared with healthy non-smokers, we found increased urinary or blood desmosine levels in patients with COPD, but no differences in patients with asthma or healthy smokers. The elevation of urinary desmosine levels was associated with the exacerbation status in patients with COPD. Approximately 40% of patients with stable and ‘during an exacerbation’ COPD showed elevated blood desmosine levels. Blood desmosine levels were strongly associated with age and were negatively correlated with lung diffusing capacity for carbon monoxide.
Conclusion The results suggest that urinary desmosine levels are raised by exacerbations of COPD whereas blood desmosine levels are elevated in a subgroup of patients with stable COPD and reduced lung diffusing capacity. The authors speculate that a raised blood desmosine level may identify patients with increased elastin degradation suitable for targeted therapy. Future prospective studies are required to investigate this hypothesis.
- COPD exacerbations
- lung physiology
- lung proteases
- asthma pharmacology
- COPD pharmacology
- respiratory infection
- COPD mechanisms
- COPD pathology
- asthma epidemiology
- asthma mechanisms
- allergic alveolitis
- allergic lung disease
- occupational lung disease
- tobacco and the lung
- asthma guidelines
Funding This work was funded by awards DU106 and GU90 from the Translational Medicine Research Collaboration – a consortium made up of the Universities of Glasgow, Edinburgh, Aberdeen and Dundee and the four associated NHS Health Boards (Greater Glasgow & Clyde, Lothian, Grampian and Tayside), Scottish Enterprise and Pfizer (formerly Wyeth) and supported financially by NHS Research Scotland, through the Scottish Primary Care Research Network.
Competing interests JH, GF, JB and DM were employed by Pfizer Inc. during the study. This does not alter their adherence to all the Thorax policies.
Patient consent Obtained.
Ethics approval Ethics approval was provided by ethics committees and Institutional Review Board (Glasgow and Dundee).
Provenance and peer review Not commissioned; externally peer reviewed.