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doi:10.1378/chest.06-2251
(Chest. 2007; 131:1363-1371)
© 2007 American College of Chest Physicians
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Measurements of Desmosine and Isodesmosine by Mass Spectrometry in COPD*

Shuren Ma, PhD; Yong Y. Lin, PhD and Gerard M. Turino, MD

* From the James P. Mara Center for Lung Disease, Department of Medicine, St. Luke’s-Roosevelt Hospital Center, Columbia University College of Physicians & Surgeons, New York, NY.

Correspondence to: Gerard M. Turino, MD, St. Luke’s-Roosevelt Hospital, Department of Medicine, 1000 Tenth Ave, Mara Center, 3rd Floor, New York, NY 10019; e-mail: gmt1{at}columbia.edu

Abstract

Objectives: Application of mass spectrometry (MS) for direct measurements of desmosine (D) and isodesmosine (I) in urine, plasma, and sputum as markers of elastin degradation in patients with {alpha}1-antitrypsin deficiency (AATD) and non-AATD-related COPD.

Background: In COPD patients, the lungs undergo elastin injury, which can be monitored by measurements of D and I in body fluids as specific markers of elastin degradation using the specificity and sensitivity of MS.

Methods: Acid hydrolysis of blood plasma, 24-h urine and sputum measurements, followed by chromatographic separation for mass spectrometric analysis.

Results: Each patient group had levels of plasma D and I that were statistically significantly higher than those of control subjects. AATD patients had higher levels than COPD patients with normal {alpha}1-antitrypsin (AAT) levels. Twenty-four-hour urine measurements demonstrated no significant difference in total levels of D and I among control subjects and patients but showed a free (unbound) concentration of D and I in urine, which was statistically significantly higher in patients with COPD with and without AAT. The D and I levels in the sputum of patients with AATD exceeded the levels in COPD patients with normal AAT levels.

Conclusions: MS allows a sensitive and specific analysis of D and I in body fluids. The quantification of D and I in sputum, along with increases of D and I in plasma and an elevated free component of D and I in urine provide indexes that characterize patients with COPD and can be followed in relation to the course of the disease and/or therapy.

Key Words: {alpha}1-antitrypsin deficiency • COPD • desmosine • elastin • emphysema • isodesmosine • liquid chromatography • mass spectrometry







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