UNASSIGNED: The role of corticosteroids in acute respiratory distress syndrome (ARDS) remains contentious. This study aims to investigate the prognostic significance of immune deficiency in patients with ARDS and its response to varying doses of corticosteroids.
UNASSIGNED: This single-center, retrospective cohort study enrolled 657 ARDS patients from January 24, 2008, to September 12, 2022, at Zhongshan Hospital of Fudan University, Shanghai, China. The patients were categorized into a discovery dataset (n=357) and a validation dataset (n=300), based on admission date. Further validation of the results in the validation dataset was used to enhance the credibility of the study conclusions. The study examined the association between immune deficiency and the patients\' clinical characteristics, treatment measures, and prognosis. The primary outcome was 28-day mortality post disease onset. Data analysis was conducted from June 15, 2023 to August 15, 2023.
UNASSIGNED: The initial risk factor analysis in the discovery dataset was primarily based on the clinical characteristics, and the results suggested that immune deficiency likely impacted overall survival among patients receiving different doses of corticosteroid treatment. Multivariate analysis identified immune deficiency as an independent prognostic factor for overall survival in both the discovery and validation datasets. The final analysis revealed that patients with mild to moderate ARDS [discovery dataset: hazard ratio (HR) =1.719; 95% confidence interval (CI): 1.229-2.406; log-rank test P=0.001; validation dataset: HR =1.874; 95% CI: 1.238-2.837; log-rank test P=0.002] or severe ARDS (discovery dataset: HR =1.874; 95% CI: 1.007-3.488; log-rank test P=0.04; validation dataset: HR =1.698; 95% CI: 1.042-2.768; log-rank test P=0.03) with immune deficiency exhibited lower overall survival rates. Patients with mild to moderate ARDS and immune deficiency showed greater benefits from low-dose corticosteroid treatment (HR =0.409; 95% CI: 0.249-0.671; P<0.001 for interaction), whereas those with severe ARDS and immune deficiency benefitted from both low and high-dose treatments (low corticosteroid: HR =0.299; 95% CI: 0.136-0.654; high corticosteroid: HR =0.458; 95% CI: 0.214-0.981; P=0.005 for interaction).
UNASSIGNED: Immune deficiency is an independent risk factor in ARDS. Incorporating it into the disease severity grading system based on the Berlin criteria may enhance personalized treatment approaches for ARDS patients. These findings warrant further validation through prospective, large-scale, multicenter randomized controlled trials (RCTs).

BACKGROUND: Despite the significance and prevalence of acute respiratory distress syndrome (ARDS), its detection remains highly variable and inconsistent. In this work, we aim to develop an algorithm (ARDSFlag) to automate the diagnosis of ARDS based on the Berlin definition. We also aim to develop a visualization tool that helps clinicians efficiently assess ARDS criteria.
METHODS: ARDSFlag applies machine learning (ML) and natural language processing (NLP) techniques to evaluate Berlin criteria by incorporating structured and unstructured data in an electronic health record (EHR) system. The study cohort includes 19,534 ICU admissions in the Medical Information Mart for Intensive Care III (MIMIC-III) database. The output is the ARDS diagnosis, onset time, and severity.
RESULTS: ARDSFlag includes separate text classifiers trained using large training sets to find evidence of bilateral infiltrates in radiology reports (accuracy of 91.9%±0.5%) and heart failure/fluid overload in radiology reports (accuracy 86.1%±0.5%) and echocardiogram notes (accuracy 98.4%±0.3%). A test set of 300 cases, which was blindly and independently labeled for ARDS by two groups of clinicians, shows that ARDSFlag generates an overall accuracy of 89.0% (specificity = 91.7%, recall = 80.3%, and precision = 75.0%) in detecting ARDS cases.
CONCLUSIONS: To our best knowledge, this is the first study to focus on developing a method to automate the detection of ARDS. Some studies have developed and used other methods to answer other research questions. Expectedly, ARDSFlag generates a significantly higher performance in all accuracy measures compared to those methods.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is an acute respiratory disease characterized by bilateral chest radiolucency and severe hypoxemia. Quzhou Fructus Aurantii ethyl acetate extract (QFAEE), which is prepared from the traditional Chinese respiratory anti-inflammatory natural herb Quzhou Fructus Arantii, has the potential to alleviate ARDS. In this work, we aimed to investigate the potential and mechanism underlying the action of QFAEE on ARDS and how QFAEE modulates the STING pathway to reduce type I interferon release to alleviate the inflammatory response.
METHODS: Lipopolysaccharide (LPS), a potential proinflammatory stimulant capable of causing pulmonary inflammation with edema after nasal drops, was employed to model ARDS in vitro and in vivo. Under QFAEE intervention, the mechanism of action of QFAEE to alleviate ARDS was explored in this study. TREX1-/- mice were sued as a research model for the activation of the congenital STING signaling pathway. The effect of QFAEE on TREX1-/- mice could explain the STING-targeted effect of QFAEE on alleviating the inflammatory response. Our explorations covered several techniques, Western blot, histological assays, immunofluorescence staining, transcriptomic assays and qRT-PCR to determine the potential mechanism of action of QFAEE in antagonizing the inflammatory response in the lungs, as well as the mechanism of action of QFAEE in targeting the STING signaling pathway to regulate the release of type I interferon.
RESULTS: QFAEE effectively alleviates ARDS symptoms in LPS-induced ARDS. We revealed that the mechanism underlying LPS-induced ARDS is the STING-TBK1 signaling pathway and further elucidated the molecular mechanism of QFAEE in the prevention and treatment of ARDS. QFAEE reduced the release of type I interferons by inhibiting the STING-TBK1-IRF3 axis, thus alleviating LPS-induced pneumonia and lung cell death in mice. Another key finding is that activation of the STING pathway by activators or targeted knockdown of the TREX1 gene can also induce ARDS. As expected, QFAEE was found to be an effective protective agent in alleviating ARDS and the antagonistic effect of QFAEE on ARDS was achieved by inhibiting the STING signaling pathway.
CONCLUSIONS: The main anti-inflammatory effect of QFAEE was achieved by inhibiting the STING signaling pathway and reducing the release of type I interferons. According to this mechanism of effect, QFAEE can effectively alleviate ARDS and can be considered a potential therapeutic agent. In addition, the STING pathway plays an essential role in the development and progression of ARDS, and it is a potential target for ARDS therapy.

UNASSIGNED: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS).
UNASSIGNED: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument.
UNASSIGNED: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn\'t continue improving after 3 months. Health-related quality of life didn\'t change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening.
UNASSIGNED: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

BACKGROUND: Lactoferrin (LF) is an iron-binding multifunctional cationic glycoprotein. Previous studies have demonstrated that LF may be a potential drug for treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In this study, we explored the anti-inflammatory effect and mechanism of bovine lactoferrin (bLF) in ALI using the RNA sequencing (RNA-seq) technology and transcriptome analysis.
RESULTS: Based on the differentially expressed genes (DEGs) obtained from RNA-seq of the Lung from mouse model, the bioinformatics workflow was implemented using the BGISEQ-500 platform. The protein-protein interaction (PPI) network was obtained using STRING, and the hub gene was screened using Cytoscape. To verify the results of transcriptome analysis, the effects of bLF on Lipopolysaccharide (LPS)-induced BEAS-2B cells and its anti-reactive oxygen species (ROS), anti-inflammatory, and antiapoptotic effects were studied via Cell Counting Kit-8 (CCK-8) test, active oxygen detection test, ELISA, and western blot assay. Transcriptome analysis revealed that two hub gene modules of DEGs were screened via PPI analysis using the STRING and MCODE plug-ins of Cytoscape. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these core modules are enriched in the PPAR (peroxisome proliferator-activated receptor) and AMPK (AMP-activated protein kinase) signaling pathways. Through cell experiments, our study shows that bLF can inhibit ROS, inflammatory reaction, and LPS-induced BEAS-2B cell apoptosis, which are significantly antagonized by the PPAR-γ inhibitor GW9662.
CONCLUSIONS: This study has suggested that the PPAR-γ pathway is the critical target of bLF in anti-inflammatory reactions and apoptosis of ALI, which provides a direction for further research.

Mesenchymal stem cells (MSCs) have been widely used to treat various inflammatory and immune-related diseases in preclinical and clinical settings. Intravital microscopy (IVM) is considered the gold standard for investigating pathophysiological conditions in living animals. However, the potential for real-time monitoring of MSCs in the pulmonary microenvironment remains underexplored. In this study, we first constructed a lung window and captured changes in the lung at the cellular level under both inflammatory and noninflammatory conditions with a microscope. We further investigated the dynamics and effects of MSCs under two different conditions. Meanwhile, we assessed the alterations in the adhesive capacity of vascular endothelial cells in vitro to investigate the underlying mechanisms of MSC retention in an inflammatory environment. This study emphasizes the importance of the \"lung window\" for live imaging of the cellular behavior of MSCs by vein injection. Moreover, our results revealed that the upregulation of vascular cell adhesion molecule 1 (VCAM1) in endothelial cells post-inflammatory injury could enhance MSC retention in the lung, further ameliorating acute lung injury. In summary, intravital microscopy imaging provides a practical method to investigate the therapeutic effects of MSCs in acute lung injury.

BACKGROUND: Early prediction of acute respiratory distress syndrome (ARDS) of critically ill patients in intensive care units (ICUs) has been intensively studied in the past years. Yet a prediction model trained on data from one hospital might not be well generalized to other hospitals. It is therefore essential to develop an accurate and generalizable ARDS prediction model adaptive to different hospital or medical centers.
METHODS: We analyzed electronic medical records of 200,859 and 50,920 hospitalized patients within 24 h after being diagnosed with ARDS from the Philips eICU Institute (eICU-CRD) and the Medical Information Mart for Intensive Care (MIMIC-IV) dataset, respectively. Patients were sorted into three groups, including rapid death, long stay, and recovery, based on their condition or outcome between 24 and 72 h after ARDS diagnosis. To improve prediction performance and generalizability, a \"pretrain-finetune\" approach was applied, where we pretrained models on the eICU-CRD dataset and performed model finetuning using only a part (35%) of the MIMIC-IV dataset, and then tested the finetuned models on the remaining data from the MIMIC-IV dataset. Well-known machine-learning algorithms, including logistic regression, random forest, extreme gradient boosting, and multilayer perceptron neural networks, were employed to predict ARDS outcomes. Prediction performance was evaluated using the area under the receiver-operating characteristic curve (AUC).
RESULTS: Results show that, in general, multilayer perceptron neural networks outperformed the other models. The use of pretrain-finetune yielded improved performance in predicting ARDS outcomes achieving a micro-AUC of 0.870 for the MIMIC-IV dataset, an improvement of 0.046 over the pretrain model.
CONCLUSIONS: The proposed pretrain-finetune approach can effectively improve model generalizability from one to another dataset in ARDS prediction.

UNASSIGNED: Esophageal pressure (Pes) has been used as a surrogate of pleural pressure (Ppl) to titrate positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) patients. The relationship between Pes and PEEP remains undetermined.
UNASSIGNED: A gastric tube with a balloon catheter was inserted to monitor Pes in moderate to severe ARDS patients who underwent invasive mechanical ventilation. To assess the end-expiratory Pes response (ΔPes) to PEEP changes (ΔPEEP), the PEEP level was decreased and increased subsequently (with an average change of 3 cmH2O). The patients underwent the following two series of PEEP adjustment: (I) from PEEP-3 cmH2O to PEEPbaseline; and (II) from PEEPbaseline to PEEP+3 cmH2O. The patients were classified as \"PEEP-dependent type\" if they had ΔPes ≥30% ΔPEEP and were otherwise classified as \"PEEP-independent type\" (ΔPes <30% ΔPEEP in any series).
UNASSIGNED: In total, 54 series of PEEP adjustments were performed in 18 ARDS patients. Of these patients, 12 were classified as PEEP-dependent type, and six were classified as PEEP-independent type. During the PEEP adjustment, end-expiratory Pes changed significantly in the PEEP-dependent patients, who had a Pes of 10.8 (7.9, 12.3), 12.5 (10.5, 14.9), and 14.5 (13.1, 18.3) cmH2O at PEEP-3 cmH2O, PEEPbaseline, and PEEP+3 cmH2O, respectively (median and quartiles; P<0.0001), while end-expiratory transpulmonary pressure (PL) was maintained at an optimal range [-0.1 (-0.7, 0.4), 0.1 (-0.6, 0.5), and 0.3 (-0.3, 0.7) cmH2O, respectively]. In the PEEP-independent patients, the Pes remained unchanged, with a Pes of 15.4 (11.4, 17.8), 15.5 (11.6, 17.8), and 15.4 (11.7, 18.30) cmH2O at each of the three PEEP levels, respectively. Meanwhile, end-expiratory PL significantly improved [from -5.5 (-8.5, -3.4) at PEEP-3 cmH2O to -2.5 (-5.0, -1.6) at PEEPbaseline to -0.5 (-1.8, 0.3) at PEEP+3 cmH2O; P<0.01].
UNASSIGNED: Two types of Pes phenotypes were identified according to the ΔPes to ΔPEEP. The underlying mechanisms and implications for clinical practice require further exploration.

UNASSIGNED: Current data supporting the use of prone positioning (PP) during venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with acute respiratory distress syndrome (ARDS) are limited. This prospective randomized controlled study aimed to determine whether PP implemented within 24 hours of ECMO can improve survival in these patients.
UNASSIGNED: From June 2021 to July 2023, 97 adult patients receiving VV-ECMO for ARDS in three centers were enrolled and 1:1 randomized into PP (n=49) and control groups (n=48). Patients in the PP group receiving prone positioning, while the control group were maintained in the supine position. The primary outcome was 30-day survival, and secondary outcomes included in-hospital survival and other clinical outcomes.
UNASSIGNED: All 97 patients were included for analysis. Patient characteristics did not significantly differ between the two groups. The median duration of PP was 81 hours, and the median number of PP sessions was 5 times. PP improved oxygenation and ventilator parameters. The incidence of complications during PP was low, with pressure sores being the most frequent (10.2%). The 30-day survival was significantly higher in the PP group (67.3% vs. 45.8%; P=0.033), as was in-hospital survival (61.2% vs. 39.6%; P=0.033). In the PP group, the successful ECMO weaning rate was significantly higher (77.5% vs. 50.0%; P=0.005), and the duration of ECMO support was significantly shorter {10 [8-11] vs. 10 [8-14] days; P=0.038}. However, in subgroup analysis of COVID patients the 30-day survival, in-hospital survival, successful ECMO weaning rate and the duration of ECMO support did not differ between the groups. The duration of mechanical ventilation, length of intensive care unit stay, and length of hospital stay did not significantly differ between the groups.
UNASSIGNED: When initiated within 24 hours of ECMO, PP can improve 30-day survival in patients with ARDS receiving VV-ECMO. In addition, it may improve the successful ECMO weaning rate and reduce the duration of ECMO support. However, considering the limitations, more strictly designed, large sample prospective randomized controlled trials are proposed.
UNASSIGNED: Chinese Clinical Trial Registry ChiCTR2300075326.

The prevalence rate of acute respiratory distress syndrome (ARDS) is estimated at approximately 10% in critically ill patients worldwide, with the mortality rate ranging from 17% to 39%. Currently, ARDS mortality is usually higher in patients with COVID-19, giving another challenge for ARDS treatment. However, the treatment efficacy for ARDS is far from satisfactory. The relationship between the gut microbiota and ARDS has been substantiated by relevant scientific studies. ARDS not only changes the distribution of gut microbiota, but also influences intestinal mucosal barrier through the alteration of gut microbiota. The modulation of gut microbiota can impact the onset and progression of ARDS by triggering dysfunctions in inflammatory response and immune cells, oxidative stress, cell apoptosis, autophagy, pyroptosis, and ferroptosis mechanisms. Meanwhile, ARDS may also influence the distribution of metabolic products of gut microbiota. In this review, we focus on the impact of ARDS on gut microbiota and how the alteration of gut microbiota further influences the immune function, cellular functions and related signaling pathways during ARDS. The roles of gut microbiota-derived metabolites in the development and occurrence of ARDS are also discussed.