title: Burn Injury Leads to Increased Long-Term Susceptibility to Respiratory Infection in both Mouse Models and Population Studies.
abstract: BACKGROUND
  Burn 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.
  
  
  METHODS
  Using 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Tumour Immunology Group, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.|Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: Fear
authors.affiliation: Centre for Data Linkage, Curtin University, Perth, Western Australia, Australia.
authors.forename: James H
authors.initials: JH
authors.lastname: Boyd
authors.affiliation: Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia.|Burns Service of Western Australia, Fiona Stanley Hospital and Princess Margaret Hospital, Perth, Western Australia, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Rea
authors.affiliation: Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia.|Burns Service of Western Australia, Fiona Stanley Hospital and Princess Margaret Hospital, Perth, Western Australia, Australia.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Wood
authors.affiliation: Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Janine M
authors.initials: JM
authors.lastname: Duke
authors.affiliation: Burn Injury Research Unit, School of Surgery, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Mark W
authors.identifier: http://orcid.org/0000-0003-3163-4666
authors.initials: MW
authors.lastname: Fear
mesh_terms: D000328:Adult; D000818:Animals; D002056:Burns / Q000150:complications*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D006304:Health Status; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D011159:Population Surveillance; D012141:Respiratory Tract Infections / Q000453:epidemiology* / Q000209:etiology*; D014904:Western Australia / Q000453:epidemiology