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Critical Care
Published in: Critical Care 6/2011

Open Access 01-12-2011 | Research

Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study

Authors: Yara Backes, Koenraad F van der Sluijs, Anita M Tuip de Boer, Jorrit Jan Hofstra, Alexander PJ Vlaar, Rogier M Determann, Paul Knape, David P Mackie, Marcus J Schultz

Published in: Critical Care | Issue 6/2011

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Abstract

Introduction

Soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a biologic marker of fibrinolysis and inflammation. The aim of this study was to investigate the diagnostic and prognostic value of systemic and pulmonary levels of suPAR in burn patients with inhalation trauma who need mechanical ventilation.

Methods

suPAR was measured in plasma and nondirected lung-lavage fluid of mechanically ventilated burn patients with inhalation trauma. The samples were obtained on the day of inhalation trauma and on alternate days thereafter until patients were completely weaned from the mechanical ventilator. Mechanically ventilated patients without burns and without pulmonary disease served as controls.

Results

Systemic levels of suPAR in burn patients with inhalation trauma were not different from those in control patients. On admission and follow up, pulmonary levels of suPAR in patients with inhalation trauma were significantly higher compared with controls. Pulmonary levels of suPAR highly correlated with pulmonary levels of interleukin 6, a marker of inflammation, and thrombin-antithrombin complexes, markers of coagulation, but not plasminogen activator activity, a marker of fibrinolysis. Systemic levels of suPAR were predictive of the duration of mechanical ventilation and length of intensive care unit (ICU) stay. Duration of mechanical ventilation and length of ICU stay were significantly longer in burn-injury patients with systemic suPAR levels > 9.5 ng/ml.

Conclusions

Pulmonary levels of suPAR are elevated in burn patients with inhalation trauma, and they correlate with pulmonary inflammation and coagulation. Although pulmonary levels of suPAR may have diagnostic value in burn-injury patients, systemic levels of suPAR have prognostic value.
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Literature
1.
2.
Mizukami IF, Faulkner NE, Gyetko MR, Sitrin RG, Todd RF III: Enzyme-linked immunoabsorbent assay detection of a soluble form of urokinase plasminogen activator receptor in vivo. Blood 1995, 86: 203-211.PubMed
3.
Ostrowski SR, Ullum H, Goka BQ, Hoyer-Hansen G, Obeng-Adjei G, Pedersen BK, Akanmori BD, Kurtzhals JA: Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome. J Infect Dis 2005, 191: 1331-1341. 10.1086/428854CrossRefPubMed
4.
Perch M, Kofoed P, Fischer TK, Co F, Rombo L, Aaby P, Eugen-Olsen J: Serum levels of soluble urokinase plasminogen activator receptor are associated with parasitemia in children with acute Plasmodium falciparum malaria infection. Parasite Immunol 2004, 26: 207-211. 10.1111/j.0141-9838.2004.00695.xCrossRefPubMed
5.
Ostrowski SR, Piironen T, Hoyer-Hansen G, Gerstoft J, Pedersen BK, Ullum H: High plasma levels of intact and cleaved soluble urokinase receptor reflect immune activation and are independent predictors of mortality in HIV-1-infected patients. J Acquir Immune Defic Syndr 2005, 39: 23-31. 10.1097/01.qai.0000157950.02076.a6CrossRefPubMed
6.
Eugen-Olsen J, Gustafson P, Sidenius N, Fischer TK, Parner J, Aaby P, Gomes VF, Lisse I: The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau. Int J Tuberc Lung Dis 2002, 6: 686-692.PubMed
7.
Garcia-Monco JC, Coleman JL, Benach JL: Soluble urokinase receptor (uPAR, CD 87) is present in serum and cerebrospinal fluid in patients with neurologic diseases. J Neuroimmunol 2002, 129: 216-223. 10.1016/S0165-5728(02)00186-8CrossRefPubMed
8.
Ostergaard C, Benfield T, Lundgren JD, Eugen-Olsen J: Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. Scand J Infect Dis 2004, 36: 14-19. 10.1080/00365540310017366CrossRefPubMed
9.
Wittenhagen P, Kronborg G, Weis N, Nielsen H, Obel N, Pedersen SS, Eugen-Olsen J: The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality. Clin Microbiol Infect 2004, 10: 409-415. 10.1111/j.1469-0691.2004.00850.xCrossRefPubMed
10.
Koch A, Voigt S, Kruschinski C, Sanson E, Duckers H, Horn A, Yagmur E, Zimmermann H, Trautwein C, Tacke F: Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients. Crit Care 2011, 15: R63. 10.1186/cc10037PubMedCentralCrossRefPubMed
11.
Moller HJ, Moestrup SK, Weis N, Wejse C, Nielsen H, Pedersen SS, Attermann J, Nexø E, Kronborg G: Macrophage serum markers in pneumococcal bacteremia: prediction of survival by soluble CD163. Crit Care Med 2006, 34: 2561-2566. 10.1097/01.CCM.0000239120.32490.ABCrossRefPubMed
12.
Huttunen R, Syrjanen J, Vuento R, Hurme M, Huhtala H, Laine J, Pessi T, Aittoniemi J: Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study. J Intern Med 2011, in press.
13.
Kofoed K, Eugen-Olsen J, Petersen J, Larsen K, Andersen O: Predicting mortality in patients with systemic inflammatory response syndrome: an evaluation of two prognostic models, two soluble receptors, and a macrophage migration inhibitory factor. Eur J Clin Microbiol Infect Dis 2008, 27: 375-383. 10.1007/s10096-007-0447-5CrossRefPubMed
14.
Thompson PB, Herndon DN, Traber DL, Abston S: Effect on mortality of inhalation injury. J Trauma 1986, 26: 163-165. 10.1097/00005373-198602000-00012CrossRefPubMed
15.
Suzuki M, Aikawa N, Kobayashi K, Higuchi R: Prognostic implications of inhalation injury in burn patients in Tokyo. Burns 2005, 31: 331-336. 10.1016/j.burns.2004.10.016CrossRefPubMed
16.
Saffle JR, Davis B, Williams P: Recent outcomes in the treatment of burn injury in the United States: a report from the American Burn Association Patient Registry. J Burn Care Rehabil 1995, 16: 219-232. 10.1097/00004630-199505000-00002CrossRefPubMed
17.
Shirani KZ, Pruitt BA Jr, Mason AD Jr: The influence of inhalation injury and pneumonia on burn mortality. Ann Surg 1987, 205: 82-87. 10.1097/00000658-198701000-00015PubMedCentralCrossRefPubMed
18.
Marek K, Piotr W, Stanislaw S, Stefan G, Justyna G, Mariusz N, Andriessen A: Fibreoptic bronchoscopy in routine clinical practice in confirming the diagnosis and treatment of inhalation burns. Burns 2007, 33: 554-560. 10.1016/j.burns.2006.08.030CrossRefPubMed
19.
Ambiavagar M, Chalon J, Zargham I: Tracheobronchial cytologic changes following lower airway thermal injury: a preliminary report. J Trauma 1974, 14: 280-289. 10.1097/00005373-197404000-00002CrossRefPubMed
20.
Woodson LC: Diagnosis and grading of inhalation injury. J Burn Care Res 2009, 30: 143-145. 10.1097/BCR.0b013e3181923b71CrossRefPubMed
21.
Hofstra JJ, Vlaar AP, Knape P, Mackie DP, Determann RM, Choi G, van der Poll T, Levi M, Schultz MJ: Pulmonary activation of coagulation and inhibition of fibrinolysis after burn injuries and inhalation trauma. J Trauma 2011, 70: 1389-1397. 10.1097/TA.0b013e31820f85a7CrossRefPubMed
22.
Schultz MJ, Haitsma JJ, Zhang H, Slutsky AS: Pulmonary coagulopathy as a new target in therapeutic studies of acute lung injury or pneumonia: a review. Crit Care Med 2006, 34: 871-877.PubMed
23.
Millo JL, Schultz MJ, Williams C, Weverling GJ, Ringrose T, Mackinlay CI, van der Poll T, Garrard CS: Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia. Intensive Care Med 2004, 30: 68-74. 10.1007/s00134-003-2060-0CrossRefPubMed
24.
Murray JF, Matthay MA, Luce JM, Flick MR: An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988, 138: 720-723.CrossRefPubMed
25.
Thomas NJ, Shaffer ML, Willson DF, Shih MC, Curley MA: Defining acute lung disease in children with the oxygenation saturation index. Pediatr Crit Care Med 2010, 11: 12-17. 10.1097/PCC.0b013e3181b0653dPubMedCentralCrossRefPubMed
26.
Herndon DN, Traber DL, Niehaus GD, Linares HA, Traber LD: The pathophysiology of smoke inhalation injury in a sheep model. J Trauma 1984, 24: 1044-1051. 10.1097/00005373-198412000-00007CrossRefPubMed
27.
28.
Gore MA, Joshi AR, Nagarajan G, Iyer SP, Kulkarni T, Khandelwal A: Virtual bronchoscopy for diagnosis of inhalation injury in burnt patients. Burns 2004, 30: 165-168. 10.1016/j.burns.2003.09.024CrossRefPubMed
29.
Fujitani S, Yu VL: Diagnosis of ventilator-associated pneumonia: focus on nonbronchoscopic techniques (nonbronchoscopic bronchoalveolar lavage, including mini-BAL, blinded protected specimen brush, and blinded bronchial sampling) and endotracheal aspirates. J Intensive Care Med 2006, 21: 17-21. 10.1177/0885066605283094CrossRefPubMed
30.
Eugen-Olsen J: suPAR: a future risk marker in bacteremia. J Intern Med 2011, 270: 29-31. 10.1111/j.1365-2796.2011.02372.xCrossRefPubMed
31.
Kofoed K, Schneider UV, Scheel T, Andersen O, Eugen-Olsen J: Development and validation of a multiplex add-on assay for sepsis biomarkers using xMAP technology. Clin Chem 2006, 52: 1284-1293. 10.1373/clinchem.2006.067595CrossRefPubMed
32.
Molkanen T, Ruotsalainen E, Thorball CW, Jarvinen A: Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 2011, 30: 1417-1424. 10.1007/s10096-011-1236-8CrossRefPubMed
33.
Bugge TH, Flick MJ, Danton MJ, Daugherty CC, Romer J, Dano K, Carmeliet P, Collen D, Degen JL: Urokinase-type plasminogen activator is effective in fibrin clearance in the absence of its receptor or tissue-type plasminogen activator. Proc Natl Acad Sci USA 1996, 93: 5899-5904. 10.1073/pnas.93.12.5899PubMedCentralCrossRefPubMed
34.
Mondino A, Blasi F: uPA and uPAR in fibrinolysis, immunity and pathology. Trends Immunol 2004, 25: 450-455. 10.1016/j.it.2004.06.004CrossRefPubMed
35.
Rijneveld AW, Levi M, Florquin S, Speelman P, Carmeliet P, van Der Poll T: Urokinase receptor is necessary for adequate host defense against pneumococcal pneumonia. J Immunol 2002, 168: 3507-3511.CrossRefPubMed
36.
Ossowski L, Aguirre-Ghiso JA: Urokinase receptor and integrin partnership: coordination of signaling for cell adhesion, migration and growth. Curr Opin Cell Biol 2000, 12: 613-620. 10.1016/S0955-0674(00)00140-XCrossRefPubMed
37.
May AE, Kanse SM, Lund LR, Gisler RH, Imhof BA, Preissner KT: Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo. J Exp Med 1998, 188: 1029-1037. 10.1084/jem.188.6.1029PubMedCentralCrossRefPubMed
38.
Resnati M, Guttinger M, Valcamonica S, Sidenius N, Blasi F, Fazioli F: Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect. EMBO J 1996, 15: 1572-1582.PubMedCentralPubMed
39.
Selleri C, Montuori N, Ricci P, Visconte V, Carriero MV, Sidenius N, Serio B, Blasi F, Rotoli B, Rossi G, Ragno P: Involvement of the urokinase-type plasminogen activator receptor in hematopoietic stem cell mobilization. Blood 2005, 105: 2198-2205. 10.1182/blood-2004-06-2424CrossRefPubMed
40.
Choi G, Schultz MJ, Levi M, van der Poll T: The relationship between inflammation and the coagulation system. Swiss Med Wkly 2006, 136: 139-144.PubMed
41.
42.
Dixon B, Schultz MJ, Smith R, Fink JB, Santamaria JD, Campbell DJ: Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomized controlled trial. Crit Care 2010, 14: R180. 10.1186/cc9286PubMedCentralCrossRefPubMed
43.
Miller AC, Rivero A, Ziad S, Smith DJ, Elamin EM: Influence of nebulized unfractionated heparin and N -acetylcysteine in acute lung injury after smoke inhalation injury. J Burn Care Res 2009, 30: 249-256. 10.1097/BCR.0b013e318198a268CrossRefPubMed
44.
Eugen-Olsen J, Andersen O, Linneberg A, Ladelund S, Hansen TW, Langkilde A, Petersen J, Pielak T, Møller LN, Jeppesen J, Lyngbaek S, Fenger M, Olsen MH, Hildebrandt PR, Borch-Johnsen K, Jørgensen T, Haugaard SB: Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J Intern Med 2010, 268: 296-308. 10.1111/j.1365-2796.2010.02252.xCrossRefPubMed
Metadata
Title
Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study
Authors
Yara Backes
Koenraad F van der Sluijs
Anita M Tuip de Boer
Jorrit Jan Hofstra
Alexander PJ Vlaar
Rogier M Determann
Paul Knape
David P Mackie
Marcus J Schultz
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Critical Care / Issue 6/2011
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc10550

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