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Pediatric Pulmonology Sep 2012Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and...
RATIONALE
Cystic fibrosis (CF) lung disease is characterized by structural changes and remodeling in airway architecture and lung parenchyma. Neutrophilic inflammation and infection lead to injury and breakdown of airway matrix constituents, including elastin. The non-invasive measurement of urinary desmosine (UDes), a breakdown product of elastin, may be reflective of ongoing lung injury and may serve as a biomarker of active short-term damage during pulmonary exacerbation. Our objectives were to measure desmosine in the urine of CF patients hospitalized for treatment of a pulmonary exacerbation and to explore the correlation between desmosine concentration and other markers of clinical improvement, including lung function and inflammatory mediators.
METHODS
Urine and blood samples plus lung function measurements were collected at up to three points during hospitalization for treatment of a CF pulmonary exacerbation. We used a repeated measures model, adjusted for age and time between measurements, to compare log transformed urine desmosine concentrations across multiple time points and to correlate those concentrations with related clinical variables. Change in UDes concentration was investigated using a statistical model that incorporated normalization factors to account for variations in urinary concentration.
RESULTS
Desmosine was measured by radioimmunoassay (RIA) in 155 spot urine samples from 53 CF patients hospitalized for 63 pulmonary exacerbations (range of results: 0-235 pmol Des/ml). Specific gravity (SG) adjusted UDes concentration decreased significantly during admission for CF pulmonary exacerbation, P < 0.01 (average length of stay = 11 days). No correlation was observed between UDes concentration and lung function or inflammatory markers.
CONCLUSIONS
UDes decreased significantly following treatment for an acute pulmonary exacerbation and may be a useful biomarker of short-term injury to the CF lung. Further investigation is needed to evaluate the utility of UDes concentration in the long-term progression of CF lung disease.
Topics: Airway Remodeling; Biomarkers; C-Reactive Protein; Cohort Studies; Cystic Fibrosis; Desmosine; Disease Progression; Elastin; Female; Humans; Interleukin-8; Lung Injury; Male; Pneumonia; Prospective Studies; Respiratory Function Tests
PubMed: 22431382
DOI: 10.1002/ppul.22525 -
Biomarkers : Biochemical Indicators of... 2006Acute lung injury (ALI) is a complex disorder associated with an acute inflammatory response thought to contribute to tissue injury. Desmosine, a cross-linking amino...
Acute lung injury (ALI) is a complex disorder associated with an acute inflammatory response thought to contribute to tissue injury. Desmosine, a cross-linking amino acid present in elastin, is released during matrix degradation and cleared by the kidney. Results from animal models and human disease studies have suggested that ALI is associated with the release of desmosine, resulting in increased urinary desmosine. A radioimmunoassay was used to monitor urinary desmosine levels over 10 days in ten patients with ALI. The concentration of desmosine was measured with and without acid hydrolysis. Baseline urinary desmosine was increased in two of ten patients. The concentration of desmosine at baseline did not appear to be related to age, gender, neutrophil elastase (NE)/alpha(1)-antiprotease complex concentration or P(a)O(2)/F(i)O(2) ratio. No meaningful changes in desmosine levels were noted after removal from mechanical ventilation. Baseline desmosine concentrations did not appear to correlate with the risk of death. The limited sensitivity, predictive correlations and dynamic modulation would suggest that urine desmosine has a limited role as a biomarker for ALI. Hydrolysis of urine samples appears necessary for optimal measurement of urine desmosine.
Topics: Aged; Aged, 80 and over; Biomarkers; Desmosine; Female; Humans; Male; Middle Aged; Radioimmunoassay; Reference Standards; Reproducibility of Results
PubMed: 16484139
DOI: 10.1080/13547500500343225 -
ERJ Open Research Oct 2018http://ow.ly/vN6N30mhBA1.
http://ow.ly/vN6N30mhBA1.
PubMed: 30443554
DOI: 10.1183/23120541.00136-2018 -
Analytical Biochemistry May 2013Elastin is one of the major extracellular matrix proteins associated with connective tissue. Its degradation leads to the liberation of the unique amino acids desmosine... (Randomized Controlled Trial)
Randomized Controlled Trial
Elastin is one of the major extracellular matrix proteins associated with connective tissue. Its degradation leads to the liberation of the unique amino acids desmosine and isodesmosine. These have shown utility as biomarkers of elastin breakdown for disease progression, patient stratification, and drug efficacy. So far, the quantitation of desmosines in plasma is hampered by complex sample preparation. Here we demonstrate an improved and simplified procedure for detecting both free and total desmosines. The method is based on spiking with a deuterium-labeled desmosine standard, ethanol precipitation, propionylation, high-performance liquid chromatography (HPLC) separation, and selected reaction monitoring (SRM) mass spectrometry. The performance of the assay is illustrated by comparing the levels of free and total desmosines in normal healthy plasma and those from patients diagnosed with chronic obstructive pulmonary disease (COPD). A conserved ratio of 1:3 for free to total desmosine was found. The determination of free desmosine has higher accuracy than that of total desmosine; therefore, it is the method of choice when plasma volume is limiting. Finally, we show that the plasma desmosine concentration correlates with age and body mass index.
Topics: Adult; Age Factors; Aged; Biomarkers; Body Mass Index; Body Weight; Case-Control Studies; Chemical Precipitation; Chromatography, High Pressure Liquid; Desmosine; Deuterium; Female; Humans; Isodesmosine; Male; Mass Spectrometry; Middle Aged; Pulmonary Disease, Chronic Obstructive; Reference Values; Reproducibility of Results; Russia; Smoking; United States
PubMed: 23399390
DOI: 10.1016/j.ab.2013.01.012 -
Experimental Lung Research Sep 1989Measurement of urinary desmosine in experimental models of emphysema has been used to demonstrate elastin catabolism. In order to evaluate the hypothesis that... (Comparative Study)
Comparative Study
Measurement of urinary desmosine in experimental models of emphysema has been used to demonstrate elastin catabolism. In order to evaluate the hypothesis that accelerated elastin degradation also occurs in association with acute lung injury characterized by fibrotic repair, we prepared acid hydrolysates of lung lavage (LL) and used a radioimmunoassay for desmosine to measure concentrations of this elastic-specific cross-link in LL. Lavage desmosine (pmol/100 microliter LL) was measured following bleomycin-induced lung injury in marmosets and was shown to be elevated at 1 week (median 6.0, range 5.1-7.8), 2 weeks (8.4, 6.2-8.7), and 4 weeks (7.6, 4.8-7.8) compared to control levels (1.8, 1.4-3.7). Elevations of lavage desmosine after bleomycin were temporarily associated with remodeling of the lung as indicated by increased total lung collagen, reduced diffusing capacity and lung compliance, and histologic evidence of pulmonary fibrosis. Bronchoalveolar lavage (BAL) desmosine was measured in patients with the Adult Respiratory Distress Syndrome (ARDS) and compared with patients at risk, patients with other interstitial lung diseases, and normal healthy controls. BAL desmosine (pmol/100 microliters) was not significantly different in patients with ARDS (3.2, 2.1-3.0), patients at risk for ARDS (2.8, 2.5-4.4), and those with interstitial lung disease (3.0, 1.7-5.3) compared to normal controls (2.9, 1.9-4.7). There were poor correlations of BAL desmosine with physiologic indices of severity of disease in patients with ARDS and those at risk. Accelerated elastolysis occurred in the lower respiratory tract during the evaluation of bleomycin-induced pulmonary fibrosis in marmosets but was undetectable in BAL of patients studied within the first 3 days of ARDS.
Topics: Amino Acids; Animals; Bleomycin; Bronchoalveolar Lavage Fluid; Callithrix; Desmosine; Humans; Lung Diseases; Reference Values; Respiratory Distress Syndrome; Risk Factors
PubMed: 2478359
DOI: 10.3109/01902148909062858 -
The European Respiratory Journal May 2016Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease...
Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.
Topics: Adult; Aged; Biomarkers; Body Composition; Bronchodilator Agents; Calcinosis; Cardiovascular Diseases; Case-Control Studies; Coronary Vessels; Desmosine; Disease Progression; Elastin; Emphysema; Female; Forced Expiratory Volume; Humans; Inflammation; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Pulse Wave Analysis; Respiratory Function Tests; Risk Factors; Smoking; Vascular Stiffness
PubMed: 27009168
DOI: 10.1183/13993003.01824-2015 -
The International Journal of... Jun 2002An enhanced proteolysis of lung interstitium is key event in the pathogenesis of emphysema, a major constituent of chronic obstructive pulmonary disease. To assess... (Comparative Study)
Comparative Study
An enhanced proteolysis of lung interstitium is key event in the pathogenesis of emphysema, a major constituent of chronic obstructive pulmonary disease. To assess whether urinary desmosine and/or hydroxyproline may be used as a marker of lung destruction we studied urinary excretions of these products in 20 patients with chronic obstructive pulmonary disease and in 19 appropriate controls in 24h urine collection samples. For desmosine measurements, we developed a new indirect competitive enzyme-linked immunosorbent assay. The extent of emphysema was measured in high resolution computed tomography (CT) scans, by considering lung area with CT numbers <-950 Hounsfield units (HU). Urinary desmosine excretion was significantly higher in patients with chronic obstructive pulmonary disease than in controls (294+/-121 microg versus 183+/-93 microg, P=0.003), and was unrelated with both age and smoking habits. In patients with no evidence or only mild emphysema, desmosine excretion values were significantly higher (P=0.006) than those of patients with moderate to severe emphysema. In patients with chronic obstructive pulmonary disease, urinary hydroxyproline excretion was positively correlated with urinary desmosine excretion but on the average, it was not different from that of controls. These data indicate that urinary desmosine is a sensitive biological marker of lung elastin catabolism. The relatively low levels of urinary desmosine observed in patients with severe emphysema may be accounted for a decrease in elastin catabolism due to reduced lung elastin mass. Urinary desmosine may be used to identify subjects at risk of developing emphysema and to assess the efficacy of therapeutic interventions.
Topics: Adult; Aged; Biomarkers; Cohort Studies; Desmosine; Emphysema; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydroxyproline; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Respiratory Function Tests; Smoking; Tomography, X-Ray Computed
PubMed: 11943590
DOI: 10.1016/s1357-2725(02)00015-8 -
Chronic Obstructive Pulmonary Diseases... Mar 2016Desmosine (DES) and isodesmosine (IDES) have been widely discussed as potential biomarkers of COPD. However, their clinical utility and validity remains unproven. This...
Desmosine (DES) and isodesmosine (IDES) have been widely discussed as potential biomarkers of COPD. However, their clinical utility and validity remains unproven. 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. 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. Age, gender, body mass index (BMI) and smoking have a significant (<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 (<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. 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.
PubMed: 28848880
DOI: 10.15326/jcopdf.3.2.2015.0159 -
HSS Journal : the Musculoskeletal... Sep 2009Lung injury following total knee arthroplasty (TKA) may occur secondary to embolization of bone debris, fat, and cement. Clinically relevant respiratory failure is rare...
Lung injury following total knee arthroplasty (TKA) may occur secondary to embolization of bone debris, fat, and cement. Clinically relevant respiratory failure is rare and is therefore difficult to study. To facilitate future investigations on this subject, we evaluated the utility of the elastin breakdown product desmosine as a potential marker of lung injury during TKA surgery. The goals of this study were to answer (1) if desmosine levels would increase in response to the perioperative insults in patients undergoing TKA and (2) if this increase would differ among unilateral and bilateral TKA procedures. Twenty consecutive patients (ten unilateral and ten bilateral TKAs) were enrolled. Urine samples were collected before surgery and at 1 and 3 days postoperatively and analyzed for levels of desmosine using a validated radioimmunoassay. Baseline desmosine/creatinine ratios were higher in the unilateral as compared to the bilateral TKA group (p = 0.003). Tourniquet times, intraoperative estimated blood loss, and transfusion requirements among bilateral TKA patients were significantly higher than those of unilateral TKA recipients. Desmosine levels increased in both groups, but the rise was significant only in the bilateral group. We detected a significant increase in urine desmosine levels associated with bilateral but not unilateral TKA surgery. In the context of previous studies, our findings suggest that desmosine may be a marker of postoperative lung injury. Further research is warranted for validation and correlation of desmosine levels to clinical markers and various degrees of lung injury.
PubMed: 19521737
DOI: 10.1007/s11420-009-9116-9 -
Thorax Jun 2012Although an increased concentration of degraded elastin products in patients with chronic obstructive pulmonary disease (COPD) has been reported for many years, its... (Comparative Study)
Comparative Study
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.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Chromatography, Liquid; Desmosine; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Tandem Mass Spectrometry
PubMed: 22250098
DOI: 10.1136/thoraxjnl-2011-200279