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Heparin-binding protein (HBP): an early marker of respiratory failure after trauma?
Ostersund Hospital, Sweden .
Karolinska Institute, Sweden .
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
Karolinska Institute, Sweden .
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2013 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 5, 580-586 p.Article in journal (Refereed) Published
Abstract [en]

Background Trauma and its complications contribute to morbidity and mortality in the general population. Trauma victims are susceptible to acute respiratory distress syndrome (ARDS) and sepsis. Polymorphonuclear leucocytes (PMNs) are activated after trauma and there is substantial evidence of their involvement in the development of ARDS. Activated PMNs release heparin-binding protein (HBP), a granule protein previously shown to be involved in acute inflammatory reactions. We hypothesised that there is an increase in plasma HBP content after trauma and that the increased levels are related to the severity of the trauma or later development of severe sepsis and organ failure (ARDS). Methods and Material We investigated HBP in plasma samples within 36h from trauma in 47 patients admitted to a level one trauma centre with a mean injury severity score (ISS) of 26 (2134). ISS, admission sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were recorded at admission. ARDS and presence of severe sepsis were determined daily during intensive care. Results We found no correlation between individual maximal plasma HBP levels at admission and ISS, admission SOFA or APACHE II. We found, however, a correlation between HBP levels and development of ARDS (P=0.026, n=47), but not to severe sepsis. Conclusion HBP is a potential biomarker candidate for early detection of ARDS development after trauma. Further research is required to confirm a casual relationship between plasma HBP and the development of ARDS.

Place, publisher, year, edition, pages
Wiley-Blackwell , 2013. Vol. 57, no 5, 580-586 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-92696DOI: 10.1111/aas.12070ISI: 000317432300006OAI: diva2:621670

Funding Agencies|Research and Development Unit, Jamtland County Council||Laerdal Foundation||Magn Bergvalls Foundation||LPS Medical Foundation||Cancer and Traffic Injury Fund||Carnegie Foundation||Karolinska Institutet||Swedish Society of Medicine||Stockholm County Council||

Available from: 2013-05-16 Created: 2013-05-16 Last updated: 2014-03-24
In thesis
1. Function of granulocytes after burns and trauma, associations with pulmonary vascular permeability, acute respiratory distress syndrome, and immunomodulation
Open this publication in new window or tab >>Function of granulocytes after burns and trauma, associations with pulmonary vascular permeability, acute respiratory distress syndrome, and immunomodulation
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Our innate immunesystem protects us from infections but, since its methods is not all specific for microorganisms, may also induce collateral damage.

Severe physical injury often proved deadly throughout evolution. Such injuries may induce massive collateral damage. Nowadays we can initiate advanced critical care for affected patients and save them from imminent trauma-related death. We are therefore faced with the fact that the collateral damage from the immune system may pose a major threat to the patient, the pathophysiology of which is not amenable to direct medical treatment and which leaves us with only passive supportive measures.

In this thesis we investigated the role of leucocytes under such circumstances.

Our main aim was to understand better the role of leucocytes in the development of increased vascular permeability after burns and trauma.

More specifically we investigated the impact of an injury on the function of leucocytes such as the dynamic change of certain cell-surface receptors on the leucocytes and in their numbers and immature forms. We wanted to find out if the increased pulmonary vascular permeability after a burn could be mediated through heparin binding protein (HBP) released from granuloctes, and whether HBP could be used as a biomarker for respiratory failure after trauma. We also wanted to confirm the possible role of histamine as a mediator of the systemic increase in vascular permeability after burns.

Methods: The dynamic change of cell-surface receptors was measured by flow-acquired cytometer scanning (FACS) on blood samples taken after burns. The concentrations of HBP after a burn and mechanical trauma were analysed in plasma. Pulmonary vascular permeability after a burn was assessed using transpulmonary thermodilution. The histamine turnover after a burn was assessed with high performance liquid chromatography (HPLC) for concentrations of histamine and methylhistamine in urine.

Results: We confirmed earlier investigations showing altered expression of receptors on leucocytes after a burn, receptors intimately associated with leucocyte functions (study I). In a pilot study of 10 patients we measured plasma concentrations of HBP and found them to be increased soon after a burn (study II). This finding was not confirmed in a larger, more extensive and specific study of 20 patients. We did, however, find an association between alterations in the number of leucocytes soon after a burn and pulmonary vascular permeability, indicating that they had a role in this process (study III).

In another study of trauma (non burn) we found an association between the concentration of HBP in early plasma-samples after injury and the development of ARDS, indicating that granulocytes and HBP have a role in its aetiology (study IV).

We found a small increase in urinary histamine and normal urinary methylhistamine concentrations but had anticipated a distinct increase followed by a decrease after reading the current papers on the subject. This indicates that the role of histamine as a mediator of increased vascular permeability after burns may have been exaggerated (study V).

Conclusions: We conclude that leucocytes are affected by burns and trauma, and it is likely that they contribute to the development of respiratory failure and acute respiratory distress syndrome (ARDS). HBP is a candidate biomarker for the early detection of ARDS after trauma, and the white blood count (WBC) is a useful biomarker for the detection of decreased oxygenation soon after a burn.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 72 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1362
ARDS, azurocidin, burn, CAP-37, critical care, granulocyte, HBP, histamine, intensive care, leucocyte, leukocyte, mediator, methylhistamine, MOF, oedema, neutrophil, permeability, PMN, trauma, vascular permeability
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-94513 (URN)978-91-7519-632-9 (print) (ISBN)
Public defence
2013-09-05, Elsa Brändström salen, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Available from: 2013-06-25 Created: 2013-06-25 Last updated: 2014-03-24Bibliographically approved

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Sjöberg, Folke
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Division of Clinical SciencesFaculty of Health SciencesDepartment of Hand and Plastic SurgeryDepartment of Anaesthesiology and Intensive Care in Linköping
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