The predictive role of serum and bronchoalveolar lavage cytokines and … (original) (raw)
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Inflammatory Cytokines in the BAL of Patients With ARDS
CHEST Journal, 1995
TN 38163. ratios were elevated for all measured cytokines, sug¬ gesting a pulmonary origin. On day 1 of ARDS, nonsurvivors had significantly higher (p=0.04) BAL: plasma ratios for TNF-a, IL-lp, IL-6, and IL-8. Over time, BAL:plasma ratios for TNF-a, IL-ip and remained elevated in nonsurvivors and decreased in survivors.
Respiratory research, 2002
The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS). We measured prospectively tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C). All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 - P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) l...
Persistent Elevation of Inflammatory Cytokines Predicts a Poor Outcome in ARDS
Chest, 1995
Background: Inflammatory cytokines have been related to the development of adult respiratory distress syndrome (ARDS), shock, and multiple organ dysfunction syndrome (MODS). We tested the hypothesis that unfavorable outcome in patients with ARDS is related to the presence of a persistent inflammatory response. For this purpose, we evaluated the behavior of inflammatory cytokines during progression of ARDS and the relationship of plasma inflammatory cytokines with clinical variables and outcome. Methods: We prospectively studied 27 consecutive patients with severe medical ARDS. Plasma levels of tumor necrosis factor alpha (TNF-a) and interleukins (ILs) 1{3, 2, 4, 6, and 8 were measured (enzyme-linked immunosorbent assay [ELISA] method) on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients were receiving mechanical ventilation. Subgroups of patients were identified based on outcome, cause of ARDS, presence or absence of sepsis, shock, and MODS at the time ARDS developed. Subgroups were compared for levels of plasma inflammatory cytokines on day 1 of ARDS and over time. Results: Of the 27 patients, 13 survived ICU admission and 14 died (a mortality rate of 52%). Overall mortality was higher in patients with sepsis (86 vs 38%, p<0.02).
Respiratory Research, 2015
Background: Acute respiratory distress syndrome (ARDS) is a disease associated with a high mortality rate. The initial phase is characterized by induction of inflammatory cytokines and chemokines and influx of circulating inflammatory cells, including macrophages which play a pivotal role in the innate and adaptive immune responses to injury. Growing evidence points to phenotypic heterogeneity and plasticity between various macrophage activation states. Methods: In this study, gene expression in alveolar macrophages and circulating leukocytes from healthy control subjects and patients with ARDS was assessed by mRNA microarray analysis. Results: Both alveolar macrophages and circulating leukocytes demonstrated up-regulation of genes encoding chemotactic factors, antimicrobial peptides, chemokine receptors, and matrix metalloproteinases. Two genes, the pro-inflammatory S100A12 and the anti-inflammatory IL-1 decoy receptor IL-1R2 were significantly induced in both cell populations in ARDS patients, which was confirmed by protein quantification. Although S100A12 levels did not correlate with disease severity, there was a significant association between early plasma levels of IL-1R2 and APACHE III scores at presentation. Moreover, higher levels of IL-1R2 in plasma were observed in non-survivors as compared to survivors at later stages of ARDS. Conclusions: These results suggest a hybrid state of alveolar macrophage activation in ARDS, with features of both alternative activation and immune tolerance/deactivation.. Furthermore, we have identified a novel plasma biomarker candidate in ARDS that correlates with the severity of systemic illness and mortality.
BMC pulmonary medicine, 2004
The predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS). We measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C). An excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and ...
Scientific Reports
Acute respiratory distress syndrome (ARDS) is associated with high mortality. We sought to identify biological pathways in ARDS that differentiate survivors from non-survivors. We studied bronchoalveolar lavage fluid (BALF) from 36 patients with ARDS (20 survivors, 16 non-survivors). Each sample, obtained within seven days of ARDS onset, was depleted of high abundance proteins and labeled for iTRAQ LC-MS/MS separately. Protein identification and relative quantification was performed employing a target-decoy strategy. A variance weighted t-test was used to identify differential expression. Ingenuity Pathway Analysis was used to determine the canonical pathways that differentiated survivors from non-survivors. We identified 1115 high confidence proteins in the BALF out of which 142 were differentially expressed between survivors and non-survivors. These proteins mapped to multiple pathways distinguishing survivors from non-survivors, including several implicated in lung injury and repair such as coagulation/thrombosis, acute phase response signaling and complement activation. We also identified proteins assigned to fibrosis and ones involved in detoxification of lipid peroxide-mediated oxidative stress to be different in survivors and non-survivors. These results support our previous findings demonstrating early differences in the BALF protein expression in ARDS survivors vs. non-survivors, including proteins that counter oxidative stress and canonical pathways associated with fibrosis. Acute respiratory distress syndrome (ARDS) occurs as a response to infectious or inflammatory triggers and is characterized by acute tachypnea, refractory hypoxia, and loss of lung compliance 1. Although a variety of conditions are triggers for ARDS, common risk factors include pneumonia (59%), extrapulmonary sepsis (16%), and aspiration (14.2%) 2. Despite widespread adoption of lung protective ventilation 3 , early use of muscle relaxants 4 , extracorporeal membrane oxygenation 5 and prone ventilation 6 , case fatality rates remain at 30-40% 2, 7-10. Regardless of the cause of ARDS, there is an unmet need to develop tools to reliably assess the mortality risk of patients early in ARDS evolution in order to design interventions to improve survival rates. The current definition of ARDS is based on physiological derangement 11 and does not identify causal mechanisms. However, there is heterogeneity in disease susceptibility 12-16 and manifestations. Only 50% of cases classified as ARDS have diffuse alveolar damage on biopsy 17. Other lung-specific responses differ with respect to the degree of hypoxia 2 , ventilator driving pressure 18 , lung stiffness 17 , and collagen deposition 19-21. A greater understanding of the differences in the