Relationship Between Neutrophil Function and Sepsis in Adults and Children With Severe Thermal Injuries

Study Overview
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Brief Summary
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The study aims to validate neutrophil function, immature granulocyte and plasma free DNA levels as predictive diagnostic biomarkers of sepsis in burn patients. Inclusion criteria includes healthy volunteers, patients aged 5-15 years old with burns affecting 20% or less Total Body Surface Area (TBSA) and patients aged 16 or above with burns affecting >15% TBSA. The study involves taking blood, tissue and urine samples.

Detailed Description
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The initial cohort for SIFTI-2 will be generated from patients attending the Birmingham Burns Centre at Queen Elizabeth Hospital Birmingham (QEHB) and Birmingham Children's Hospital (BCH). The cohort will be comprised of patients with moderate and severe burns (injury to more than 15% of the body surface area [TBSA] in adults and 20% TBSA in children). The investigators currently treat between 30-40 patients in this category each year. In order to thoroughly characterise the longitudinal neutrophil response to burn injury and to investigate its potential relationship with outcome post-burn, the ivestigators will measure the genomic, phenotypic and functional response of peripheral blood neutrophils across time in burn-injured patients.

Official Title
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A Multi-centre, Prospective Study to Examine the Relationship Between Neutrophil Function and Sepsis in Adults and Children With Severe Thermal Injuries

Conditions
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Burns

Intervention / Treatment
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* Other: taking of blood, urine and blood samples and objective scar assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 1-15 years admitted with a ≥20%TBSA Patients aged 16 and over admitted with a ≥15% TBSA Patients presented within 24 hours of thermal injury Exclusion Criteria: Associated multiple injuries with Injury severity score > 25 Decision not to treat made on admission due to the severity of the injury Patients with chemical and deep electrical burns Premorbid conditions Active Malignancy Patients receiving glucocorticoid treatment Multiple limb amputations Patients with known long term infections (i.e., Hepatitis B & C, Human Immune Deficiency [HIV])

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Burn patients<br>with the condition | Other: taking of blood, urine and blood samples and objective scar assessment<br>* blood, urine and skin tissue sampling & scar assessment questionnaires<br>|
| Control group<br>without the condition (blood sampling only for adults) and children undergoing general anaesthetic procedures that involve skin resections (blood sampling and excised skin) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of sepsis | Sepsis will be evaluated according to the 2007 American Burn Association (ABA) diagnostic criteria for sepsis in burns. Specifically, sepsis will be diagnosed when 3 of the following criteria are met along with a positive bacterial culture or when evidence of a clinical response to antibiotics is detected: Temperature (>39°C or <36°C) progressive tachycardia (>110 beats per minute progressive tachypnea (>25 breaths per minute not ventilated or minute ventilation >12 L/minute ventilated) thrombocytopenia (<100,000/μl; not applied until 3 days after initial resuscitation) hyperglycaemia (untreated plasma glucose >200 mg/dl, >7 units of insulin/hr intravenous drip, or >25% increase in insulin requirements over 24 hours) feed intolerance >24 hours (abdominal distension, residuals two times the feeding rate, or diarrhoea >2500 ml/day) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital mortality | Death while in-hospital | 2 years | 
| Predictive mortality scores | Predictive mortality scores are measured by Revised Baux Score, Abbreviated Burn Severity Index (ABSI), and APACHE II | 2 years | 
| Multiple Organ Failure/dysfunction syndrome (MOF/MODS) | The presence of altered organ function where homeostasis cannot be maintained without intervention using Denver 2 and SOFA scores. For Denver score, MOF is defined as > 3, two (2) organ system involved for 2 consecutive days while in SOFA, MOF> = 4 , two (2) organ system involved for first 24 hours. In the subsequent time points, only cardiac scores for SOFA and Denver 2 are recorded. | 2 years | 
| Thromboembolic complications | Clinical signs and symptoms associated with thrombosis, i.e., pulmonary embolism, deep vein thrombosis. Clinical investigation to confirm thrombosis will be based on any of the following imaging procedure: CTPA, VQ Scan, USS, Venogram, D-dimer results | 2 years | 
| Vancouver Scar Scale (VSS) | This scale uses a numerical assessment of four skin characteristics including: Height (range, 0-4), Pliability (range, 0-4), Vascularity (range, 0-3), and Pigmentation (range, 0-3). The assessors choose a numerical value for each of these characteristics based on a comparison with normal skin. | 2 years | 
| Patient and Observer Scar Assessment Scale | Patient and Observer Scar Assessment Scale (POSAS, version 2.0) - The POSAS questionnaire seeks to measure scar quality and is a subjective scar scale that consists of two parts: a Patient Scale and an Observer Scale. Both scales contain six items that are scored numerically on a ten-step scale and together they make up the 'Total Score' of the Patient and Observer Scale. The POSAS Patient scale assesses the scar in terms of pain, itching, scar colour, stiffness, thickness and irregularity and overall opinion. The POSAS Observer scale assesses the scar in terms of vascularity, pigmentation, thickness, relief, pliability, surface area and overall opinion. | 2 years | 
| Brisbane Burn Scar Impact Profile | Brisbane Burn Scar Impact Profile (BBSIP, version 1.0) - This questionnaire assesses the health-related quality of life in people with burn scars. It consists of seven parts which measure; (a) the overall impact of burn scars (itch, pain and other sensations, and their impact on the subject), (b) the impact of the burn scars on work and daily activities, (c) the impact of the burn scars on relationships and social interactions, (d) the subjects perception of the impact of the burn scars on their appearance, (e) the subjects emotional reactions towards their scars and (f) the physical symptoms caused by the burn scars. | 2 years |