Morbidity Of Acute Respiratory Distress Syndrome Research Articles

Predicting Acute Respiratory Distress Syndrome in Severe Blunt Trauma: The Utility of Interleukin-18

Background: In trauma, direct pulmonary injury and innate immune response activation primes the lungs for acute respiratory distress syndrome (ARDS). The inflammasome-dependent release of interleukin-18 (IL-18) was recently identified as a key mediator in ARDS pathogenesis, leading us to hypothesize that plasma IL-18 is a diagnostic predictor of ARDS in severe blunt trauma. Patients and Methods: Secondary analysis of the Inflammation and Host Response to Injury database was performed on plasma cytokines collected within 12 hours of severe blunt trauma. Trauma-related cytokines, including IL-18, were compared between patients with and without ARDS and were evaluated for association with ARDS using regression analysis. Threshold cytokine concentrations predictive of ARDS were determined using receiver-operating curve (ROC) analysis. Results: Cytokine analysis of patients without ARDS patients (n = 61) compared with patients with ARDS (n = 19) demonstrated elevated plasma IL-18 concentration in ARDS and IL-18 remained correlated with ARDS on logistic regression after confounder adjustment (p = 0.008). Additionally, ROC analysis revealed IL-18 as a strong ARDS predictor (area under the curve [AUC] = 0.83), with a threshold IL-18 value of 170 pg/mL (Youden index, 0.3). Unlike in patients without ARDS, elevated IL-18 persisted in patients with ARDS during the acute injury phase (p ≤ 0.02). Other trauma-related cytokines did not correlate with ARDS. Conclusions: In severe blunt trauma, IL-18 is a robust predictor of ARDS and remains elevated throughout the acute injury phase. These findings support the use of IL-18 as a key ARDS biomarker, promoting early identification of trauma patients at greater risk of developing ARDS. Timely recognition of ARDS and implementation of advantageous supportive care practices may reduce trauma-related ARDS morbidity and costs.

Is Time the Missing Component in Protective Ventilation Strategies?*

Is Time the Missing Component in Protective Ventilation Strategies?*

Persistent inflammation and fibrosis of the lung are long-term complications of sepsis in baboons (P4015)

Abstract Sepsis-induced inflammation of the lung leads to acute respiratory distress syndrome (ARDS), which may trigger persistent fibrotic responses. We have developed a baboon model of E. coli sepsis-induced ARDS and characterized the long-term (6-24 months) effects of sepsis on the lung. By immunocytochemistry, we detected focal accumulation of neutrophils, M2 macrophages, IL17 and TGF-β positive cells, which indicates persistent inflammation in the lung, months after clinical recovery from the acute sepsis episode. Microscopical and biochemical quantification demonstrated an almost doubling of collagen content amount in the lungs of animals that survived sepsis as compared to age-matched nonexposed controls. Electron microscopy showed myofibroblast accumulation within the alveolar wall. Co-staining for fibroblast and cell proliferation markers demonstrated active cell proliferation in fibroblastic foci. Immunostaining with antibodies to procollagens showed active collagen synthesis within the fibroblastic foci and interalveolar septa. These fibroblasts were also stained with phospho Smad-2 and CTGF antibodies, suggesting that TGF-β signaling was one of the main mediators of fibrosis. In conclusion, we show that E. coli sepsis-induced ARDS triggers chronic inflammation, fibroblast proliferation and collagen deposition in the primate. These long-lasting fibrotic responses perpetuate the lung injury and may contribute to post ARDS morbidity and mortality observed in humans.

Biomarker evidence of myocardial cell injury is associated with mortality in acute respiratory distress syndrome*

Although a number of studies have reported elevated levels of markers of myocardial necrosis among critically ill patients, the association between these markers and outcome remains poorly studied in patients with lung injury. We investigated the association of elevated troponin and creatine phosphokinase isoenzyme levels with mortality and organ failure in subjects with acute respiratory distress syndrome. Retrospective study. Tertiary academic medical center. A total of 305 subjects with acute respiratory distress syndrome enrolled in a prospective intensive care unit cohort. None. Cardiac biomarker data were available on 248 of 305 patients with acute respiratory distress syndrome (81%), of which 89 patients had at least one elevated cardiac marker level (35%). The presence of an elevated cardiac marker was associated with significantly higher mortality (p = .01) and was an independent predictor of mortality (p = .02) among patients with lower severity of illness (Acute Physiology and Chronic Health Evaluation III, <79). Patients with at least one elevated cardiac marker also had significantly more organ system derangement, including noncardiovascular organ system failures (p = .02). Patients with acute respiratory distress syndrome have a high prevalence of elevated cardiac markers. The presence of elevated cardiac markers is independently associated with increased 60-day mortality and increased organ failure. This association is most pronounced among patients with lower severity of illness. These results indicate that occult myocardial injury may be an important factor in acute respiratory distress syndrome morbidity and mortality. Further study of the relevant causal relationships and mechanisms is warranted.

Initial serum ferritin levels in patients with multiple trauma and the subsequent development of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) represents a catastrophic form of inflammatory lung injury that occurs unpredictably in some, but not all, at-risk patients. In this study, we investigated serum ferritin as a marker for ARDS development in a homogenous group of patients at-risk because of multiple trauma. We hypothesized that since ferritin synthesis is increased by proinflammatory cytokines, which are increased and implicated in ARDS, that ferritin levels would increase and that ferritin increases would correlate with the degree of inflammation and therefore the development of ARDS. We studied 42 patients (25 male, 17 female) who as a consequence of multiple trauma became at-risk for developing ARDS. Using the European/American Consensus definition for ARDS, 16 (38%) patients subsequently developed ARDS (11 male and five female). We found that initial serum ferritin levels correlated with the subsequent development of both ARDS (progression to ARDS, median = 638 ng/ml; (range, 70 to 4,500) versus nonprogression to ARDS = 185 ng/ml; range, 12 to 2,850) (p = 0.02, r = -0.27) and multiple organ failure (p < 0.05, r = 0.39). Using our previously established cutoff points for serum ferritin, the positive predictive value was 62% for men and 75% for women. Initial serum ferritin levels also correlated with a measurement of the degree of initial trauma injury, i.e., the injury severity score (ISS) (p < 0.05, r = 0.37). However, there was no correlation between serum ferritin levels and other markers of clinical injury, namely, lowest PaO2/FIO2 ratio (p = 0.67), days requiring ventilation (p = 0.09), or mortality (p = 0.42). A significant association existed between serum ferritin levels and products of endothelial activation, i.e., sE-selectin (p < 0.04, r = 0.37) and sICAM-1 (p < 0.01, r = 0.21). In the future, with the development of novel anti-inflammatory therapies, early identification of specific high-risk patients would allow the institution of these therapies and thereby increase the chances of reducing ARDS morbidity and mortality.