scholarly journals Autotaxin levels in serum and bronchoalveolar lavage fluid are associated with inflammatory and fibrotic biomarkers and the clinical outcome in patients with acute respiratory distress syndrome

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Lijuan Gao ◽  
Xiaoou Li ◽  
Hao Wang ◽  
Yue Liao ◽  
Yongfang Zhou ◽  
...  

Abstract Background Autotaxin (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. Methods Serum 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. Results Serum 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). Conclusion The 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.

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Asbjørn G. Petersen ◽  
Peter C. Lind ◽  
Anne-Sophie B. Jensen ◽  
Mark A. Eggertsen ◽  
Asger Granfeldt ◽  
...  

Abstract Background Senicapoc is a potent and selective blocker of KCa3.1, a calcium-activated potassium channel of intermediate conductance. In the present study, we investigated whether there is a beneficial effect of senicapoc in a large animal model of acute respiratory distress syndrome (ARDS). The primary end point was the PaO2/FiO2 ratio. Methods ARDS was induced in female pigs (42–49 kg) by repeated lung lavages followed by injurious mechanical ventilation. Animals were then randomly assigned to vehicle (n = 9) or intravenous senicapoc (10 mg, n = 9) and received lung-protective ventilation for 6 h. Results Final senicapoc plasma concentrations were 67 ± 18 nM (n = 9). Senicapoc failed to change the primary endpoint PaO2/FiO2 ratio (senicapoc, 133 ± 23 mmHg; vehicle, 149 ± 68 mmHg). Lung compliance remained similar in the two groups. Senicapoc reduced the level of white blood cells and neutrophils, while the proinflammatory cytokines TNFα, IL-1β, and IL-6 in the bronchoalveolar lavage fluid were unaltered 6 h after induction of the lung injury. Senicapoc-treatment reduced the level of neutrophils in the alveolar space but with no difference between groups in the cumulative lung injury score. Histological analysis of pulmonary hemorrhage indicated a positive effect of senicapoc on alveolar–capillary barrier function, but this was not supported by measurements of albumin content and total protein in the bronchoalveolar lavage fluid. Conclusions In summary, senicapoc failed to improve the primary endpoint PaO2/FiO2 ratio, but reduced pulmonary hemorrhage and the influx of neutrophils into the lung. These findings open the perspective that blocking KCa3.1 channels is a potential treatment to reduce alveolar neutrophil accumulation and improve long-term outcome in ARDS.


Author(s):  
Reza Jahromi ◽  
Arezoo Avazpour ◽  
Maryam Jahromi ◽  
Jalile Alavi

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly affects the respiratory system with some patients rapidly progressing to acute respiratory distress syndrome (ARDS). The most common symptoms of the patients are fever, cough, dyspnea, myalgia, and fatigue. Nasopharyngeal and oropharyngeal swab specimens tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) are the most commonly used methods to diagnose COVID-19. Herein, we investigate and discuss a young case of COVID-19, without any pre-existing medical conditions, whose both nasopharyngeal and oropharyngeal swab tests of SARS-CoV-2 were negative in the prodromal phase. However, after three days, with severe dyspnea and rapidly progressed acute respiratory distress syndrome (ARDS), the case was identified as infected by COVID-19 by testing bronchoalveolar lavage fluid (BALF). The patient was intubated in the intensive care unit (ICU) but expired on the fourth day. This case shows the importance of active and accurate monitoring of the patients showing COVID-19 symptoms. Although the BALF test has a higher exposure risk, it is considered more accurate and recommended if performed by an expert operator.


Sign in / Sign up

Export Citation Format

Share Document