Inhalation Injury Severity and Systemic Immune Perturbations in Burned Adults

Abstract

Objective We aimed to determine if 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. Summary Background Data Previously we reported that the pulmonary inflammatory response is enhanced with worse grades of inhalation injury, and that those who die from their injuries have a blunted pulmonary immune profile compared to 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 one of five 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 ELISA. Results The concentrations of several plasma immune mediators were increased with worse inhalation injury severity, even after adjusting for age and % TBSA. 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 (MCP)-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 MCP-1 were higher in deceased patients compared to survivors (p<0.05 for all), while IL-4 and IL-7 were lower (p<0.05). After adjusting for the effects of age, % TBSA, and inhalation injury grade, plasma IL-1RA remained significantly associated with mortality (OR 3.12, 95% CI 1.03–9.44). Plasma IL-1RA also correlated with % TBSA, inhalation injury grade, fluid resuscitation, Baux score, revised Baux score, Denver score, and the Sequential Organ Failure Assessment score. Conclusion The severity of smoke inhalation injury has systemically reaching effects, which argues in favor of treating inhalation injury in a graded manner. Additionally, several plasma immune mediators measured early after injury were associated with mortality. Of these, IL-1RA appeared to have the strongest correlation with injury severity and outcomes measures, which may explain the blunted pulmonary immune response we previously found in non-survivors.

Alteration of Leukocyte Count Correlates With Increased Pulmonary Vascular Permeability and Decreased PaO2

“…Davis and colleagues also investigated the role of inhalation injury on systemic levels of different cytokines and its impact on mortality after burns [35]. Their findings support that the inhalation injury affects both mortality and the systemic inflammation in a graded manner.…”

Intraalveolar TNF-α in Combined Burn and Inhalation Injury Compared With Intraalveolar Interleukin-6

“…Many studies have demonstrated an increase in the intraalveolar pulmonary expression of TNF-α after ventilator therapy alone in vitro 20,21 and in vivo 22,23 ; this phenomenon is proposed to contribute to ventilator induced lung injury. 24 To avoid this effect in our small animal model, we used volume controlled low pressure ventilation (Table 1), which has been proven to be less harmful to the lung than other forms of mechanical ventilation.…”

Mécanismes de toxicité des fumées d’incendie (monoxyde de carbone et cyanures exclus)

“…À l'inverse, chez les patients brûlés ayant inhalé des gaz toxiques, la fibroscopie peut faciliter l'intubation en pré-sence de lésions des voies aériennes supérieures, permettre une toilette bronchique en éliminant les débris muqueux et les sécrétions riches en suie difficiles à mobiliser et prédire le risque de décès des suites d'un SDRA [17,18]. Le profil proinflammatoire des cytokines mesurées dans le plasma ou le liquide de lavage bronchoalvéolaire de ces patients reflète la gravité des lésions bronchopulmonaires d'inhalation et est étroitement corrélé au pronostic final [18,19]. Néanmoins, une franche hyporéponse immune initiale à l'agression thermique semble associée à une évolution fatale [20].…”