Inflammatory Mediators Associated With Pressure Ulcer Development in Individuals With Pneumonia After Traumatic Spinal Cord Injury: A Pilot Study.

OBJECTIVE To identify the inflammatory mediators around the time of pneumonia onset associated with concurrent or later onset of pressure ulcers (PUs). DESIGN Retrospective. SETTING Acute hospitalization and inpatient rehabilitation unit of a university medical center. PARTICIPANTS Individuals (N=86) with traumatic spinal cord injury (SCI) were included in the initial analyses. Fifteen of the 86 developed pneumonia and had inflammatory mediator data available. Of these 15, 7 developed PUs and 8 did not. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Twenty-three inflammatory mediators in plasma and urine were assayed. The differences in concentrations of plasma and urine inflammatory mediators between the closest time point before and after the diagnosis of pneumonia were calculated. RESULTS Initial chi-square analysis revealed a significant (P=.02) association between pneumonia and PUs. Individuals with SCI and diagnosed pneumonia had nearly double the risk for developing PUs compared with those with no pneumonia. In individuals with pneumonia, Mann-Whitney U exact tests suggested an association (P<.05) between the formation of a first PU and a slight increase in plasma concentrations of tumor necrosis factor-alpha (TNF-α), and a decrease in urine concentrations of TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin (IL)-15 after onset of pneumonia. CONCLUSIONS These findings suggest that a relatively small increase in plasma TNF-α, and decreases in urine TNF-α, GM-CSF, and IL-15 from just before to just after the diagnosis of pneumonia could be markers for an increased risk of PUs in individuals with pneumonia after traumatic SCI.

[1]  T. Welte,et al.  Interleukin 6, lipopolysaccharide-binding protein and interleukin 10 in the prediction of risk and etiologic patterns in patients with community-acquired pneumonia: results from the German competence network CAPNETZ , 2012, BMC Pulmonary Medicine.

[2]  Graham Ramsay,et al.  Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: A randomized study* , 2006, Critical care medicine.

[3]  B. Dorner,et al.  The role of nutrition in pressure ulcer prevention and treatment: National Pressure Ulcer Advisory Panel white paper. , 2009, Advances in skin & wound care.

[4]  C. Oomens,et al.  Cytokine and chemokine release upon prolonged mechanical loading of the epidermis , 2007, Experimental dermatology.

[5]  K. Hayes,et al.  Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury. , 2007, Archives of physical medicine and rehabilitation.

[6]  W. Seeger,et al.  Expression of pro-inflammatory cytokines by flow-sorted alveolar macrophages in severe pneumonia. , 1998, The European respiratory journal.

[7]  W. Donovan,et al.  Neurologic recovery after traumatic spinal cord injury: data from the Model Spinal Cord Injury Systems. , 1999, Archives of physical medicine and rehabilitation.

[8]  John A Kellum,et al.  Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. , 2007, Archives of internal medicine.

[9]  D. Tate,et al.  Lifetime prevalence of chronic health conditions among persons with spinal cord injury. , 2015, Archives of physical medicine and rehabilitation.

[10]  T. Wiemken,et al.  Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of inflammatory response , 2015, Infection.

[11]  B. Kwon,et al.  Expression of inflammatory cytokines following acute spinal cord injury in a rodent model , 2012, Journal of neuroscience research.

[12]  P. D. de Leeuw,et al.  Prediction of clinical severity and outcome of ventilator-associated pneumonia. Comparison of simplified acute physiology score with systemic inflammatory mediators. , 1998, American journal of respiratory and critical care medicine.

[13]  Cees W J Oomens,et al.  Plasma variations of biomarkers for muscle damage in male nondisabled and spinal cord injured subjects. , 2012, Journal of rehabilitation research and development.

[14]  David J Margolis,et al.  Medical conditions as risk factors for pressure ulcers in an outpatient setting. , 2003, Age and ageing.

[15]  H. Alexander,et al.  Journal of Translational Medicine Interleukin-1 and Cancer Progression: the Emerging Role of Interleukin-1 Receptor Antagonist as a Novel Therapeutic Agent in Cancer Treatment , 2022 .

[16]  M. Stacey,et al.  Levels of Tumor Necrosis Factor-α (TNF-α) and Soluble TNF Receptors in Chronic Venous Leg Ulcers – Correlations to Healing Status , 1998 .

[17]  F. Adami,et al.  IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients , 2015, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[18]  J. Kopec,et al.  Impact of associated conditions resulting from spinal cord injury on health status and quality of life in people with traumatic central cord syndrome. , 2008, Archives of physical medicine and rehabilitation.

[19]  J. Van Damme,et al.  Macrophage inflammatory protein-1. , 2002, Cytokine & growth factor reviews.

[20]  H. Tilg,et al.  IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. , 1997, Immunology today.

[21]  L. Eng,et al.  Response of Chemokine Antagonists to Inflammation in Injured Spinal Cord , 2004, Neurochemical Research.

[22]  N. Stotts,et al.  Patients With Existing Pressure Ulcers Admitted to Acute Care , 2000, Journal of wound, ostomy, and continence nursing : official publication of The Wound, Ostomy and Continence Nurses Society.

[23]  C. Gabay,et al.  Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein. , 1997, The Journal of clinical investigation.

[24]  K. Stanley,et al.  Host biomarkers detected in saliva show promise as markers for the diagnosis of pulmonary tuberculosis disease and monitoring of the response to tuberculosis treatment. , 2016, Cytokine.

[25]  D. Langemo,et al.  National Pressure Ulcer Advisory Panel's Updated Pressure Ulcer Staging System , 2007, Dermatology nursing.

[26]  David R. Thomas,et al.  Prevention and treatment of pressure ulcers. , 2006, Journal of the American Medical Directors Association.

[27]  E. Calbo,et al.  The impact of time on the systemic inflammatory response in pneumococcal pneumonia , 2009, European Respiratory Journal.

[28]  J. Sanders,et al.  Skin response to repetitive mechanical stress: a new experimental model in pig. , 1998, Archives of physical medicine and rehabilitation.

[29]  M. Boninger,et al.  Association between presence of pneumonia and pressure ulcer formation following traumatic spinal cord injury , 2017, The journal of spinal cord medicine.

[30]  N. Higashi,et al.  Increased urinary leukotriene E4 concentration in patients with eosinophilic pneumonia , 2008, European Respiratory Journal.

[31]  Yannis Dionyssiotis Malnutrition in Spinal Cord Injury: More Than Nutritional Deficiency , 2012, Journal of clinical medicine research.

[32]  R. Janssen,et al.  Interleukin-15 is associated with disease severity in viral bronchiolitis , 2015, European Respiratory Journal.

[33]  J. Segal,et al.  Circulating levels of IL-2R, ICAM-1, and IL-6 in spinal cord injuries. , 1997, Archives of physical medicine and rehabilitation.

[34]  M. Post,et al.  Prevalence, location, grade of pressure ulcers and association with specific patient characteristics in adult spinal cord injury patients during the hospital stay: a prospective cohort study , 2013, Spinal Cord.

[35]  T. van der Poll,et al.  Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia. , 1997, The Journal of infectious diseases.

[36]  Huang-Pin Wu,et al.  Plasma transforming growth factor-beta1 level in patients with severe community-acquired pneumonia and association with disease severity. , 2009, Journal of the Formosan Medical Association = Taiwan yi zhi.

[37]  N. Al-Waili,et al.  Effects of Hyperbaric Oxygen on Inflammatory Response to Wound and Trauma: Possible Mechanism of Action , 2006, TheScientificWorldJournal.

[38]  L. Gould,et al.  Proteolytic activity in wound fluids and tissues derived from chronic venous leg ulcers , 2009, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[39]  M. Peters-Golden,et al.  GM-CSF Regulates Bleomycin-Induced Pulmonary Fibrosis Via a Prostaglandin-Dependent Mechanism , 2000, The Journal of Immunology.

[40]  M. Fujimoto,et al.  The loss of MCP-1 attenuates cutaneous ischemia-reperfusion injury in a mouse model of pressure ulcer. , 2008, The Journal of investigative dermatology.

[41]  Patricia Karg,et al.  Early Detection of Pressure Ulcer Development Following Traumatic Spinal Cord Injury Using Inflammatory Mediators. , 2016, Archives of physical medicine and rehabilitation.

[42]  Kath M Bogie,et al.  Pressure ulcer management and research priorities for patients with spinal cord injury: consensus opinion from SCI QUERI Expert Panel on Pressure Ulcer Research Implementation. , 2011, Journal of rehabilitation research and development.

[43]  J. Stechmiller,et al.  Effect of Vacuum‐Assisted Closure Therapy on the expression of cytokines and proteases in wound fluid of adults with pressure ulcers , 2006, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[44]  T. Marrie [Community acquired pneumonia]. , 1994, Praxis.

[45]  F. Arnold,et al.  Angiogenesis in wound healing. , 1991, Pharmacology & therapeutics.

[46]  A. Heinemann,et al.  Rehospitalization in the first year of traumatic spinal cord injury after discharge from medical rehabilitation. , 2013, Archives of physical medicine and rehabilitation.