Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of Lung Inflammation

摘要

The role of lung inflammatory mediators in the development of lung injury following smoke inhalation is unknown. Our objectives are to determine whether initial markers of inflammation or longitudinal changes in inflammatory markers are associated with ARDS or hypoxemia. Study design: Bronchial secretions from 200-250 intubated patients with smoke inhalation injury will be evaluated for initial and longitudinal changes concentrations of substance P, TNF- , IL-1, IL-8, and IL-10, as well as cell count and differential every two hours to a maximum of 72 hours. Initial lung inflammation and changes in inflammatory markers will be compared in patients with and without subsequent significant lung injury. We have enrolled 123 subjects. To date, we have completed sample assays and data analysis on a subset of 21 subjects with early samples. We have assessed longitudinal changes in TNF- , IL-1 , IL-8, IL-10, sFASl, substance P, IL-1RA, 2M, MMP-9, and TIMP-1 concentrations over the first 36 hours post-exposure, and looked at the relation between these biomarkers and hypoxemia and ARDS. We have defined temporal changes in IL-8, IL-1 , IL-1RA/IL- 1 , and TNF- /TNF-R2 post-exposure, and have found that initial concentrations of IL-8 and the ratio of 2-M to IL-8 are significant predictors of subsequent hypoxemia. Further analysis of additional markers, including neutrophils, proteases, and protease-inhibitors, have been started.