Inhalation injury severity and systemic immune perturbations in burned adults

Abstract

Objective: We aimed to determine whether the severity of inhalation injury evokes an immune response measurable at the systemic level and to further characterize the balance of systemic pro- and anti-inflammation early after burn and inhalation injury.

Background: Previously, we reported that the pulmonary inflammatory response is enhanced with worse grades of inhalation injury and that those who die of injuries have a blunted pulmonary immune profile compared with survivors.

Methods: From August 2007 to June 2011, bronchoscopy was performed on 80 patients admitted to the burn intensive care unit when smoke inhalation was suspected. Of these, inhalation injury was graded into 1 of 5 categories (0, 1, 2, 3, and 4), with grade 0 being the absence of visible injury and grade 4 corresponding to massive injury. Plasma was collected at the time of bronchoscopy and analyzed for 28 immunomodulating proteins via multiplex bead array or enzyme-linked immunosorbent assay.

Results: The concentrations of several plasma immune mediators were increased with worse inhalation injury severity, even after adjusting for age and % total body surface area (TBSA) burn. These included interleukin (IL)-1RA (P = 0.002), IL-6 (P = 0.002), IL-8 (P = 0.026), granulocyte colony-stimulating factor (P = 0.002), and monocyte chemotactic protein 1 (P = 0.007). Differences in plasma immune mediator concentrations in surviving and deceased patients were also identified. Briefly, plasma concentrations of IL-1RA, IL-6, IL-8, IL-15, eotaxin, and monocyte chemotactic protein 1 were higher in deceased patients than in survivors (P < 0.05 for all), whereas IL-4 and IL-7 were lower (P < 0.05). After adjusting for the effects of age, % TBSA burn, and inhalation injury grade, plasma IL-1RA remained significantly associated with mortality (odds ratio, 3.12; 95% confidence interval, 1.03-9.44). Plasma IL-1RA also correlated with % TBSA burn, inhalation injury grade, fluid resuscitation, Baux score, revised Baux score, Denver score, and the Sequential Organ Failure Assessment score.

Conclusions: The severity of smoke inhalation injury has systemically reaching effects, which argue in favor of treating inhalation injury in a graded manner. In addition, several plasma immune mediators measured early after injury were associated with mortality. Of these, IL-1RA seemed to have the strongest correlation with injury severity and outcomes measures, which may explain the blunted pulmonary immune response we previously found in nonsurvivors.

Figure 1

Comparison of clinical parameters and outcomes measures between surviving and deceased patients of combined burn and smoke inhalation injury. Age (A), % TBSA (B), Baux score (C), Revised Baux score (D), Denver score (E), SOFA Score (F), Initial 24 hour resuscitation (G), Initial 72 hour resuscitation (H), P:F nadir within the first 48 hours of injury. *p<0.05 vs Survivor, Kruskal-Wallis test.

Figure 2

Select immune mediators in the plasma of patients within 15 hours of burn and smoke inhalation injury, comparing survivors and deceased. IL-1RA (B), IL-6 (D), IL-8 (E), and MCP-1 (H) were increased in deceased patients while the ratio of IL-1β to IL-1RA was markedly decreased (*p<0.05). The concentrations of IL-1β (A), G-CSF (F), GM-CSF (G), and TNF-α (I) were statistically no different between groups. After adjusting for the effects of Age, % TBSA, and inhalation injury grade, the concentration of IL-1RA remained significantly associated with mortality (^†OR 3.12; 95% CI 1.03–9.44).