Abstract
BackgroundAutotaxin (ATX) is a secreted glycoprotein that is widely present in extracellular biological fluids and has been implicated in many inflammatory and fibrotic diseases. However, the clinical impact of the release of ATX in patients with acute respiratory distress syndrome (ARDS) remains unclear.MethodsSerum and bronchoalveolar lavage fluid (BALF) levels of ATX, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-7, fibronectin, oncostatin M (OSM), and SPARC (secreted protein acidic and rich in cysteine) were collected from 52 patients with ARDS within 24 h of diagnosis. All cytokines were measured by Magnetic Luminex Assay. BALF albumin (BA) and serum albumin (SA) were measured by enzyme-linked immunosorbent assay.ResultsSerum ATX, MMP-7, and BALF IL-8 levels were significantly higher in patients who did not survive than in those who survived up to 28 days after diagnosis of ARDS (P < 0.05). BALF and serum ATX levels were correlated with IL-6, IL-8, and MMP-7 levels in BALF and serum, respectively. In addition, BALF ATX was positively correlated with BALF TNF-α, fibronectin, OSM, and SPARC as well as the BA/SA ratio, while serum ATX was correlated with severity of illness based on the SOFA score and PaO2/FIO2 ratio. Furthermore, serum ATX was better able to predict 28-day ARDS-related mortality (area under the curve 0.744, P < 0.01) than the SOFA score, APACHE II score, or PaO2/FIO2 ratio. Serum ATX independently predicted mortality in a univariate Cox regression model (P < 0.0001).ConclusionThe serum ATX level is a potential prognostic biomarker in patients with ARDS. BALF ATX is associated with pulmonary biomarkers of inflammation and fibrosis, suggesting a role of ATX in the pathogenesis of ARDS.
Highlights
Autotaxin (ATX) is a secreted glycoprotein that is widely present in extracellular biological fluids and has been implicated in many inflammatory and fibrotic diseases
We demonstrated that serum ATX levels were independently associated with the Sequential Organ Failure Assessment (SOFA) score and Arterial oxygen tension (PaO2)/Fraction of inspired oxygen (FIO2) ratio, which are widely used indicators of acute respiratory distress syndrome (ARDS) severity, and that there was a relationship between an elevated serum ATX level and a higher risk of mortality in patients with ARDS
We found that ATX levels were associated with biomarkers of inflammation and fibrosis, including IL-6, IL-8, tumor necrosis factor (TNF)-α, Matrix metalloproteinase7 (MMP-7), oncostatin M (OSM), Secreted protein acidic and rich in cysteine (SPARC), and fibronectin
Summary
Autotaxin (ATX) is a secreted glycoprotein that is widely present in extracellular biological fluids and has been implicated in many inflammatory and fibrotic diseases. The clinical impact of the release of ATX in patients with acute respiratory distress syndrome (ARDS) remains unclear. Acute respiratory distress syndrome (ARDS) is a common and fatal complication of critical illness and is characterized by diffuse interstitial inflammation, noncardiogenic pulmonary edema, and arterial hypoxemia [1, 2]. Despite decades of research effort, the mortality rate remains high in the range of 35–46% [3], in patients who present with a fibroproliferative lung response [4]. An increasing body of research has demonstrated robust collagen synthesis in the lungs of patients with ARDS as early as 24 h after onset of the illness [5, 6]. Histological assessment of the lungs in patients with ARDS has clearly demonstrated that fibroproliferation is present early in a substantial proportion of patients [7]. Understanding early signals that predict the long-term outcome in patients with ARDS may prove beneficial for predicting the need for more aggressive treatment and to identify novel therapeutic strategies
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