Metabolic Phenotyping the Acute Phase of Burn Injury in Children

Chloe L Scott

Burn injuries in paediatric patients have been shown to pose significant long-term health risks. Yet, limited knowledge exists on the metabolic changes that occur during the acute phase (up to 14 days post injury) and post-burn recovery. This thesis investigates the metabolic changes that occur in a paediatric cohort's acute phase of burn injury. In addition, metabolic changes were investigated over 1-year post-burn injury to determine recovery time and identify any metabolites that may remain perturbed following injury. Blood plasma samples were collected from paediatric patients that had an acute burn injury (n=232), and a control group of healthy children (n=53). 1H NMR spectroscopy was used to quantify small molecule metabolites (n=25), lipoproteins (n=112), and inflammatory markers (n=6). Multivariate analysis was used to determine metabolic disturbances across acute burn injury compared to the healthy control group, as well as determining differences during recovery and 1-year post-injury. In acute burn injury patients, it was found 23 small molecule metabolites, 60 lipoproteins and 5 inflammatory markers were perturbed (p-value< 0.05) when compared to the healthy control cohort. One of the most highly elevated lipoprotein parameters is the ratio Apolipoprotein B100/A1 ratio (p-value=6.54x10-7), a reported marker of atherosclerotic risk. While tyrosine (p-value=1.10x10-14), glutamine (p-value=7.54x10-14) and alanine (p-value=1.98x10-11) are reduced and the inflammatory markers GlycA (p-value=1.67x10-8) and GlycB (pvalue= 5.74x10-9) were elevated. The continued monitoring of the burn injury patient’s postacute injury phase indicates that while many of the metabolites return to the level considered normal, some, for example, SPC2, take over 1-year post-injury to normalise, while others remain perturbed. It was also found a subset of VLDL subfractions that were not perturbed at acute injury became significantly different at 1 year post burn injury. The metabolic disruption at the time of acute burn injury is indicative of a highly inflamed state, and this research highlights a crucial need for long term monitoring of children even when the burn injury scar is considered recovered, to minimise the long-term health burden for paediatric burn survivors that has been suggested within the literature.

Metabolic Phenotyping the Acute Phase of Burn Injury in Children

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