Plasma lipidomics reveal systemic changes persistent throughout early life following a childhood burn injury

Background:Non-severe paediatric burns can result in poor long-term health outcomes.This occurs even in cases with good acute burn-related outcomes,including minimal scarring.The mechanisms that underpin the transition from non-severe burn to sustained negative long-term health impacts are currently unknown.However,sustained metabolic and immune changes have been observed in paediatric burn studies,suggesting these changes may be important.The plasma lipidome consists of a rich pool of bioactive metabolites that play critical roles in systemic processes including molecular signalling and inflammation.We hypothesised that changes in the plasma lipidome may reflect underlying changes in health status and be linked to long-term health after burn trauma.Methods:This study analysed the lipidome in children who had previously experienced a non-severe burn,compared to non-injured controls.Thirty-three participants were recruited between the ages of 5 and 8 years who had experienced a non-severe burn between the ages of 1 and 3 years.Plasma samples were also collected from a non-injured,healthy,age and gender matched control group(n=21).Plasma lipids were measured using reversed-phase liquid chromatographymass spectrometery(LC-MS).Results:In total 838 reproducible lipid species from 19 sub-classes passed quality control procedures and progressed to statistical analysis.Analysis of individual lipid metabolites showed significantly higher concentrations of lysophosphatidylethanolamines and phosphatidylethanolamines,and significantly lower concentrations in myristic,palmitic and palmitoleic acids in the plasma of those who had experienced burn injury compared to controls.Conclusion:Long-term changes in the lipid profile may give insight into the mechanisms underlying poor long-term health subsequent to non-severe burn injury.Further work to investigate the relationship between long-term pathology and lipidomic changes may lead to a better understanding of the causes of secondary morbidity post-burn and to clinical intervention to reduce the long-term health burden of burn trauma.

Understanding acute burn injury as a chronic disease

While treatment for burn injury has improved significantly over the past few decades,reducing mortality and improving patient outcomes,recent evidence has revealed that burn injury is associated with a number of secondary pathologies,many of which arise long after the initial injury has healed.Population studies have linked burn injury with increased risk of cancer,cardiovascular disease,nervous system disorders,diabetes,musculoskeletal disorders,gastrointestinal disease,infections,anxiety and depression.The wide range of secondary pathologies indicates that burn can cause sustained disruption of homeostasis,presenting new challenges for post-burn care.Understanding burn injury as a chronic disease will improve patient care,providing evidence for better long-term support and monitoring of patients.Through focused research into the mechanisms underpinning long-term dysfunction,a better understanding of burn injury pathology may help with the development of preventative treatments to improve long-term health outcomes.The review will outline evidence of long-term health effects,possible mechanisms linking burn injury to long-term health and current research into burns as a chronic disease.

Non-severe burn injury increases cancer incidence in mice and has long-term impacts on the activation and function of T cells

Background:Recent evidence suggests that burn patients are at increased risk of hospital admission for infection,mental health conditions,cardiovascular disease and cancer for many years after discharge for the burn injury itself.Burn injury has also been shown to induce sustained immune system dysfunction.This change to immune function may contribute to the increased risk of chronic disease observed.However,the mechanisms that disrupt long-term immune function in response to burn trauma,and their link to long-term morbidity,remain unknown.In this study we investigated changes to immune function after burn injury using a murine model of non-severe injury.Methods:An established mouse model of non-severe burn injury(full thickness burn equivalent to 8%total body surface area)was used in combination with an orthotopic model of B16 melanoma to investigate the link between burns and cancer.Considering that CD8^(+)T cells are important drivers of effective tumour suppression in this model,we also investigated potential dysregulation of this immune population using mouse models of burn injury in combination with herpes simplex virus infection.Flow cytometry was used to detect and quantify cell populations of interest and changes in immune function.Results:We demonstrate that 4 weeks after a non-severe burn injury,mice were significantly more susceptible to tumour development than controls using an orthotopic model of B16 melanoma.In addition,our results reveal that CD8^(+)T cell expansion,differentiation and memory potential is significantly impaired at 1 month post-burn.Conclusions:Our data suggests that CD8^(+)T cell-mediated immunity may be dysfunctional for a sustained period after even non-severe burn injury.Further studies in patients to validate these findings may support clinical intervention to restore or protect immunity in patients after burn injury and reduce the increased risk of secondary morbidities observed.

A retrospective cohort study to compare post-injury admissions for infectious diseases in burn patients, non-burn trauma patients and uninjured people

Background: Injury triggers a range of systemic effects including inflammation and immune responses. This study aimed to compare infectious disease admissions after burn and other types of injury using linked hospital admissions data. Methods: A retrospective longitudinal study using linked health data of all patients admitted with burns in Western Australia (n = 30,997), 1980–2012, and age and gender frequency matched cohorts of people with non-burn trauma (n = 28,647) and no injury admissions (n = 123,399). Analyses included direct standardisation, negative binomial regression and Cox proportional hazards regression. Results: Annual age-standardised infectious disease admission rates were highest for the burn cohort, followed by the non-burn trauma and uninjured cohorts. Age-standardised admission rates by decade showed different patterns across major categories of infectious diseases, with the lower respiratory and skin and soft tissue infections the most common for those with burns and other open trauma. Compared with the uninjured, those with burns had twice the admission rate for infectious disease after discharge (incident rate ratio (IRR), 95% confidence interval (CI): 2.04, 1.98–2.11) while non-burn trauma experienced 1.74 times higher rates (95%CI: 1.68–1.81). The burn cohort experienced 10% higher rates of first-time admissions after discharge when compared with the non-burn trauma (hazard ratio (HR), 95%CI: 1.10, 1.05–1.15). Compared with the uninjured cohort, incident admissions were highest during the first 30 days after discharge for burns (HR, 95%CI: 5.18, 4.15–6.48) and non-burn trauma (HR, 95%CI: 5.06, 4.03–6.34). While incident rates remained high over the study period, the magnitude decreased with increasing time from discharge: burn vs uninjured: HR, 95%CI: 30 days to 1 year: 1.69, 1.53–1.87;1 to 10 years: 1.40, 1.33–1.47;10 years to end of study period: 1.16, 1.08–1.24;non-burn trauma vs uninjured: HR, 95%CI: 30 days to 1 year: 1.71, 1.55–1.90;1 to 10 years: 1.30, 1.24–1.37;10 years to end of study period: 1.09, 1.03–1.17). Conclusions: Burns and non-burn trauma patients had higher admission rates for infectious diseases compared with age and gender matched uninjured people. The pattern of annual admission rates for major categories of infectious diseases varied across injury groups. Overal , the burn cohort experienced the highest rates for digestive, lower respiratory and skin and soft tissue infections. These results suggest long-term vulnerability to infectious disease after injury, possibly related to long-term immune dysfunction.