Burn Injury Leads to Increased Long-Term Susceptibility to Respiratory Infection in both Mouse Models and Population Studies

Abstract

BackgroundBurn injury initiates an acute inflammatory response that subsequently drives wound repair. However, acute disruption to the immune response is also common, leading to susceptibility to sepsis and increased morbidity and mortality. Despite increased understanding of the impact of burn injury on the immune system in the acute phase, little is known about long-term consequences of burn injury on immune function. This study was established to determine whether burn injury has long-term clinical impacts on patients’ immune responses.MethodsUsing a population-based retrospective longitudinal study and linked hospital morbidity and death data from Western Australia, comparative rates of hospitalisation for respiratory infections in burn patients and a non-injured comparator cohort were assessed. In addition, a mouse model of non-severe burn injury was also used in which viral respiratory infection was induced at 4 weeks post-injury using a mouse modified version of the Influenza A virus (H3NN; A/mem/71-a).Results and conclusionsThe burn injured cohort contained 14893 adult patients from 1980–2012 after removal of those patients with evidence of smoke inhalation or injury to the respiratory tract. During the study follow-up study a total of 2,884 and 2,625 respiratory infection hospital admissions for the burn and uninjured cohorts, respectively, were identified. After adjusting for covariates, the burn cohort experienced significantly elevated admission rates for influenza and viral pneumonia (IRR, 95%CI: 1.73, 1.27–2.36), bacterial pneumonia (IRR, 95%CI: 2.05, 1.85–2.27) and for other types of upper and lower respiratory infections (IRR, 95% CI: 2.38, 2.09–2.71). In the mouse study an increased viral titre was observed after burn injury, accompanied by a reduced CD8 response and increased NK and NKT cells in the draining lymph nodes. This data suggests burn patients are at long-term increased risk of infection due to sustained modulation of the immune response.

Scald Injury-Induced T Cell Dysfunction Can Be Mitigated by Gr1+ Cell Depletion and Blockage of CD47/CD172a Signaling

“…Thus, our data indicates that burn victims could demonstrate reduced T cell functionality for well over 1 year following the injury. This is in line with population studies, which found that burn patients exhibited a heightened risk for respiratory infections in the first five years following burn injury (58). Given that the leading cause of burnrelated mortality are infections, this highlights the urgent need for clinical interventions (1).…”

Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response

“…Burns patients have a lifelong increase in the likelihood of developing a range of chronic inflammatory conditions (9)(10)(11)(12)(13)(14)35). The possibility of immune disruption in acute burn injuries, and more specifically severe burn trauma, has been extensively investigated.…”

“…In our laboratory pre-clinical studies in mice, modeling 8% TBSA involvement as a non-severe burn injury (NSBI), have demonstrated changes in innate and adaptive immunity up to 84 days post-injury (14,20). In pediatric patients with severe burn injury, sustained elevation of circulating cytokines has been observed up to 3 years after the injury (21).…”

Long-term mental health outcomes after unintentional burns sustained during childhood: a retrospective cohort study

“…In addition, cytokines and neuropeptides, such as oxytocin, are related to pain and psychological distress [ 53 , 54 ], and significant evidence suggests oxytocin has a neuromodulation role in (traumatic) stress and anxiety [ 53 , 55 ]. Evidence demonstrates that such systemic responses may occur after both severe and minor burns [ 56 – 59 ]. Given that the majority of paediatric burn admissions are for minor burns, these findings have important health implications.…”