scholarly journals Identification of RPSA as a Potential Biomarker in Bronchoalveolar Lavage Fluid for Acute Respiratory Distress Syndrome

Author(s):  
Yang Xia ◽  
Lei Gao ◽  
Lili Guo ◽  
Hao Li ◽  
Min Shao ◽  
...  

Abstract BackgroundAcute respiratory distress syndrome (ARDS) is a life-threatening condition leading to severe pulmonary injuries, and proteomic analysis of bronchoalveolar lavage fluid (BALF) might elucidate potential biomarkers for diagnosis and targets for treatment of ARDS. MethodsThrough iTRAQ analysis, we investigated paired BALF samples from three ARDS patients in the acute and recovery phases. The proteins sharing the same expression patterns between the two ARDS phases among different patients were determined as co-upregulated and co-downregulated proteins (CUDPs), and differentially expressed proteins (DEPs), whose fold change > 1.2 and P value < 0.05, were selected from CUDPs. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to determine the enriched functions and pathways of the CUDPs. Protein-protein interaction (PPI) network was generated at STRING database, and hub genes were identified by the Cytoscape software. A549 cells were treated by lipopolysaccharide (LPS) to simulate alveolar epithelial cells in ARDS.ResultsWe identified 374 CUDPs and 53 DEPs. The GO analysis indicated that the most significantly enriched function was neutrophil mediated immunity response, and the KEGG analysis revealed that the 374 CUDPs were most significantly enriched in Coronavirus disease COVID-19 interaction. RPSA was discovered as the most top hub gene among DEPs, and was downregulated at protein levels during ARDS recovery. Moreover, we further confirmed that both RNA and protein level of RPSA increased upon inflammatory stimulation in vitro.ConclusionOur results proposed RPSA as a candidate for biomarker and therapeutic target 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.


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