Higher urine desmosine levels are associated with mortality in patients with acute lung injury

McClintock, Dana; Starcher, Barry; Eisner, Mark D.; Thompson, B. Taylor; Hayden, Doug; Church, Gwynne; Matthay, Michael A.

doi:10.1152/ajplung.00457.2005

Cited by 43 publications

(43 citation statements)

References 32 publications

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“…Further, this finding may mirror delayed breakdown of elastin after the initial insult to the lung and/or additional postoperative insults that lead to a protracted inflammatory response. Similar kinetics were found in a previous study of ARDS patients [12]. Further insight into the value of desmosine as a marker of pulmonary injury in our study may be provided by the observation that the patient with the highest urine desmosine to creatinine ratio after surgery had a history significant for preexisting pulmonary disease in the form of bronchiectasis and tuberculosis, suggesting increased vulnerability to secondary insults.…”

Section: Discussionsupporting

confidence: 87%

Urine Desmosine as a Marker of Lung Injury following Total Knee Arthroplasty. A Pilot Study

et al. 2009

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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.

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Section: Discussionsupporting

confidence: 87%

Urine Desmosine as a Marker of Lung Injury following Total Knee Arthroplasty. A Pilot Study

et al. 2009

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“…MV-O 2 treatment of patients with ARDS has been linked to pulmonary inflammation and increased elastolytic activity, resulting in breakdown of lung elastin and increased mortality (61)(62)(63). Consistent with this notion, a genome-wide expression analysis of blood samples taken from patients with ARDS showed a threefold decrease in the expression of peptidase inhibitor 3 (PI3, encoding elafin, a potent inhibitor of NE) during the acute phase compared with the recovery phase of the disease (64).…”

Section: Discussionmentioning

confidence: 77%

Inhibiting Lung Elastase Activity Enables Lung Growth in Mechanically Ventilated Newborn Mice

Hilgendorff

Parai²,

Ertsey³

et al. 2011

Am J Respir Crit Care Med

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Rationale: Mechanical ventilation with O 2 -rich gas (MV-O 2 ) offers life-saving treatment for respiratory failure, but also promotes lung injury. We previously reported that MV-O 2 of newborn mice increased lung elastase activity, causing elastin degradation and redistribution of elastic fibers from septal tips to alveolar walls. These changes were associated with transforming growth factor (TGF)-b activation and increased apoptosis leading to defective alveolarization and lung growth arrest, as seen in neonatal chronic lung disease. Objectives: To determine if intratracheal treatment of newborn mice with the serine elastase inhibitor elafin would prevent MV-O 2 -induced lung elastin degradation and the ensuing cascade of events causing lung growth arrest. Methods: Five-day-old mice were treated via tracheotomy with recombinant human elafin or vehicle (lactated-Ringer solution), followed by MV with 40% O 2 for 8-24 hours; control animals breathed 40% O 2 without MV. At study's end, lungs were harvested to assess key variables noted below. Measurements and Main Results: MV-O 2 of vehicle-treated pups increased lung elastase and matrix metalloproteinase-9 activity when compared with unventilated control animals, causing elastin degradation (urine desmosine doubled), TGF-b activation (pSmad-2 tripled), and apoptosis (cleaved-caspase-3 increased 10-fold). Quantitative lung histology showed larger and fewer alveoli, greater inflammation, and scattered elastic fibers. Elafin blocked these MV-O 2 -induced changes. Conclusions: Intratracheal elafin, by blocking lung protease activity, prevented MV-O 2 -induced elastin degradation, TGF-b activation, apoptosis, and dispersion of matrix elastin, and attenuated lung structural abnormalities noted in vehicle-treated mice after 24 hours of MV-O 2 . These findings suggest that elastin breakdown contributes to defective lung growth in response to MV-O 2 and might be targeted therapeutically to prevent MV-O 2 -induced lung injury.

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“…Using the same urine Cr measurements as in the current study, higher urine desmosine to Cr was predictive of worse outcomes. Moreover, desmosine levels rose in patients who died compared with those who survived by Day 3 (27). If the evaluation of desmosine and NO simply reflected the inverse of Cr, then the results in both studies should be comparable rather than divergent.…”

Section: Discussionmentioning

confidence: 96%

“…These patient samples were excluded from the analysis to avoid the hazards of imputing an arbitrary value to a sample that was not reliable for evaluation. The Cr results obtained were also used to evaluate urine desmosine in these patients; those results have been reported elsewhere (27). The ratio of urine NO to urine Cr (NO/Cr) was used in the statistical analyses to control for urine dilution, a standard method when evaluating urine biomarkers (28)(29)(30)(31).…”

Section: No and Cr Measurementsmentioning

confidence: 96%

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Higher Urine Nitric Oxide Is Associated with Improved Outcomes in Patients with Acute Lung Injury

McClintock

Ware

Eisner

et al. 2007

Am J Respir Crit Care Med

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Rationale: Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI). Objectives: We tested two hypotheses in patients with ALI: (1 ) higher levels of urine NO would be associated with worse clinical outcomes, and (2 ) ventilation with lower VT would reduce urine NO as a result of less stretch injury. Methods: Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg VT ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr). Results: Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 d), and more organ-failure-free days (mean increase, 2.3 d) on multivariate analysis (p Ͻ 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg VT group (p ϭ 0.04). Conclusions: Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg VT strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI.

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Higher urine desmosine levels are associated with mortality in patients with acute lung injury

Cited by 43 publications

References 32 publications

Urine Desmosine as a Marker of Lung Injury following Total Knee Arthroplasty. A Pilot Study

Urine Desmosine as a Marker of Lung Injury following Total Knee Arthroplasty. A Pilot Study

Inhibiting Lung Elastase Activity Enables Lung Growth in Mechanically Ventilated Newborn Mice

Higher Urine Nitric Oxide Is Associated with Improved Outcomes in Patients with Acute Lung Injury

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