desmosine and Acute-Disease

Desmosine (DES) is an elastin-derived, cross-link amino acid, which is not metabolized; hence, its urinary levels reflect elastin breakdown. We hypothesized that elastin degradation should increase as a result of increased lung inflammation during an acute exacerbation of COPD and should decrease after recovery. To test this hypothesis we measured DES in three urine samples from nine COPD subjects during the first 5 days of an acute exacerbation and at 2 months after recovery. We also measured forced expiratory volume in 1 sec (FEV1) to monitor the effects ofthe exacerbation on ventilatory function. The mean (SD) FEV1 was 45 (15)% predicted during the exacerbation and 57.8 (16)% predicted 2 months later (P=0.00001). The mean (SD) DES excretion was 25.3 (9) microg g(-1) creatinine at day 1;23.5 (9) at day 3 and 24 (9) at day 5 of the exacerbation. The mean (SD) urinary DES excretion 60 days after discharge was 20.9 (7) microg g(-1) creatinine (P=0.049) in comparison with the mean of the three acute-phase values. The size of the increase in desmosine excretion during exacerbation is small, 3.2 microg g(-1) creatinine or 16% of the recovery desmosine value. We conclude that there is a small but statistically significant increase in lung elastin breakdown in the body during an acute exacerbation of COPD.

Topics: Acute Disease; Aged; Analysis of Variance; Biomarkers; Chromatography, Micellar Electrokinetic Capillary; Desmosine; Elastin; Forced Expiratory Volume; Humans; Longitudinal Studies; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive

We evaluated the ability of intravenous supplementation therapy with alpha(1)-antitrypsin (AAT) to reduce the rate of urinary excretion of desmosine (DES), a specific marker of elastin degradation, in eight men and four women with emphysema due to severe, congenital deficiency of AAT (range 17-69 mg/dl). Nine were former cigarette smokers, two were current smokers, and one reported never smoking; their mean age was 54 (SD 12) yr and their mean FEV(1) was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion was 13.0 (5.0) microg/g creatinine, 73% higher than in healthy nonsmokers. During 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (5.9) microg/g creatinine, unchanged from the baseline period (p = 0.85 by repeated measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high and that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time.

Topics: Acute Disease; Adult; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Analysis of Variance; Cotinine; Desmosine; Elastin; Female; Humans; Infusions, Intravenous; Lung; Male; Pulmonary Emphysema; Time Factors

A modified radioimmunoassay (RIA) for desmosine in the urine was investigated as a tool for the rapid estimation of lung elastin catabolism. Cystic fibrosis (CF) and oxygen toxicity were chosen as conditions that might show altered elastin destruction. Using an antibody bound to magnetic particles the RIA was adapted to handle large numbers of samples requiring only 50 microliters or urine. The experiments show that it was not necessary to hydrolyze or extract the urine prior to assay and that collecting spot urines and normalizing the data to urine creatinine gives the same interpretation of the data as total desmosine in a 24-hour collection. Urine desmosine levels were elevated in 10 of 16 patients with CF; however, daily fluctuations were considerable in some subjects, varying as much as 5-fold and underlining the importance of assaying several consecutive days of urine in acute disorders for an accurate estimate of desmosine excretion. The RIA for desmosine is a rapid and sensitive assay that requires no sample preparation and could be applied to clinical situations that require large numbers of samples.

Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Cystic Fibrosis; Desmosine; Humans; Hyperoxia; Male; Radioimmunoassay; Sensitivity and Specificity