Acute Respiratory Distress Syndrome Group Research Articles

Clinical Value and Mechanism of Long Non-Coding RNA UCA1 in Acute Respiratory Distress Syndrome Induced by Cardiopulmonary Bypass.

Long non-coding RNA (lncRNA) can be used as a biological marker for the diagnosis and treatment of various diseases. The study aimed to detect changes in the expression of lncRNA for urothelial carcinoma associated 1 (UCA1) in patients with cardiopulmonary bypass (CPB)-induced acute respiratory distress syndrome (ARDS). Clinical values and cell function in ARDS were explored. In total, 195 patients without CPB-induced ARDS were included in the control group, and 85 patients with ARDS were included in the ARDS group. Serum UCA1 levels were measured by quantitative real-time polymerase chain reaction. A549 was used for the cell experiments by establishing oxygen-glucose deprivation/reperfusion (OGD/R) cell models, and the cell viability and apoptosis were tested. The concentration of inflammatory factors was tested by an enzyme-linked immunosorbent assay. A luciferase reporting assay was applied for target gene analysis. Quantitative real-time polymerase chain reaction revealed a gradual increase in serum UCA1 in both control and ARDS cases, and patients with ARDS had higher levels of UCA1 than those in the control group. Serum UCA1 was positively correlated with serum tumour necrosis factor-α and interleukin-6 concentration in patients with ARDS. UCA1 had the ability to distinguish patients with ARDS fromthose without it. UCA1 inhibition protected against lung injury and inhibited cell inflammation invitro. MicroRNA (miR-182-5p) was downregulated in OGD/R-induced cell models and sponged by UCA1. Elevated expression of UCA1 may be associated with the occurrence of ARDS after CPB surgery. The regulatory role of UCA1 in ARDS might be related to inflammation and downregulated miR-182-5p in alveolar epithelial cells.

Identification of Genes as Potential Biomarkers for Sepsis-related ARDS using Weighted Gene Co-expression Network Analysis.

Acute respiratory distress syndrome (ARDS) caused by sepsis presents a high mortality rate; therefore, identification of susceptibility genes of sepsis to ARDS at an early stage is particularly critical. The GSE66890 dataset was downloaded and analyzed by WGCNA to obtain modules. Then, GO and KEGG analyses of the module genes were performed. Then, the PPI network and LASSO model were constructed to identify the key genes. Finally, expression levels of the screened genes were validated in clinical subjects. We obtained 17 genes merged modules via WGCNA, and the dark module and tan module were the most positively and negatively correlated with sepsis-induced ARDS, respectively. Based on gene intersections of the module genes, 11 hub genes were identified in the dark module, and 5 hub genes were identified in the tan module. Finally, the six key genes were identified by constructing the LASSO model. We further detected the screened genes expression in clinical samples, and as the bioinformatics analysis revealed, the expressions of NANOG, RAC1, TWIST1, and SNW1 were significantly upregulated in the ARDS group compared to the sepsis group, and IMP3 and TUBB4B were significantly downregulated. We identified six genes as the potential biomarkers in sepsis-related ARDS. Our findings may enhance the knowledge of the molecular mechanisms behind the development of sepsisinduced ARDS.

Value of plasma AGEs and sRAGE expression in predicting the occurrence of ARDS in elderly COPD patients.

This study aimed to explore the diagnostic value of advanced glycation end products (AGEs) and soluble receptors for advanced glycation end products (sRAGE) by detecting the expression levels of AGEs and sRAGE in the plasma of elderly patients with chronic obstructive pulmonary disease (COPD) combined with acute respiratory distress syndrome (ARDS). For this purpose, 110 COPD patients were divided into the elderly COPD group (n=95) and the elderly COPD combined with the ARDS group (n=15). An additional 100 healthy people were recruited as the control group. All patients were assessed with Acute Physiology and Chronic Health Evaluation (APACHE II score) after admission. The levels of AGEs and sRAGE in the plasma were measured by enzyme-linked immunosorbent assay. Results showed that compared with the elderly COPD group, the APACHE II score was significantly higher in the elderly COPD combined with ARDS group (P < 0.05); the level of plasma AGEs in the control group, the elderly COPD group, and the elderly COPD combined with ARDS group decreased in turn (P < 0.05), and the level of sRAGE increased in turn (P < 0.05). Pearson analysis exhibited that the plasma AGEs level was negatively correlated with the APACHE II score (r = -0.681, P < 0.05), and plasma sRAGE level was positively correlated with the APACHE II score (r = 0.653, P < 0.05). Binary Logistic analysis demonstrated that AGEs were the protective factor for ARDS in elderly COPD patients (P < 0.05), and sRAGE was the risk factor for ARDS in elderly COPD patients (P < 0.05). The areas under the curve of plasma AGEs, sRAGE, and their combination in the prediction of ARDS in elderly COPD patients were 0.860 (95%CI: 0.785-0.935), 0.756 (95%CI: 0.659-0.853), and 0.882 (95%CI: 0.813-0.951), respectively. The decreased level of AGEs and the increased level of sRAGE in the plasma of COPD patients with ARDS are associated with the disease severity and have a certain diagnostic value for ARDS in COPD patients, which may be potential markers for the clinical diagnosis of COPD combined with ARDS.

Same but Different-ECMO in COVID-19 and ARDS of Other Etiologies. Comparison of Survival Outcomes and Management in Different ARDS Groups.

Background: COVID-19 has led to increased numbers of patients in need of venovenous extracorporeal membrane oxygenation (ECMO) support, but knowledge on management in comparison to acute respiratory distress syndrome (ARDS) of other etiologies is still lacking. We analyzed venovenous ECMO management and survival outcomes in patients with COVID-19 in comparison to influenza ARDS and pulmonary ARDS of other origin. Results: Retrospective analysis of prospective venovenous ECMO registry-based data collection was performed. One hundred consecutive venovenous ECMO patients with severe ARDS were included (41 COVID-19, 24 influenza A, 35 ARDS of other etiologies). Patients with COVID-19 had higher BMI (body mass index), lower SOFA (Sequential Organ Failure Assessment) and APACHE II (Acute Physiology and Chronic Health Evaluation II) scores, lower C-reactive protein and procalcitonin levels and less vasoactive support at ECMO initiation. Significantly more patients were mechanically ventilated for more than 7 days prior to ECMO initiation in the COVID-19 group, however they were ventilated with lower tidal volumes and more often received additional rescue therapies prior to and on ECMO. COVID-19 patients had significantly more barotrauma and thrombotic events on ECMO. There were no differences in weaning of ECMO, however duration of ECMO runs and ICU length of stay was significantly longer in the COVID-19 group. The leading cause of death in the COVID-19 group was irreversible respiratory failure, while uncontrolled sepsis and multiorgan failure were leading causes in the other 2 groups. All patients who survived ICU treatment were discharged out of hospital, and there were no differences in survival among groups at 180 days. Conclusions: Survival outcomes of venovenous ECMO patients do not differ between COVID-19 and ARDS of other pulmonary etiologies. ARDS guidelines were in greater proportion adhered to in COVID-19 patients, with, however, longer time to ECMO initiation. COVID-19 ARDS seems specific as a more single-organ disease with longer ECMO duration and irreversible respiratory failure as a main cause of ICU mortality.

Hispidulin exerts a protective effect against oleic acid induced-ARDS in the rat via inhibition of ACE activity and MAPK pathway

ABSTRACT This study investigates the protective role of Hispidulin on acute respiratory distress syndrome (ARDS) in rats. Rats were divided into three groups: control, ARDS, ARDS+ Hispidulin. The ARDS models were established by injecting rats with oleic acid. Hispidulin (100 mg/kg) was injected i.p. an hour before ARDS. Myeloperoxidase (MPO), Interleukin-8 (IL-8), Mitogen-activated protein kinases (MAPK), Lipid Peroxidation (LPO), Superoxide Dismutase (SOD), Glutathione (GSH), and Angiotensin-converting enzyme (ACE) were determined by ELISA. Tumor necrosis factor-alpha (TNF-α) expression was described by RT-qPCR. Caspase-3 immunostaining was performed to evaluate apoptosis. Compared with the model group, a significant decrease was observed in the MPO, IL-8, MAPK, ACE, LPO levels, and TNF-α expression in the ARDS+ Hispidulin group. Moreover, reduced caspase-3 immunoreactivity and activity of ACE were detected in the Hispidulin+ARDS group. The protective effect of Hispidulin treatment may act through inhibition of the ACE activity and then regulation of inflammatory cytokine level and alteration of apoptosis.

Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock

BackgroundNo direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model.MethodsThirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300–400), mild-to-moderate ARDS (100–300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers.ResultsUsing CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98–1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS.ConclusionThe pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.

117: DIFFERENCES IN POST-INTENSIVE CARE SYNDROME SEQUELAE BETWEEN ARDS AND COVID ARDS SURVIVORS

Introduction: Post-intensive care syndrome (PICS) is a disorder with psychological sequalae often seen in acute respiratory distress syndrome (ARDS) survivors after intensive care unit (ICU) stays. Studies have reported post-traumatic stress disorder (PTSD) in up to 39% of ARDS survivors, and 66% have anxiety. COVID-19 respiratory failure often mirrors ARDS. We hypothesized that PICS symptoms would be worse in COVID ARDS secondary to longer ventilator hours and social isolation. Methods: The cross-sectional study enrolled survivors of ARDS and COVID ARDS admitted after 01/01/20 for a pilot study to screen for PICS. We recruited participants through Facebook ARDS survivor groups. Participants completed the Impact of Events Scale-R (PTSD), Patient Health Questionnaire-9 (PHQ-9; depression), and General Anxiety Disorder-7 (GAD-7). Independent-Samples Mann-Whitney U and Chi-Square tests were used to examine group differences. Results: We analyzed data from 16 participants (ARDS 44%; COVID ARDS 56%); median age 34.5; 63% female; 88% white, 13% Hispanic. COVID ARDS had higher median ICU days (46 vs. 10) and ventilator days (35 vs. 8) than ARDS (p=.32). Family visitation occurred in 78% of COVID vs 86% ARDS (p=.69). Clinical PTSD noted in 56% COVID ARDS compared to 29% ARDS; p=.03). Moderate depression or higher noted in 46% of survivors with no difference between groups (p=.65). Moderate anxiety or higher noted in 44% of survivors; no difference between groups (p=.20). Of those working, 38% of COVID ARDS and 14% of ARDS were unable to return to work after discharge (p=.31). Conclusions: Both groups exhibited PTSD, anxiety, and depression, impacting their ability to return to work. COVID survivors were nearly twice as likely to screen positive for clinically significant PTSD; differences in PTSD may be explained by longer ICU stays and ventilator time. Interventions to reduce PTSD and early treatment for PTSD may be needed. Group differences for ICU days and ventilator days were clinically significant; statistical significance likely impacted by sample size. COVID ARDS survivors were less likely to have visitors, which may have contributed to PICS sequelae. It is unclear if personal protective equipment and strict isolation may have impacted visitation and contributed to higher PTSD in the COVID ARDS group.

Effects of airway pressure release ventilation on multi-organ injuries in severe acute respiratory distress syndrome pig models

BackgroundExtra-pulmonary multi-organ failure in patients with severe acute respiratory distress syndrome (ARDS) is a major cause of high mortality. Our purpose is to assess whether airway pressure release ventilation (APRV) causes more multi-organ damage than low tidal volume ventilation (LTV).MethodsTwenty one pigs were randomized into control group (n = 3), ARDS group (n = 3), LTV group (n = 8) and APRV group (n = 7). Severe ARDS model was induced by repeated bronchial saline lavages. Pigs were ventilated and monitored continuously for 48 h. Respiratory data, hemodynamic data, serum inflammatory cytokines were collected throughout the study. Histological injury and apoptosis were assessed by two pathologists.ResultsAfter severe ARDS modeling, pigs in ARDS, LTV and APRV groups experienced significant hypoxemia and reduced lung static compliance (Cstat). Oxygenation recovered progressively after 16 h mechanical ventilation (MV) in LTV and APRV group. The results of the repeated measures ANOVA showed no statistical difference in the PaO2/FiO2 ratio between the APRV and LTV groups (p = 0.54). The Cstat showed a considerable improvement in APRV group with statistical significance (p < 0.01), which was significantly higher than in the LTV group since 16 h (p = 0.04). Histological injury scores showed a significantly lower injury score in the middle and lower lobes of the right lung in the APRV group compared to LTV (pmiddle = 0.04, plower = 0.01), and no significant increase in injury scores for extra-pulmonary organs, including kidney (p = 0.10), small intestine (p = 1.0), liver (p = 0.14, p = 0.13) and heart (p = 0.20). There were no significant differences in serum inflammatory cytokines between the two groups.ConclusionIn conclusion, in the experimental pig models of severe ARDS induced by repetitive saline lavage, APRV improved lung compliance with reduced lung injury of middle and lower lobes, and did not demonstrate more extra-pulmonary organ injuries as compared with LTV.

Excessive Sedation as a Risk Factor for Delirium: A Comparison between Two Cohorts of ARDS Critically Ill Patients with and without COVID-19.

Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedation-in terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortality-between COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p &lt; 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p &lt; 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16-27) vs. 14 (10.5-19.5) days (p &lt; 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.

Comparison of Clinical Characteristics and Predictors of Mortality between Direct and Indirect ARDS.

Background and Objectives: Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous syndrome that encompasses lung injury from a direct pulmonary or indirect systemic insult. Studies have shown that direct and indirect ARDS differ in their pathophysiologic process. In this study, we aimed to compare the different clinical characteristics and predictors of 28-day mortality between direct and indirect ARDS. Materials and Methods: The data of 1291 ARDS patients from September 2012 to December 2021 at the Second Affiliated Hospital of Chongqing Medical University were reviewed. We enrolled 451 ARDS patients in our study through inclusion and exclusion criteria. According to the risk factors, each patient was divided into direct (n = 239) or indirect (n = 212) ARDS groups. The primary outcome was 28-day mortality. Results: The patients with direct ARDS were more likely to be older (p &lt; 0.001) and male (p = 0.009) and have more comorbidity (p &lt; 0.05) and higher 28-day mortality (p &lt; 0.001) than those with indirect ARDS. Age and multiple organ dysfunction syndrome (MODS) were predictors of 28-day mortality in the direct ARDS group, while age, MODS, creatinine, prothrombin time (PT), and oxygenation index (OI) were independent predictors of 28-day mortality in the indirect ARDS group. Creatinine, PT, and OI have interactions with ARDS types (all p &lt; 0.01). Conclusions: The patients with direct ARDS were more likely to be older and male and have worse conditions and prognoses than those with indirect ARDS. Creatinine, PT, and OI were predictors of 28-day mortality only in the indirect ARDS group. The differences between direct and indirect ARDS suggest the need for different management strategies of ARDS.

PRONE POSITIONING IN COVID-19 VS NON-COVID-19 ARDS IN THE EARLY COVID-19 PANDEMIC

PRONE POSITIONING IN COVID-19 VS NON-COVID-19 ARDS IN THE EARLY COVID-19 PANDEMIC

Establishment and verification of LIPS score combined with APACHE II score and oxygenation index to predict the occurrence model of ARDS

To construct and verify the occurrence model of acute respiratory distress syndrome (ARDS) using lung injury prediction score (LIPS) combined with acute physiology and chronic health evaluation II (APACHE II) score and oxygenation index (PaO2/FiO2). Using a prospective cohort study method, 244 patients with complete medical records who were admitted to the intensive care unit (ICU) of Peking University Third Hospital from December 2020 to July 2022 were selected as research objects according to the inclusion and exclusion criteria. They were divided into training set (173 cases) and validation set (71 cases). Patients' gender, age, body mass index (BMI), various causes (shock, sepsis, craniocerebral injury, pulmonary contusion, multiple trauma, aspiration, pneumonia, acute abdomen, hypoproteinemia, acidosis, major surgery, etc.), underlying diseases (diabetes, malignant tumor, cerebrovascular disease, liver disease, kidney disease) and laboratory test indicators were collected. According to the above data, the LIPS score, APACHE II score, sequential organ failure assessment (SOFA) and PaO2/FiO2, etc within 24 hours after admission to the ICU were calculated. Univariate analysis was used to screen the influencing factors for the occurrence of ARDS, and the factors with P < 0.2 were included in the multivariate Logistic regression analysis to screen out the independent predictive factors for the occurrence of ARDS. According to the results of multivariate Logistic regression analysis, the risk score of patients with ARDS was obtained to construct the risk prediction model of ARDS, the receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated. The established ARDS prediction model was externally validated, and ROC curves were drawn to evaluate the predictive accuracy of the prediction model for the occurrence of ARDS in critically ill patients, and the AUC of the validation set was calculated to analyze the predictive performance of each risk factor on the occurrence of ARDS. A total of 173 patients were enrolled in the training set, including 121 patients without ARDS and 52 patients with ARDS; 77 cases of acute abdomen, 64 cases of sepsis, 60 cases of shock, 51 cases of acidosis, 40 cases of hypoproteinemia, 37 cases of diabetes, 34 cases of craniocerebral injury, 34 cases of abnormal liver function, 28 cases of multiple trauma, 23 cases of malignant tumor, 23 cases of spinal orthopedic surgery, 17 cases of obesity, 12 cases of pneumonia, 11 cases of pulmonary contusion, and 7 cases of chronic kidney disease, chemotherapy in 6 cases, and aspiration in 2 cases. The rates of shock, sepsis, acute abdomen, acidosis, abnormal liver function, lung contusion, pneumonia and aspiration, gender, age, LIPS score, APACHE II score, and SOFA score in the ARDS group were significantly higher than those in the non-ARDS group (all P < 0.05), moreover, PaO2/FiO2 ratio was significantly lower than that of non-ARDS group (P < 0.01). Multivariate Logistic regression analysis showed that LIPS score, APACHE II score, and PaO2/FiO2 ratio were independent risk factors for ARDS in ICU patients with high risk factors for ARDS, and the odds ratio (OR) was 1.768 [95% confidence interval (95%CI) was 1.380-2.266], 1.242 (95%CI was 1.089-1.417), 0.985 (95%CI was 0.978-0.991), all P < 0.05. ROC curve analysis showed that the AUC of the ARDS prediction model training set was 0.920, the sensitivity was 86.5%, and the specificity was 86.8%; the AUC of the verification set was 0.896, the sensitivity was 96.8%, and the specificity was 76.6%. LIPS score, APACHE II score and PaO2/FiO2 are independent risk factors for the occurrence of ARDS in ICU patients with high risk factors for ARDS. The ARDS risk prediction model established based on these three indicators has a good predictive ability for the occurrence of ARDS in critically ill patients, wihich needs to be verified by multicenter cohort studies.

Identification and validation of autophagy-related genes in exogenous sepsis-induced acute respiratory distress syndrome.

ObjectiveTo analyze the differential expression of autophagy‐related genes of sepsis‐induced acute respiratory distress syndrome (ARDS) as potential markers for early diagnosis.MethodsMale Sprague–Dawley rats (aged 8 weeks) were selected and randomly divided into sepsis‐induced ARDS group (n = 6) and a normal control group (n = 6). Lung tissue samples were collected for high‐throughput sequencing using Illumina HiSeq sequencing platform in the paired‐end sequencing mode. Differentially expressed genes (DEGs) were screened by DESeq. 2 software [|log2FC | ≥1 and p < .05] and autophagy‐related genes were identified using Mouse Genome Informatics. Co‐expressed autophagy‐related DEGs from these two datasets were filtered by construction of a Venn diagram. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these autophagy‐related DEGs and a protein interaction network was constructed using STRING and Cytoscape software to identify hub genes, which were verified by real‐time quantitative polymerase chain reaction (qRT‐PCR).ResultsA total of 42 autophagy‐related DEGs (26 upregulated genes and 16 downregulated genes) were identified. The GO and KEGG pathway analyses showed enrichment in 969 biological processes (BPs), three cellular components (CCs), eight molecular functions (MFs) and 27 signaling pathways. The protein interaction (PPI) network revealed 42 node proteins and 75 interacting edges, with an average node degree of 3.52, and an average local clustering coefficient of 0.509. Among the top 10 hub genes with the RNA‐Seq, six hub genes (Stat3, Il10, Ifng, Hmox1, Hif1a, and Nod2) were validated by qRT‐PCR (all p < .05).Conclusion42 potential autophagy‐related genes associated with sepsis‐induced ARDS lung injury were identified and six hub genes (Stat3, Il10, Ifng, Hmox1, Hif1a, and Nod2) may affect the development of ARDS by regulating autophagy. These results expanded our understanding of ARDS and might be useful in treatment of exogenous sepsis‐induced ARDS.

Angiopoietin-Like Protein 2 Is Increased in Obese Mouse Models of Lung Injury.

Objective To investigate the regulatory role of angiopoietin-1ike protein 2 (Angptl 2) in the pathogenesis of acute respiratory distress syndrome (ARDS). Methods A high-fat diet (HFD) and tail vein injection of 0.1 ml/kg oleic acid were used to induce acute lung injury (ALI) and ARDS models, and male Kunming mice were randomly divided into four groups: control group (injected with normal saline), ALI group (injected with oleic acid), HFD group (injection of normal saline), and ARDS group (HFD+injection of oleic acid). The degree of lung injury was assessed by lung histopathology score and lung injury index. At the same time, the mRNA and protein expression levels of Angptl 2 in lung tissue were also detected to determine the relationship between Angptl 2 and ARDS. Results Lee's index of the HFD group and ARDS group was significantly higher than that of the control group and ALI group (P < 0.05), and the lung injury index of the ARDS group was significantly higher than that of the ALI group. The expression of Angptl 2 in the lung tissue of the ALI group and ARDS group was significantly different, and the Angptl 2 mRNA level was the highest in the ARDS group. Immunohistochemistry showed that the alveolar walls of the ALI group and ARDS group were severely collapsed, and the ARDS group had the greatest Angptl 2 aggregation at the site of edema exudation. Conclusion Collectively, obesity might be mediated by Angptl 2 and promotes lung injury. Immunohistochemistry analysis showed that the expression of the receptor on alveolar walls was correlated with Angptl 2, which increased alveolar wall permeability, edema fluid exudation, and alveolar wall collapse. Thus, Angptl 2 might be a target for improving the treatment of ARDS.

Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.

Acute respiratory distress syndrome (ARDS), a life-threatening condition characterized by hypoxemia and poor lung compliance, is associated with high mortality. ARDS induced by COVID-19 has similar clinical presentations and pathological manifestations as non-COVID-19 ARDS. However, COVID-19 ARDS is associated with a more protracted inflammatory respiratory failure compared to traditional ARDS. Therefore, a comprehensive molecular comparison of ARDS of different etiologies groups may pave the way for more specific clinical interventions. In this study, we compared COVID-19 ARDS (n = 43) and bacterial sepsis-induced (non-COVID-19) ARDS (n = 24) using multi-omic plasma profiles covering 663 metabolites, 1,051 lipids, and 266 proteins. To address both between- and within- ARDS group variabilities we followed two approaches. First, we identified 706 molecules differently abundant between the two ARDS etiologies, revealing more than 40 biological processes differently regulated between the two groups. From these processes, we assembled a cascade of therapeutically relevant pathways downstream of sphingosine metabolism. The analysis suggests a possible overactivation of arginine metabolism involved in long-term sequelae of ARDS and highlights the potential of JAK inhibitors to improve outcomes in bacterial sepsis-induced ARDS. The second part of our study involved the comparison of the two ARDS groups with respect to clinical manifestations. Using a data-driven multi-omic network, we identified signatures of acute kidney injury (AKI) and thrombocytosis within each ARDS group. The AKI-associated network implicated mitochondrial dysregulation which might lead to post-ARDS renal-sequalae. The thrombocytosis-associated network hinted at a synergy between prothrombotic processes, namely IL-17, MAPK, TNF signaling pathways, and cell adhesion molecules. Thus, we speculate that combination therapy targeting two or more of these processes may ameliorate thrombocytosis-mediated hypercoagulation. We present a first comprehensive molecular characterization of differences between two ARDS etiologies-COVID-19 and bacterial sepsis. Further investigation into the identified pathways will lead to a better understanding of the pathophysiological processes, potentially enabling novel therapeutic interventions.

D-tagatose protects against oleic acid-induced acute respiratory distress syndrome in rats by activating PTEN/PI3K/AKT pathway.

Acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar–capillary barrier, resulting in severe alveolar edema and inflammation. D-tagatose (TAG) is a low-calorie fructose isomer with diverse biological activities whose role in ARDS has never been explored. We found that TAG protects lung tissues from injury in the oleic acid-induced rat model of ARDS. Seventeen male Sprague–Dawley rats were randomly assigned to 3 groups: Sham (n = 5), ARDS (n = 6), and TAG + ARDS (n = 6). The treatment groups were injected with oleic acid to induce ARDS, and the TAG + ARDS group was given TAG 3 days before the induction. After the treatments, the effect of TAG was evaluated by blood gas analysis and observing the gross and histological structure of the lung. The results showed that TAG significantly improved the oxygenation function, reduced the respiratory acidosis and the inflammatory response. TAG also improved the vascular permeability in ARDS rats and promoted the differentiation of alveolar type II cells, maintaining the stability of the alveolar structure. This protective effect of TAG on the lung may be achieved by activating the PTEN/PI3K/AKT pathway. Thus, TAG protects against oleic acid-induced ARDS in rats, suggesting a new clinical strategy for treating the condition.

Effect of prone positioning on gas exchange according to lung morphology in patients with acute respiratory distress syndrome.

BackgroundThere are limited data on the clinical effects of prone positioning according to lung morphology. We aimed to determine whether the gas exchange response to prone positioning differs according to lung morphology.MethodsThis retrospective study included adult patients with moderate-to-severe acute respiratory distress syndrome (ARDS). The lung morphology of ARDS was assessed by chest computed tomography scan and classified as “diffuse” or “focal.” The primary outcome was change in partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio after the first prone positioning session: first, using the entire cohort, and second, using subgroups of patients with diffuse ARDS matched 2 to 1 with patients with focal ARDS at baseline.ResultsNinety-five patients were included (focal ARDS group, 23; diffuse ARDS group, 72). Before prone positioning, the focal ARDS group showed worse oxygenation than the diffuse ARDS group (median PaO2/FiO2 ratio, 79.9 mm Hg [interquartile range (IQR)], 67.7–112.6 vs. 104.0 mm Hg [IQR, 77.6–135.7]; P=0.042). During prone positioning, the focal ARDS group showed a greater improvement in the PaO2/FiO2 ratio than the diffuse ARDS group (median, 55.8 mm Hg [IQR, 11.1–109.2] vs. 42.8 mm Hg [IQR, 11.6–83.2]); however, the difference was not significant (P=0.705). Among the PaO2/FiO2-matched cohort, there was no significant difference in change in PaO2/FiO2 ratio after prone positioning between the groups (P=0.904).ConclusionsIn patients with moderate-to-severe ARDS, changes in PaO2/FiO2 ratio after prone positioning did not differ according to lung morphology. Therefore, prone positioning can be considered as soon as indicated, regardless of ARDS lung morphology.

The protective effect of xanthenone against LPS-induced COVID-19 acute respiratory distress syndrome (ARDS) by modulating the ACE2/Ang-1-7 signaling pathway.

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IDENTIFICATION OF RISK FACTORS PREDICTING MORTALITY IN PATIENTS WITH ARDS RELATED TO SEVERE COVID-19

TYPE: Late Breaking Abstract TOPIC: Chest Infections PURPOSE: Acute respiratory distress syndrome (ARDS) is one of the common clinical manifestations of severe COVID19 and it is also responsible for the high ventilators demand in worldwide.The aim of our study was to assess the risk factors predicting mortality in patients with ARDS developing as complication of severe COVID19 and use appropriate treatment approaches for improving clinical outcomes in such patients. METHODS: Our study was retrospective and we collected clinical data of 289 patients with severe COVID19 complicated with ARDS from five COVID19 hospitals ,from 01 August 2021 to 30 December 2021.The clinical characteristics of the survivors ARDS group(168[58.1%])and non-survivors ARDS group(121[41.9%]) of COVID19 patients were clinically,laboratory ,and radiographically compared. RESULTS: Median age of non-survivors with ARDS was older than those with survivors with ARDS(p<0.001),male and BMI >30 were more likely to die.The incidence of consolidation/ground glass opacities ratio (C/GGO) >1 in lung parenchyma,secondary bacterial infection,mechanical ventilation and lack of use dexamethasone before intubation were common findings among non-survivors with ARDS(p<0.002;<0.01;<0.001;and <0.003 ).High SOFA score and low Pa O2/FiO2(P/F) ratio were associated with higher mortality rate among non-survivors with ARDS . Predictors of death in patients with ARDS were:D-dimer (p<0.0004),creatinine(p<0.009),lymphocytes <0.6x109/L(p<0.001),procalcitonin(p<0.008),and BNP(p<0.0003).Among non-survivors with ARDS high PaCO2 and low arterial blood pH were common findings compared to those survive to the end of investigation(p<0.001). CONCLUSIONS: We identified predictors of mortality in patients with ARDS related to severe COVID19.Our findings may be helpful for healthcare providers take appropriate measures and impact to clinical outcomes in patients with severe COVID19 complicated with ARDS. CLINICAL IMPLICATIONS: critical care ohysicians ,nurses,pulmonologists,respiratory therapist DISCLOSURE: No significant relationships. KEYWORD: Severe COVID19.ARDS,RIsk Factors,Predicting ,Mortality

Can Alveolar-Arterial Oxygen Pressure Difference be used to Diagnose Acute Respiratory Distress Syndrome in Pneumonia Patients?

Alveolar-arterial oxygen pressure difference (P(Aa)O2) can reflect pulmonary ability to exchange oxygen; it shows good correlation with the oxygenation index (OI), which is important in diagnosing acute respiratory distress syndrome (ARDS). This study explored the ability of P(Aa)O2 in diagnosing ARDS in pneumonia patients. Methods We selected patients with community-acquired pneumonia and sepsis in the intensive care unit (ICU) of the People’s Hospital of Qiandongnan Miao and Dong Autonomous Prefecture; we measured P(Aa)O2 and the OI under anoxic conditions upon their admittance to the ICU. We divided the patients into ARDS and non-ARDS groups. We compared the differences in P(Aa)O2 and OI; we analyzed the correlation between P(Aa)O2 and ARDS. To assess the diagnostic ability of P(Aa)O2 for ARDS, we drew the receiver operating characteristic (ROC) curve. Result We found that P(Aa)O2 in the ARDS group was greater than in the non-ARDS group (t = 8.875, P &lt;0.001); the OI in the ARDS group was smaller than in the non-ARDS group (t = –6.956, P &lt;0.001). There was a positive correlation between P(Aa)O2 and ARDS (r = 0.718, P &lt;0.001). The area under the ROC curve for P(Aa)O2 in the diagnosis of ARDS was 0.931 (0.873–0.988); the cutoff value was 214.70 mmHg, the sensitivity was 89.50%, and the specificity was 85.00%. Conclusion We conclude that P(Aa)O2 is a good reference index in diagnosing ARDS