急性呼吸窘迫综合症尚未综述的内容

This review discusses the clinical challenges associated with ventilatory support and pharmacological interventions in patients with acute respiratory distress syndrome (ARDS). In addition, it discusses current scientific challenges facing researchers when planning and performing trials of ventilatory support or pharmacological interventions in these patients. Noninvasive mechanical ventilation is used in some patients with ARDS. When intubated and mechanically ventilated, ARDS patients should be ventilated with low tidal volumes. A plateau pressure <30 cmH2O is recommended in all patients. It is suggested that a plateau pressure <15 cmH2O should be considered safe. Patient with moderate and severe ARDS should receive higher levels of positive end-expiratory pressure (PEEP). Rescue therapies include prone position and neuromuscular blocking agents. Extracorporeal support for decapneisation and oxygenation should only be considered when lung-protective ventilation is no longer possible, or in cases of refractory hypoxaemia, respectively. Tracheotomy is only recommended when prolonged mechanical ventilation is expected. Of all tested pharmacological interventions for ARDS, only treatment with steroids is considered to have benefit. Proper identification of phenotypes, known to respond differently to specific interventions, is increasingly considered important for clinical trials of interventions for ARDS. Such phenotypes could be defined based on clinical parameters, such as the arterial oxygen tension/inspiratory oxygen fraction ratio, but biological marker profiles could be more promising. Treatment of ARDS is mainly through the prevention of ventilation-induced lung injury http://ow.ly/DeJC30hGWfi

… Studies were included if they evaluated any fluid responsiveness predictor in adult ARDS … This research received no specific grant from any funding agency in the public, commercial, …

BACKGROUND Thousands of papers on acute respiratory distress syndrome (ARDS) have been published in the last decade. This study aimed to evaluate the research hotspots and future trends in ARDS research using bibliometric analysis. METHODS All relevant literature on ARDS published between 2010 and 2019 was retrieved from the Web of Science Core Collection database, and the retrieval strategy was TS = (ARDS OR acute respiratory distress syndrome). Bibliometric analysis was conducted using VOSviewer and the online bibliometric analysis platform based on retrieved data. Bibliographic Item Co-occurrence Matrix Builder (BICOMB) and gCLUTO software were used to evaluate and visualize the results, and to explore the hotspots in the field of ARDS. RESULTS A total of 9,858 ARDS research articles dated between 2010 and 2019 were included. The dominant position of the United States in global ARDS research throughout this 10-year period was evident, and it was also the country most frequently involved in international cooperation. The University of Toronto was the most productive institution and a leader in research collaboration. Critical Care Medicine was the most productive journal in terms of the number of publications on ARDS. Further, Matthay MA, Pelosi P, Slutsky AS, and Thompson BT all made significant contributions to ARDS research. A total of 37 most frequent keywords were identified and belonged to 5 hotspots: (I) adult and pediatric ARDS; (II) life-support monitoring parameters and therapy in severe patients with ARDS; (III) molecular mechanisms of acute lung injury; (IV) influenza-related pneumonia; and (V) severe complications of ARDS. Also, in the last 5 years, the keywords "biomarkers", "pathway", "NF-κB", "epidemiology", "life-support", and "ECMO" began to appear in the ARDS research field. CONCLUSIONS In the decade from 2010 to 2019, the United States was a global leader in ARDS research, and hotspots included epidemiology, mechanisms, monitoring parameters, and therapy, especially mechanical ventilation. Our results suggest that the mechanisms of ARDS and novel life-support therapies will remain research hotspots in the future. International collaboration is also expected to widen and deepen in the field of ARDS research.

… In conclusion, the study by Isha and colleagues illustrates the potential of the new Global definition of ARDS to broaden the scope of future interventional research. Their work …

Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe respiratory conditions with complex pathogenesis, in which endothelial cells (ECs) play a key role. Despite numerous studies on ALI/ARDS and ECs, a bibliometric analysis focusing on the field is lacking. This study aims to fill this gap by employing bibliometric techniques, offering an overarching perspective on the current research landscape, major contributors, and emerging trends within the field of ALI/ARDS and ECs. Methods Leveraging the Web of Science Core Collection (WoSCC) database, we conducted a comprehensive search for literature relevant to ALI/ARDS and ECs. Utilizing Python, VOSviewer, and CiteSpace, we performed a bibliometric analysis on the corpus of publications within this field. Results This study analyzed 972 articles from 978 research institutions across 40 countries or regions, with a total of 5,277 authors contributing. These papers have been published in 323 different journals, spanning 62 distinct research areas. The first articles in this field were published in 2011, and there has been a general upward trend in annual publications since. The United States, Germany, and China are the principal contributors, with Joe G. N. Garcia from the University of Arizona identified as the leading authority in this field. American Journal of Physiology-Lung Cellular and Molecular Physiology has the highest publication count, while Frontiers in Immunology has been increasingly focusing on this field in recent years. “Cell Biology” stands as the most prolific research area within the field. Finally, this study identifies endothelial glycocalyx, oxidative stress, pyroptosis, TLRs, NF-κB, and NLRP3 as key terms representing research hotspots and emerging frontiers in this field. Conclusion This bibliometric analysis provides a comprehensive overview of the research landscape surrounding ALI/ARDS and ECs. It reveals an increasing academic focus on ALI/ARDS and ECs, particularly in the United States, Germany, and China. Our analysis also identifies several emerging trends and research hotspots, such as endothelial glycocalyx, oxidative stress, and pyroptosis, indicating directions for future research. The findings can guide scholars, clinicians, and policymakers in targeting research gaps and setting priorities to advance the field.

Although the definition of acute respiratory distress syndrome (ARDS) has undergone numerous revisions aimed at enhancing its diagnostic accuracy and clinical practicality, the usefulness and precision of these definitions remain matters of ongoing discussion. In this Position Paper, we report on a Delphi study to reach a consensus on the conceptual model of ARDS, specifically identifying its defining components within clinical, research, and educational contexts as well as exploring the potential role of subphenotyping. We did a four-round Delphi study, involving experts in ARDS research and management from a diverse range of geoeconomic regions and professional backgrounds. Consensus was achieved for the conceptual model of ARDS; key components to be included for an ARDS definition in the context of research, education, and patient management; and the need for further research in subphenotyping ARDS. Additionally, we highlight knowledge gaps and research priorities that could guide future investigations in this area. Our study builds on previous non-Delphi-based consensus processes (eg, the new global definition of ARDS and recent society-based guidelines) by using a rigorous Delphi method that ensured panellist anonymity and used clear quantitative criteria to mitigate potential peer pressure and group conformity. The findings underscore the need to refine the ARDS definition to better account for the heterogeneity of clinical presentations and underlying pathophysiology, and to improve diagnostic precision, including the use of subphenotyping where appropriate.

Aim Acute respiratory distress syndrome or ARDS is an acute, severe form of respiratory failure characterised by poor oxygenation and bilateral pulmonary infiltrates. Advancements in signal processing and machine learning have led to promising solutions for classification, event detection and predictive models in the management of ARDS. Method In this review, we provide systematic description of different studies in the application of Machine Learning (ML) and artificial intelligence for management, prediction, and classification of ARDS. We searched the following databases: Google Scholar, PubMed, and EBSCO from 2009 to 2023. A total of 243 studies was screened, in which, 52 studies were included for review and analysis. We integrated knowledge of previous work providing the state of art and overview of explainable decision models in machine learning and have identified areas for future research. Results Gradient boosting is the most common and successful method utilised in 12 (23.1%) of the studies. Due to limitation of data size available, neural network and its variation is used by only 8 (15.4%) studies. Whilst all studies used cross validating technique or separated database for validation, only 1 study validated the model with clinician input. Explainability methods were presented in 15 (28.8%) of studies with the most common method is feature importance which used 14 times. Conclusion For databases of 5000 or fewer samples, extreme gradient boosting has the highest probability of success. A large, multi-region, multi centre database is required to reduce bias and take advantage of neural network method. A framework for validating with and explaining ML model to clinicians involved in the management of ARDS would be very helpful for development and deployment of the ML model.

Acute respiratory distress syndrome (ARDS) is a multifactorial, inflammatory lung disease with significant morbidity and mortality that predominantly requires supportive care in its management. Although initially described in adult patients, the diagnostic definitions for ARDS have evolved over time to accurately describe this disease process in pediatric and, more recently, neonatal patients. The management of ARDS in each age demographic has converged in the application of lung protective ventilatory strategies to mitigate the primary disease process and prevent its exacerbation by limiting ventilator induced lung injury. However, differences arise in the preferred ventilatory strategies or adjunctive pulmonary therapies used to mitigate each type of ARDS. In this review, we compare and contrast the epidemiology, common etiologies, pathophysiology, diagnostic criteria, and outcomes of ARDS across the lifespan. Additionally, we discuss in detail the different management strategies used for each subtype of ARDS and spotlight how these strategies were applied to mitigate poor outcomes during the COVID-19 pandemic. This review is geared toward both clinicians and clinician-scientists as it not only summarizes the latest information on disease pathogenesis and patient management in ARDS across the lifespan but also highlights knowledge gaps for further investigative efforts. We conclude by projecting how future studies can fill these gaps in research and what improvements may be envisioned in the management of NARDS and PARDS based on the current breadth of literature in adult ARDS treatment strategies.

Acute respiratory distress syndrome (ARDS) is a severe complication of critical illness, characterized by bilateral lung infiltrates and hypoxemia. Its clinical and pathophysiological heterogeneity poses challenges for both diagnosis and treatment. This review outlines the evolution of ARDS definitions, discusses the underlying pathophysiology of ARDS, and examines the clinical implications of its heterogeneity. Traditional ARDS definitions required invasive mechanical ventilation and relied on arterial blood gas measurements to calculate the PaO2/FiO2 ratio. Recent updates have expanded these criteria to include patients receiving noninvasive respiratory support, such as high-flow nasal oxygen, and the adoption of the SpO2/FiO2 ratio as an alternative to the PaO2/FiO2 ratio. While these changes broaden the diagnostic criteria, they also introduce additional complexity. ARDS heterogeneity—driven by varying etiologies, clinical subphenotypes, and underlying biological mechanisms—highlights the limitations of a uniform management approach. Emerging evidence highlights the presence of distinct ARDS subphenotypes, each defined by unique molecular and clinical characteristics, offering a pathway to more precise therapeutic targeting. Advances in omics technologies—encompassing genomics, proteomics, and metabolomics—are paving the way for precision-medicine approaches with the potential to revolutionize ARDS management by tailoring interventions to individual patient profiles. This paradigm shift from broad diagnostic categories to precise, subphenotype-driven care holds promise for redefining the landscape of treatment for ARDS and, ultimately, improving outcomes in this complex, multifaceted syndrome.

Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into “personalized” medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery to greater translational impact and the need for a more streamlined drug approval process. The unmet need for biomarkers in acute respiratory distress syndrome (ARDS) is for reliable and validated biomarkers that minimize heterogeneity and allow for stratification of subject selection for enrollment in clinical trials of tailored therapies. This unmet need is particularly highlighted by the ongoing SARS-CoV-2/COVID-19 pandemic. The unprecedented numbers of COVID-19-induced ARDS cases has strained health care systems across the world and exposed the need for biomarkers that would accelerate drug development and the successful phenotyping of COVID-19-infected patients at risk for development of ARDS and ARDS mortality. Accordingly, this review discusses the current state of ARDS biomarkers in the context of the drug development pipeline and highlight gaps between biomarker discovery and clinical implementation while proposing potential paths forward. We discuss potential ARDS biomarkers by category and by context of use, highlighting progress in the development continuum. We conclude by discussing challenges to successful translation of biomarker candidates to clinical impact and proposing possible novel strategies.

Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities with refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With the outbreak of coronavirus disease 19 worldwide, the mortality of ARDS has increased correspondingly. Comprehending the pathophysiology and the underlying molecular mechanisms of ARDS may thus be essential to developing effective therapeutic strategies and reducing mortality. To facilitate further understanding of its pathogenesis and exploring novel therapeutics, this review provides comprehensive information of ARDS from pathophysiology to molecular mechanisms and presents targeted therapeutics. We first describe the pathogenesis and pathophysiology of ARDS that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance and oxidative stress. Next, we summarize the molecular mechanisms and signaling pathways related to the above four aspects of ARDS pathophysiology, along with the latest research progress. Finally, we discuss the emerging therapeutic strategies that show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies and mesenchymal stromal cell therapies, highlighting the pathophysiological basis and the influences on signal transduction pathways for their use.

Purpose: Implicit bias in medicine is widespread, with minority populations historically underrepresented in research. Studies have shown racial and ethnic disparities in patient outcomes, including in acute respiratory distress syndrome (ARDS). This study examines the representation of minority patients in ARDS research in the USA.

… , and treatment of ARDS [4]. … of ARDS is still unclear. In this chapter, we review the current evidence for biomarkers in several aspects of ARDS management and to identify the gaps that …

… Given the quickly evolving landscape of ARDS research, there is a need for living clinical practice guidelines which will require frequent iterative updates to ensure they accurately …

Over the last decade, the management of acute respiratory distress syndrome (ARDS) has made considerable progress both regarding supportive and pharmacologic therapies. Lung protective mechanical ventilation is the cornerstone of ARDS management. Current recommendations on mechanical ventilation in ARDS include the use of low tidal volume (VT) 4–6 mL/kg of predicted body weight, plateau pressure (PPLAT) < 30 cmH2O, and driving pressure (∆P) < 14 cmH2O. Moreover, positive end-expiratory pressure should be individualized. Recently, variables such as mechanical power and transpulmonary pressure seem promising for limiting ventilator-induced lung injury and optimizing ventilator settings. Rescue therapies such as recruitment maneuvers, vasodilators, prone positioning, extracorporeal membrane oxygenation, and extracorporeal carbon dioxide removal have been considered for patients with severe ARDS. Regarding pharmacotherapies, despite more than 50 years of research, no effective treatment has yet been found. However, the identification of ARDS sub-phenotypes has revealed that some pharmacologic therapies that have failed to provide benefits when considering all patients with ARDS can show beneficial effects when these patients were stratified into specific sub-populations; for example, those with hyperinflammation/hypoinflammation. The aim of this narrative review is to provide an overview on current advances in the management of ARDS from mechanical ventilation to pharmacological treatments, including personalized therapy.

BACKGROUND Acute respiratory distress syndrome (ARDS), an acute respiratory failure caused by noncardiogenic pulmonary edema, was first defined by Ashbaugh et al. in 1967. The number of publications increased enormously after the Berlin definition of ARDS was first described in 2012. OBJECTIVES This article intends to provide the physicians and the scientists with a reference guide to assess the most influential publications written about ARDS. MATERIAL AND METHODS We performed an exhaustive bibliometric analysis to identify publication trends by year, and the most influential research articles, authors, co-authors, journals, and countries. Articles on ARDS published in Science Citation Index (SCI) and Emerging Sources Citation Index (ESCI) journals between 1980 and 2020 were examined. On December 20, 2020, the keywords "ARDS" and "acute respiratory distress syndrome" were searched using the Web of Science Core Collection (WoSCC) database, and data including titles, author information, abstracts, journals, and references were analyzed. RESULTS A total of 4564 articles related to ARDS published between 1980 and 2020 were identified. After excluding 192 proceedings papers, 19 early access papers, 1 book chapter, 1 research paper, and 1 retracted article, 4350 articles published in SCI and ESCI journals were analyzed. The largest number of articles (n = 557, 12.8%) appeared in 2020. The average citations per article was 38.21, and 4350 articles were cited 166,885 times altogether. The USA was at the top of the list of the most productive countries with 5025 articles. Harvard University was the most contributing institution with 244 articles. M.A. Matthay ranked as the most productive author in ARDS research with 87 published publications. CONCLUSION The present study provided a comprehensive, illustrative analysis of ARDS articles published in SCI and ESCI journals over the past 40 years.

COVID-19

Many patients with acute respiratory failure fulfill the diagnosis of Acute Respiratory Distress Syndrome (ARDS), forming a very heterogeneous population. Clinical trials have not yielded beneficial treatment effects in ARDS, possibly caused by this heterogeneity. Dividing patients with ARDS into subgroups, each with similar characteristics, may result in improved treatment strategies as part of a precision medicine approach. In this systematic review, we summarize the subphenotypes identified so far, the current state, and future directions for precision medicine in ARDS. Multiple data-driven subphenotypes have been identified based on a wide range of variables. These subphenotypes are associated with differences in clinical outcomes, which could be used for prognostic- and predictive enrichment of future interventional studies. True treatable traits have not been identified yet, deeper phenotyping will hopefully reveal these along with mechanistic differences.

The management of mechanical ventilation (MV) remains a challenge in intensive care units (ICUs). The digitalization of healthcare and the implementation of artificial intelligence (AI) and machine learning (ML) has significantly influenced medical decision-making capabilities, potentially enhancing patient outcomes. Acute respiratory distress syndrome, an overwhelming inflammatory lung disease, is common in ICUs. Most patients require MV. Prolonged MV is associated with an increased length of stay, morbidity, and mortality. Shortening the MV duration has both clinical and economic benefits and emphasizes the need for better MV weaning management. AI and ML models can assist the physician in weaning patients from MV by providing predictive tools based on big data. Many ML models have been developed in recent years, dealing with this unmet need. Such models provide an important prediction regarding the success of the individual patient’s MV weaning. Some AI models have shown a notable impact on clinical outcomes. However, there are challenges in integrating AI models into clinical practice due to the unfamiliar nature of AI for many physicians and the complexity of some AI models. Our review explores the evolution of weaning methods up to and including AI and ML as weaning aids.

ABSTRACT Introduction Typical acute respiratory distress syndrome (ARDS) and severe coronavirus-19 (COVID-19) pneumonia share complex pathophysiology, a high mortality rate, and an unmet need for efficient therapeutics. Areas covered This review discusses the current advances in understanding the pathophysiologic mechanisms underlying typical ARDS and severe COVID-19 pneumonia, highlighting specific aspects of COVID-19-related acute hypoxemic respiratory failure that require attention. Two models have been proposed to describe the mechanisms of respiratory failure associated with typical ARDS and severe COVID-19 pneumonia. Expert opinion ARDS is defined as a syndrome rather than a distinct pathologic entity. There is great heterogeneity regarding the pathophysiologic, clinical, radiologic, and biological phenotypes in patients with ARDS, challenging clinicians, and scientists to discover new therapies. COVID-19 has been described as a cause of pulmonary ARDS and has reopened many questions regarding the pathophysiology of ARDS itself. COVID-19 lung injury involves direct viral epithelial cell damage and thrombotic and inflammatory reactions. There are some differences between ARDS and COVID-19 lung injury in aspects of aeration distribution, perfusion, and pulmonary vascular responses.

INTRODUCTION Neutrophils are the primary effectors of the innate immune system but are profoundly histotoxic cells. The acute respiratory distress syndrome (ARDS) is considered to be a prime example of neutrophil-mediated tissue injury. SOURCES OF DATA The information presented in this review is acquired from the published neutrophil cell biology literature and the longstanding interest of the senior authors in ARDS pathogenesis and clinical management. AREAS OF AGREEMENT Investigators in the field would agree that neutrophils accumulate in high abundance in the pulmonary microcirculation, lung interstitium and alveolar airspace of patients with ARDS. ARDS is also associated with systemic neutrophil priming and delayed neutrophil apoptosis and clearance of neutrophils from the lungs. In animal models, reducing circulating neutrophil numbers ameliorates lung injury. AREAS OF CONTROVERSY Areas of uncertainty include how neutrophils get stuck in the narrow pulmonary capillary network-whether this reflects changes in the mechanical properties of primed neutrophils alone or additional cell adhesion molecules, the role of neutrophil sub-sets or polarization states including pro-angiogenic and low-density neutrophils, whether neutrophil extracellular trap (NET) formation is beneficial (through bacterial capture) or harmful and the potential for neutrophils to participate in inflammatory resolution. The latter may involve the generation of specialized pro-resolving molecules (SPMs) and MMP-9, which is required for adequate matrix processing. GROWING POINTS Different and possibly stable endotypes of ARDS are increasingly being recognized, yet the relative contribution of the neutrophil to these endotypes is uncertain. There is renewed and intense interest in understanding the complex 'new biology' of the neutrophil, specifically whether this cell might be a valid therapeutic target in ARDS and other neutrophil-driven diseases and developing understanding of ways to enhance the beneficial role of the neutrophil in the resolution phase of ARDS. AREAS TIMELY FOR DEVELOPING RESEARCH Aside from treatment of the precipitating causes of ARDS, and scrupulous fluid, infection and ventilation management, there are no pharmacological interventions for ARDS; this represents an urgent and unmet need. Therapies aimed at reducing overall neutrophil numbers risk secondary infection; hence better ways are needed to reverse the processes of neutrophil priming activation, hyper-secretion and delayed apoptosis while enhancing the pro-resolution functions of the neutrophil.

… to manage acute respiratory failure. ECMO has been employed as a vital intervention, particularly for patients with severe COVID-19-induced acute respiratory distress syndrome (ARDS…

Significance: Acute respiratory distress syndrome (ARDS) is a severe, highly heterogeneous critical illness with staggering mortality that is influenced by environmental factors, such as mechanical ventilation, and genetic factors. Significant unmet needs in ARDS are addressing the paucity of validated predictive biomarkers for ARDS risk and susceptibility that hamper the conduct of successful clinical trials in ARDS and the complete absence of novel disease-modifying therapeutic strategies. Recent Advances: The current ARDS definition relies on clinical characteristics that fail to capture the diversity of disease pathology, severity, and mortality risk. We undertook a comprehensive survey of the available ARDS literature to identify genes and genetic variants (candidate gene and limited genome-wide association study approaches) implicated in susceptibility to developing ARDS in hopes of uncovering novel biomarkers for ARDS risk and mortality and potentially novel therapeutic targets in ARDS. We further attempted to address the well-known health disparities that exist in susceptibility to and mortality from ARDS. Critical Issues: Bioinformatic analyses identified 201 ARDS candidate genes with pathway analysis indicating a strong predominance in key evolutionarily conserved inflammatory pathways, including reactive oxygen species, innate immunity-related inflammation, and endothelial vascular signaling pathways. Future Directions: Future studies employing a system biology approach that combines clinical characteristics, genomics, transcriptomics, and proteomics may allow for a better definition of biologically relevant pathways and genotype–phenotype connections and result in improved strategies for the sub-phenotyping of diverse ARDS patients via molecular signatures. These efforts should facilitate the potential for successful clinical trials in ARDS and yield a better fundamental understanding of ARDS pathobiology.

BackgroundThere is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome.MethodsThis is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality.ResultsFrom eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04).ConclusionsAn adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.

Background Acute respiratory distress syndrome (ARDS) is associated with high mortality rates in critically ill patients. Renopulmonary interplay remains crucial in contributing to the outcomes in patients with ARDS. While the role of acute kidney injury has been widely explored in these patients, there remains an unmet need in the literature about the impact of chronic kidney disease (CKD) in these patients. Research Question Is there a quantifiable association between CKD and in‐hospital outcomes in patients with ARDS? Study Design and Methods We utilized a retrospective study design to compare descriptive statistics and outcomes in patients with ARDS with or without CKD. Pearson’s chi‐square test was used to compare categorical variables, while the Wilcoxon rank sum test was used for continuous variables. We also performed multivariate logistic regression analyses for each outcome and adjusted for demographics and comorbidities. Lastly, we conducted a sensitivity analysis using propensity score–matched outcomes between these groups. Results Among 479,450 patients with ARDS, 17.6% also had CKD, while 82.4% did not. Patients with ARDS and CKD were older (median age: 71 years vs. 60 years, p < 0.001) and comprised a greater proportion of males (59.4% vs. 55.9%, p < 0.001). CKD was associated with increased odds of in‐hospital mortality (adjusted odds ratio [aOR] 1.29, p < 0.001), acute heart failure (aOR 1.26, p < 0.001), ventricular arrhythmias (aOR 1.16, p < 0.001), cardiogenic shock (aOR 1.10, p = 0.044), major adverse cardiovascular events (aOR 1.29, p < 0.001), and length of stay ≥ 7 days (aOR 1.05, p = 0.033). Interpretation Our study provides insights into the magnitude of impact renal diseases may have on the outcomes of patients with ARDS. Further prospective studies are warranted to establish more substantial epidemiological evidence of this relationship to tailor the management of such patients.

The hallmark of acute respiratory distress syndrome (ARDS) pathobiology is unchecked inflammation-driven diffuse alveolar damage and alveolar-capillary barrier dysfunction. Currently, therapeutic interventions for ARDS remain largely limited to pulmonary-supportive strategies, and there is an unmet demand for pharmacologic therapies targeting the underlying pathology of ARDS in patients suffering from the illness. The complement cascade (ComC) plays an integral role in the regulation of both innate and adaptive immune responses. ComC activation can prime an overzealous cytokine storm and tissue/organ damage. The ARDS and acute lung injury (ALI) have an established relationship with early maladaptive ComC activation. In this review, we have collected evidence from the current studies linking ALI/ARDS with ComC dysregulation, focusing on elucidating the new emerging roles of the extracellular (canonical) and intracellular (non-canonical or complosome), ComC (complementome) in ALI/ARDS pathobiology, and highlighting complementome as a vital nexus of the pathobiological connectome for ALI/ARDS via its crosstalking with other systems of the immunome, DAMPome, PAMPome, coagulome, metabolome, and microbiome. We have also discussed the diagnostic/therapeutic potential and future direction of ALI/ARDS care with the ultimate goal of better defining mechanistic subtypes (endotypes and theratypes) through new methodologies in order to facilitate a more precise and effective complement-targeted therapy for treating these comorbidities. This information leads to support for a therapeutic anti-inflammatory strategy by targeting the ComC, where the arsenal of clinical-stage complement-specific drugs is available, especially for patients with ALI/ARDS due to COVID-19.

RATIONALE: The unmet need for effective therapeutic strategies to address the bidirectional perturbation of the lung-brain axis following traumatic brain injury (TBI) or associated with Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is increasingly recognized. Contributing to this unmet need is the absence of reliable biomarkers that reflect the severity of lung-brain axis disruption. We assessed specific potential lung-brain axis biomarkers in TBI and ALI/ARDS subjects and explored the specific influence of exposure to mechanical ventilation. METHODS: Serum biomarker levels from TBI (n=97) and ARDS subjects (n=39) and healthy controls (n=46) were analyzed (MesoScale Discovery ELISA) utilizing a critical illness lung-brain axis biomarker panel (CILBA) that included DAMPS (eNAMPT, S100A8), inflammatory cytokines (IL-6, IL-1β, IL-1RA, TNF-α), vascular biomarkers (PSGL-1, ANG-2), and neurotrauma biomarkers (GFAP or Glial fibrillary acidic protein, NFL or neurofilament light chain, Tau). RESULTS: TBI and ARDS subjects demonstrated significant elevations in each biomarker (compared to controls) with two exceptions: PSGL-1 was exclusively elevated in ARDS and GFAP exclusively elevated in TBI. Mechanically ventilated subjects exposed exhibited significantly DAMP, vascular and neurotrauma biomarker elevations compared to unexposed subjects. With the exception of GFAP, Ang-2, and S100A8, biomarker elevations were linked to ICU days or mortality. CONCLUSIONS: These results highlight overlapping innate immunity dysregulation as a manifestation of lung-brain axis disruption in both TBI- and ARDS-exposed subjects with amplified dysregulation with mechanical ventilation. Additional longitudinal studies of well-phenotyped TBI and ARDS subjects may substantiate the prognostic value of biomarker analyses in assessing the severity of bidirectional lung-brain axis injuries.

Acute respiratory distress syndrome (ARDS) was first described in 1967, and since then there have been a large number of studies addressing its pathogenesis and therapies. Despite intense research efforts, very few therapies for ARDS have been shown to be effective other than the use of lung protection strategies. The scarcity of therapeutic choices is related to the intricate pathogenesis of the syndrome and to insensitive and aspecific criteria to diagnose this profound acute respiratory failure. The aim of this paper is to summarize advances of new ARDS definitions and provide an overview of new relevant signaling pathways that mediate acute lung injury.

OBJECTIVES: This article describes the methodology used for The Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). The PALLIC-2 sought to develop evidence-based clinical recommendations and when evidence was lacking, expert-based consensus statements and research priorities for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS). DATA SOURCES: Electronic searches were conducted using PubMed, Embase, and Cochrane Library (CENTRAL) databases from 2012 to March 2022. STUDY SELECTION: Content was divided into 11 sections related to PARDS, with abstract and full text screening followed by data extraction for studies which met inclusion with no exclusion criteria. DATA EXTRACTION: We used a standardized data extraction form to construct evidence tables, grade the evidence, and formulate recommendations or statements using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. DATA SYNTHESIS: This consensus conference was comprised of a multidisciplinary group of international experts in pediatric critical care, pulmonology, respiratory care, and implementation science which followed standards set by the Institute of Medicine, using the GRADE system and Research And Development/University of California, Los Angeles appropriateness method, modeled after PALICC 2015. The panel of 52 content and four methodology experts had several web-based meetings over the course of 2 years. We conducted seven systematic reviews and four scoping reviews to cover the 11 topic areas. Dissemination was via primary publication listing all statements and separate supplemental publications for each subtopic that include supporting arguments for each recommendation and statement. CONCLUSIONS: A consensus conference of experts from around the world developed recommendations and consensus statements for the definition and management of PARDS and identified evidence gaps which need further research.

The acute respiratory distress syndrome (ARDS) is a severe form of acute hypoxemic respiratory failure caused by an insult to the alveolar-capillary membrane, resulting in a marked reduction of aerated alveoli, increased vascular permeability and subsequent interstitial and alveolar pulmonary edema, reduced lung compliance, increase of physiological dead space, and hypoxemia. Most ARDS patients improve their systemic oxygenation, as assessed by the ratio between arterial partial pressure of oxygen and inspired oxygen fraction, with conventional intensive care and the application of moderate-to-high levels of positive end-expiratory pressure. However, in some patients hypoxemia persisted because the lungs are markedly injured, remaining unresponsive to increasing the inspiratory fraction of oxygen and positive end-expiratory pressure. For decades, mechanical ventilation was the only standard support technique to provide acceptable oxygenation and carbon dioxide removal. Mechanical ventilation provides time for the specific therapy to reverse the disease-causing lung injury and for the recovery of the respiratory function. The adverse effects of mechanical ventilation are direct consequences of the changes in pulmonary airway pressures and intrathoracic volume changes induced by the repetitive mechanical cycles in a diseased lung. In this article, we review 14 major successful and unsuccessful randomized controlled trials conducted in patients with ARDS on a series of techniques to improve oxygenation and ventilation published since 2010. Those trials tested the effects of adjunctive therapies (neuromuscular blocking agents, prone positioning), methods for selecting the optimum positive end-expiratory pressure (after recruitment maneuvers, or guided by esophageal pressure), high-frequency oscillatory ventilation, extracorporeal oxygenation, and pharmacologic immune modulators of the pulmonary and systemic inflammatory responses in patients affected by ARDS. We will briefly comment physiology-based gaps of negative trials and highlight the possible needs to address in future clinical trials in ARDS.

Acute lung injury (ALI) is a complex disease with numerous causes. This review begins with a discussion of disease development from direct or indirect pulmonary insults, as well as varied pathogenesis. The heterogeneous nature of ALI is then elaborated upon, including its epidemiology, clinical manifestations, potential biomarkers, and genetic contributions. Although no medication is currently approved for this devastating illness, supportive care and pharmacological intervention for ALI treatment are summarized, followed by an assessment of the pathophysiological gap between human ALI and animal models. Lastly, current research progress on advanced nanomedicines for ALI therapeutics in preclinical and clinical settings is reviewed, demonstrating new opportunities towards developing an effective treatment for ALI.

… , and resolution of inflammatory lung injury (such as acute respiratory distress syndrome), … gap junctional intercellular communication to neutrophil–alveolar crosstalk during pulmonary …

… A recent randomized trial of mechanical ventilation in acute lung injury (ALI)/adult respiratory distress syndrome (ARDS) demonstrated a 22% relative reduction in mortality rate using 6 …

BACKGROUND The 2023 international pediatric ventilator liberation clinical practice guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects of ventilator liberation. However, due to the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence. RESEARCH QUESTION What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines? STUDY DESIGN and Methods: We conducted systematic reviews of the literature in 8 pre-defined PICO areas related to pediatric ventilator liberation to generate recommendations. Subgroups responsible for each PICO question subsequently identified major research gaps by synthesizing the literature. These gaps were presented at an international symposium at the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) meeting in Spring 2022 for open discussion, feedback was incorporated, and final evaluation of research gaps are summarized in this document. While randomized trials trials (RCTs) represent the highest level of evidence, the panel sought to highlight areas where alternative study designs may also be appropriate, given challenges with conducting large multi-center RCTs in children. RESULTS Significant research gaps were identified in six broad areas related to pediatric ventilator liberation. Several of these areas necessitate multi-center RCTs to provide definitive results, while other gaps can be addressed with multi-center observational studies or quality improvement initiatives. Furthermore, there remains a need for some physiologic studies in several areas, particularly regarding newer diagnostic methods to improve identification of patients at high-risk of extubation failure. INTERPRETATION While pediatric ventilator liberation guidelines have been created, the certainty of evidence remains low and there are multiple research gaps which should be filled through high quality RCTs, and multi-center observational studies and quality improvement initiatives.

Acute lung injury (ALI) is a serious clinical condition that often leads to respiratory failure and high mortality. This review describes the pathogenesis of ALI, including the involvement of inflammatory cytokines, the activation of NLRP3 inflammasome, the generation of oxidative stress, the occurrence of apoptosis, the dysfunction of mitochondrial function, and the breakdown of lung endothelial and epithelial cell barriers. These mechanisms interact to cause significant damage and dysfunction of lung tissue. In addition, the current situation of prevention and treatment of ALI was discussed, with emphasis on lung protective ventilation, fluid management, mesenchymal stem cell therapy and drug therapy. We also analyze the latest research advances in advanced nanomedicine for the treatment of ALI, and the application of this nanomedicine could provide new ideas for the development of effective ALI therapeutics in the future.

… may have anti-inflammatory and cytoprotective effects.26, 27 However, when hypercapnia is compounded by a severe anion-gap acidosis, which frequently occurs during sepsis or …

Pneumonia and its sequelae, acute lung injury, present unique challenges for pulmonary and critical care healthcare professionals, and these challenges have recently garnered global attention due to the ongoing Sars-CoV-2 pandemic. One limitation to translational investigation of acute lung injury, including its most severe manifestation (acute respiratory distress syndrome, ARDS) has been heterogeneity resulting from the clinical and physiologic diagnosis that represents a wide variety of etiologies. Recent efforts have improved our understanding and approach to heterogeneity by defining sub-phenotypes of ARDS although significant gaps in knowledge remain. Improving our mechanistic understanding of acute lung injury and its most common cause, infectious pneumonia, can advance our approach to precision targeted clinical interventions. Here, we review the pathogenesis of pneumonia and acute lung injury, including how respiratory infections and lung injury disrupt lung homoeostasis, and provide an overview of respiratory microbial pathogenesis, the lung microbiome, and interventions that have been demonstrated to improve outcomes—or not—in human clinical trials.

… Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are syndromes with a spectrum of increasing severity of lung injury … A major gap in our knowledge is the …

… Acute lung injury is a life-threatening condition characterized by hypoxemia, pulmonary … into the intricate landscape of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (…

Bone marrow–derived stromal cells (BMSCs) protect against acute lung injury (ALI). To determine the role of BMSC mitochondria in this protection, we airway-instilled mice first with lipopolysaccharide (LPS) and then with either mouse BMSCs (mBMSCs) or human BMSCs (hBMSCs). Live optical studies revealed that the mBMSCs formed connexin 43 (Cx43)-containing gap junctional channels (GJCs) with the alveolar epithelia in these mice, releasing mitochondria-containing microvesicles that the epithelia engulfed. The presence of BMSC-derived mitochondria in the epithelia was evident optically, as well as by the presence of human mitochondrial DNA in mouse lungs instilled with hBMSCs. The mitochondrial transfer resulted in increased alveolar ATP concentrations. LPS-induced ALI, as indicated by alveolar leukocytosis and protein leak, inhibition of surfactant secretion and high mortality, was markedly abrogated by the instillation of wild-type mBMSCs but not of mutant, GJC-incompetent mBMSCs or mBMSCs with dysfunctional mitochondria. This is the first evidence, to our knowledge, that BMSCs protect against ALI by restituting alveolar bioenergetics through Cx43-dependent alveolar attachment and mitochondrial transfer.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are a group of conditions characterized by acute episodes of pulmonary inflammation and increased pulmonary vascular permeability. These conditions often result in severe morbidity and high mortality rates. Increased alveolar-capillary barrier permeability is a pivotal factor in the pathogenesis of ALI/ARDS, and diffuse alveolar epithelial cell (AEC) death is a salient feature of ALI/ARDS. Alveolar epithelium is composed of alveolar type I epithelial cells (AECI) and alveolar type II epithelial cells (AECII), with AECII playing a more critical role. These cells contain a high density of mitochondria in their cytoplasm, and their function depends on mitochondrial quality control (MQC). Existing reviews either focus solely on the mechanisms of AECs and their relationship to lung injury/fibrosis or broadly explore the role of mitochondrial dynamics in lung diseases. However, neither review comprehensively addresses AECII’s MQC and related molecules and signaling pathways. The objective of this study is to investigate the MQC characteristics of AECII in ALI/ARDS, elucidate their role as a regulatory hub for oxidative stress, inflammation, and fibrosis, summarize progress in related clinical trials, and highlight the need for further research to develop effective therapies.

Historically considered a metabolically inert cellular layer separating the blood from the underlying tissue, the endothelium is now recognized as a highly dynamic, metabolically active tissue that is critical to organ homeostasis. Under homeostatic conditions, lung endothelial cells (ECs) in healthy subjects are quiescent, promoting vasodilation, platelet disaggregation, and anti-inflammatory mechanisms. In contrast, lung ECs are essential contributors to the pathobiology of acute respiratory distress syndrome (ARDS), as the quiescent endothelium is rapidly and radically altered upon exposure to environmental stressors, infectious pathogens, or endogenous danger signals into an effective and formidable regulator of innate and adaptive immunity. These dramatic perturbations, produced in a tsunami of inflammatory cascade activation, result in paracellular gap formation between lung ECs, sustained lung edema, and multi-organ dysfunction that drives ARDS mortality. The astonishing plasticity of the lung endothelium in negotiating this inflammatory environment and efforts to therapeutically target the aberrant ARDS endothelium are examined in further detail in this review.

The acute respiratory distress (ARDS) lung is usually characterized by a high degree of inhomogeneity. Indeed, the same lung may show a wide spectrum of aeration alterations, ranging from completely gasless regions, up to hyperinflated areas. This inhomogeneity is normally caused by the presence of lung edema and/or anatomical variations, and is deeply influenced by the gravitational forces.For any given airway pressure generated by the ventilator, the pressure acting directly on the lung (i.e., the transpulmonary pressure or lung stress) is determined by two main factors: 1) the ratio between lung elastance and the total elastance of the respiratory system (which has been shown to vary widely in ARDS patients, between 0.2 and 0.8); and 2) the lung size. In severe ARDS, the ventilatable parenchyma is strongly reduced in size (‘baby lung’); its resting volume could be as low as 300 mL, and the total inspiratory capacity could be reached with a tidal volume of 750–900 mL, thus generating lethal stress and strain in the lung. Although this is possible in theory, it does not explain the occurrence of ventilator-induced lung injury (VILI) in lungs ventilated with much lower tidal volumes. In fact, the ARDS lung contains areas acting as local stress multipliers and they could multiply the stress by a factor ~ 2, meaning that in those regions the transpulmonary pressure could be double that present in other parts of the same lung. These ‘stress raisers’ widely correspond to the inhomogenous areas of the ARDS lung and can be present in up to 40% of the lung.Although most of the literature on VILI concentrates on the possible dangers of tidal volume, mechanical ventilation in fact delivers mechanical power (i.e., energy per unit of time) to the lung parenchyma, which reacts to it according to its anatomical structure and pathophysiological status. The determinants of mechanical power are not only the tidal volume, but also respiratory rate, inspiratory flow, and positive end-expiratory pressure (PEEP). In the end, decreasing mechanical power, increasing lung homogeneity, and avoiding reaching the anatomical limits of the ‘baby lung’ should be the goals for safe ventilation in ARDS.

Acute respiratory distress syndrome (ARDS) remains a life-threatening pulmonary condition with persistently high mortality rates despite significant advancements in supportive care. Its complex pathophysiology involves an intricate interplay of molecular and cellular processes, including cytokine storms, oxidative stress, programmed cell death, and disruption of the alveolar-capillary barrier. These mechanisms drive localized lung injury and contribute to systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Unlike prior reviews that primarily focus on isolated mechanisms, this narrative review synthesizes the key pathophysiological processes of ARDS across molecular, cellular, tissue, and organ levels. By integrating classical theories with recent research advancements, we provide a comprehensive analysis of how inflammatory mediators, metabolic reprogramming, oxidative stress, and immune dysregulation synergistically drive ARDS onset and progression. Furthermore, we critically evaluate current evidence-based therapeutic strategies, such as lung-protective ventilation and prone positioning, while exploring innovative therapies, including stem cell therapy, gene therapy, and immunotherapy. We emphasize the significance of ARDS subtypes and their inherent heterogeneity in guiding the development of personalized treatment strategies. This narrative review provides fresh perspectives for future research, ultimately enhancing patient outcomes and optimizing management approaches in ARDS.

COVID-19 has quickly reached pandemic levels since it was first reported in December 2019. The virus responsible for the disease, named SARS-CoV-2, is enveloped positive-stranded RNA viruses. During its replication in the cytoplasm of host cells, the viral genome is transcribed into proteins, such as the structural protein spike domain S1, which is responsible for binding to the cell receptor of the host cells. Infected patients have initially flu-like symptoms, rapidly evolving to severe acute lung injury, known as acute respiratory distress syndrome (ARDS). ARDS is characterized by an acute and diffuse inflammatory damage into the alveolar-capillary barrier associated with a vascular permeability increase and reduced compliance, compromising gas exchange and causing hypoxemia. Histopathologically, this condition is known as diffuse alveolar damage which consists of permanent damage to the alveoli epithelial cells and capillary endothelial cells, with consequent hyaline membrane formation and eventually intracapillary thrombosis. All of these mechanisms associated with COVID-19 involve the phenotypic expression from different proteins transcription modulated by viral infection in specific pulmonary microenvironments. Therefore, this knowledge is fundamentally important for a better pathophysiological understanding and identification of the main molecular pathways associated with the disease evolution. Evidently, clinical findings, signs and symptoms of a patient are the phenotypic expression of these pathophysiological and molecular mechanisms of SARS-CoV-2 infection. Therefore, no findings alone, whether molecular, clinical, radiological or pathological axis are sufficient for an accurate diagnosis. However, their intersection and/or correlation are extremely critical for clinicians establish the diagnosis and new treatment perspectives.

… Serine proteases can have a direct pathophysiological role in the progression of ARDS. For example, proteinase-3, cathepsin G, and neutrophil elastase (NE) can degrade surfactant D …

… Pathophysiology The pathophysiology of ARDS is complex and our understanding is incomplete due to the inherent limitations of animal models for ARDS and the challenges of …

Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous clinical syndrome encompassing distinct physiological and biological patterns of lung injury. Despite this heterogeneity, the ratio of arterial oxygen partial pressure to inspired oxygen fraction (PaO2/FiO2) remains the cornerstone of ARDS definitions, severity classification, and clinical decision-making. While its simplicity has facilitated widespread use, the PaO2/FiO2 ratio incompletely reflects the underlying physiological mechanisms of hypoxemia and should not be interpreted as a stand-alone marker of disease severity. The PaO2/FiO2 ratio is highly sensitive to ventilator settings, particularly positive end-expiratory pressure (PEEP), exhibits nonlinear behavior at high inspired oxygen fractions, and provides only a static assessment of gas-exchange. Consequently, it fails to capture key dimensions of ARDS pathophysiology, including lung recruitability, mechanical heterogeneity, and the temporal evolution of injury and response to therapy. These limitations are increasingly relevant in contemporary intensive care, where ventilatory strategies and adjunctive therapies actively modify oxygenation independent of structural lung injury. In this narrative review, we critically re-examine the physiological assumptions underlying the PaO2/FiO2 ratio and evaluate its role in current ARDS practice. We synthesize evidence supporting alternative and complementary oxygenation metrics, such as PEEP-adjusted indices, the oxygenation index, and composite measures including the ROX index (SpO2/FiO2 adjusted for respiratory rate), emphasizing their physiological rationale, clinical interpretability, and practical limitations at the bedside. These metrics are discussed not as replacements, but as tools that may refine the contextual interpretation of hypoxemia. Beyond static oxygenation measures, we explore emerging paradigms that conceptualize ARDS severity as a dynamic, multidimensional construct, integrating longitudinal oxygenation trajectories with respiratory mechanics, imaging-based assessment of lung aeration, and biomarker-informed biological subphenotypes. Repositioning the PaO2/FiO2 ratio within this integrated physiological and biological framework may improve patient stratification, enhance the coherence of therapeutic decision-making, in line with the translational goals of modern intensive care.

Acute respiratory distress syndrome (ARDS) is characterized by the acute onset of pulmonary edema of non-cardiogenic origin, along with bilateral pulmonary infiltrates and reduction in respiratory system compliance. The hallmark of the syndrome is refractory hypoxemia. Despite its first description dates back in the late 1970s, a new definition has recently been proposed. However, the definition remains based on clinical characteristic. In the present review, the diagnostic workup and the pathophysiology of the syndrome will be presented. Therapeutic approaches to ARDS, including lung protective ventilation, prone positioning, neuromuscular blockade, inhaled vasodilators, corticosteroids and recruitment manoeuvres will be reviewed. We will underline how a holistic framework of respiratory and hemodynamic support should be provided to patients with ARDS, aiming to ensure adequate gas exchange by promoting lung recruitment while minimizing the risk of ventilator-induced lung injury. To do so, lung recruitability should be considered, as well as the avoidance of lung overstress by monitoring transpulmonary pressure or airway driving pressure. In the most severe cases, neuromuscular blockade, prone positioning, and extra-corporeal life support (alone or in combination) should be taken into account.

The pathophysiology of acute respiratory distress syndrome (ARDS) is marked by inflammation-mediated disruptions in alveolar-capillary permeability, edema formation, reduced alveolar clearance and collapse/derecruitment, reduced compliance, increased pulmonary vascular resistance, and resulting gas exchange abnormalities due to shunting and ventilation-perfusion mismatch. Mechanical ventilation, especially in the setting of regional disease heterogeneity, can propagate ventilator-associated injury patterns including barotrauma/volutrauma and atelectrauma. Lung injury due to the novel coronavirus SARS-CoV-2 resembles other causes of ARDS, though its initial clinical characteristics may include more profound hypoxemia and loss of dyspnea perception with less radiologically-evident lung injury, a pattern not described previously in ARDS.

In recent years, the incidence of acute respiratory distress syndrome (ARDS) has been gradually increasing. Despite advances in supportive care, ARDS remains a significant cause of morbidity and mortality in critically ill patients. ARDS is characterized by acute hypoxaemic respiratory failure with diffuse pulmonary inflammation and bilateral edema due to excessive alveolocapillary permeability in patients with non-cardiogenic pulmonary diseases. Over the past seven decades, our understanding of the pathology and clinical characteristics of ARDS has evolved significantly, yet it remains an area of active research and discovery. ARDS is highly heterogeneous, including diverse pathological causes, clinical presentations, and treatment responses, presenting a significant challenge for clinicians and researchers. In this review, we comprehensively discuss the latest advancements in ARDS research, focusing on its heterogeneity, pathophysiological mechanisms, and emerging therapeutic approaches, such as cellular therapy, immunotherapy, and targeted therapy. Moreover, we also examine the pathological characteristics of COVID-19-related ARDS and discuss the corresponding therapeutic approaches. In the face of challenges posed by ARDS heterogeneity, recent advancements offer hope for improved patient outcomes. Further research is essential to translate these findings into effective clinical interventions and personalized treatment approaches for ARDS, ultimately leading to better outcomes for patients suffering from ARDS.

… identify novel genes and novel gene interactions involved in the pathophysiology of ARDS. … limitations in the clinical setting. A relatively easily accessible lung cell in patients with …

… [62] [63] [64] [65] [66] [67] The balance between these destructive and protective compounds seems to be important in limiting tissue damage in ALI/ARDS.[68] Other potentially injurious …

ABSTRACT Introduction: More than fifty years after the first description of acute respiratory distress syndrome (ARDS) by Ashbaugh and colleagues, no specific treatment of the underlying pathophysiological processes is available. The current therapeutic regime is comprised of supportive measures such as lung protective ventilation, restrictive fluid management, paralyzing drugs, and prone positioning. Although vast improvements have been made in ARDS-treatment during the last five decades, mortality among patients with severe ARDS remains at an unacceptable rate of 45%. Areas covered: This article reviews the evolution of the currently used definition, established pathophysiological mechanism, highlights the current best clinical practice to treat ARDS, gives a brief outlook on cutting edge trends in ARDS research and closes with an expert opinion on the subject. Expert commentary: Individualizing the provided measures to specific genotypes is the key challenge in ARDS research today. The ongoing digital revolution will help to individualize ARDS-treatment and will therefore presumably improve survival and quality of life.

… treatment directed against the pathophysiological mechanisms of ARDS has been identified that … The present study has several limitations. First, it is limited by its retrospective design. …

… importance of echocardiography in ARDS and the available … in ARDS patients. Despite the important progress that echocardiography has gained in the evaluation of patients with ARDS…

Acute respiratory distress syndrome (ARDS) is a common and fatal disease, characterized by lung inflammation, edema, poor oxygenation, and the need for mechanical ventilation, or even extracorporeal membrane oxygenation if the patient is unresponsive to routine treatment. In this review, we aim to explore advances in biomarkers for the diagnosis and treatment of ARDS. In viewing the distinct characteristics of each biomarker, we classified the biomarkers into the following six categories: inflammatory, alveolar epithelial injury, endothelial injury, coagulation/fibrinolysis, extracellular matrix turnover, and oxidative stress biomarkers. In addition, we discussed the potential role of machine learning in identifying and utilizing these biomarkers and reviewed its clinical application. Despite the tremendous progress in biomarker research, there remain nonnegligible gaps between biomarker discovery and clinical utility. The challenges and future directions in ARDS research concern investigators as well as clinicians, underscoring the essentiality of continued investigation to improve diagnosis and treatment.

Identifying new effective treatments for the acute respiratory distress syndrome (ARDS), including COVID-19 ARDS, remains a challenge. The field of ARDS investigation is moving increasingly toward innovative approaches such as the personalization of therapy to biological and clinical sub-phenotypes. Additionally, there is growing recognition of the importance of the global context to identify effective ARDS treatments. This review highlights emerging opportunities and continued challenges for personalizing therapy for ARDS, from identifying treatable traits to innovative clinical trial design and recognition of patient-level factors as the field of critical care investigation moves forward into the twenty-first century.

… acute respiratory distress syndrome (ARDS), it remains challenging to identify patients who … patients with ARDS.[82] Although the application of proteomics for biomarker discovery in ALI …

… role of biomarkers in acute respiratory distress syndrome (ARDS) … Challenges and Future Directions Over the last few decades, we have witnessed an explosion in biomarker discovery. …

… of novel biomarkers into clinical practice is a major challenge because good biomarkers must … established as a composite biomarker for the early diagnosis of ARDS, with a diagnostic …

To date, there is no clinically agreed-upon diagnostic test for acute respiratory distress syndrome (ARDS): the condition is still diagnosed on the basis of a constellation of clinical findings, laboratory tests, and radiological images. Development of ARDS biomarkers has been in a state of continuous flux during the past four decades. To address ARDS heterogeneity, several studies have recently focused on subphenotyping the disease on the basis of observable clinical characteristics and associated blood biomarkers. However, the strong correlation between identified biomarkers and ARDS subphenotypes has yet to establish etiology; hence, there is a need for the adoption of other methodologies for studying ARDS. In this review, we will shed light on ARDS metabolomics research in the literature and discuss advances and major obstacles encountered in ARDS metabolomics research. Generally, the ARDS metabolomics studies focused on identification of differentiating metabolites for diagnosing ARDS, but they were performed to different standards in terms of sample size, selection of control cohort, type of specimens collected, and measuring technique utilized. Virtually none of these studies have been properly validated to identify true metabolomics biomarkers of ARDS. Though in their infancy, metabolomics studies exhibit promise to unfold the biological processes underlying ARDS and, in our opinion, have great potential for pushing forward our present understanding of ARDS.

… Despite hundreds of studies of biomarkers in the acute respiratory distress syndrome (ARDS), there are no biomarkers of ARDS in use in clinical practice [1]. A recent meta-analysis …

Summary In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. Frequently cited reasons for this absence of specific drug therapies include the heterogeneity of patients with ARDS, the potential for a differential response to drugs, and the possibility that the wrong targets have been studied. Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS.

… ARDS. The lack of success of pharmacological therapies for ARDS, however, presents a continued challenge … of previous experience with clinical trials in ARDS, we focus in this Review …

Acute Respiratory Distress Syndrome (ARDS), characterized by the rapid onset of respiratory failure and mortality rates of ~40%, remains a significant challenge in critical care medicine. Despite advances in supportive care, accurate prediction of ARDS mortality remains challenging, resulting in delayed delivery of targeted interventions and effective disease management. Traditional critical illness severity scores lack specificity for ARDS, underscoring the need for more precise prognostic tools for ARDS mortality. To address this crucial gap, we employed a multimodal approach to predict ARDS patients utilizing a comprehensive dataset comprised of integrated clinical, metabolomic, and biochemical/cytokine data from ARDS patients (collected within hours of ICU admission) to develop and validate predictive models of ARDS mortality risk. The most robust multimodal data model generated demonstrated superior predictive capability with an area under the curve (AUC) of 0.868 on the test set and 0.959 on the validation set. Notably, this model achieved perfect specificity in identifying non-survivors in the validation cohort, highlighting potential utility in guiding early and targeted interventions in ICU settings. Metabolomic analysis revealed significant alterations in crucial pathways associated with ARDS mortality with tryptophan metabolism, particularly the kynurenine pathway, emerging as the most significantly enriched metabolic route, as well as the NAD+ metabolism/ nicotinamide phosphoribosyltransferase (NAMPT) and glycosaminoglycan biosynthesis pathways. These metabolic derangements were strongly confirmed by lipidomic/metabolomic analysis of lung tissues from a porcine sepsis/ARDS model. Together, these findings demonstrate the promise of integrating multimodal data to improve ARDS prognostication and to provide important insights into the complex metabolic derangements underlying severe ARDS. Identification of metabolic signatures, such as kynurenine and NAD+ metabolism/NAMPT pathways, may serve as a foundation for developing personalized and effective targeted interventions and management strategies for ARDS patients.

The lack of successful clinical trials in acute respiratory distress syndrome (ARDS) has highlighted the unmet need for biomarkers predicting ARDS mortality and for novel therapeutics to reduce ARDS mortality. We utilized a systems biology multi-“omics” approach to identify predictive biomarkers for ARDS mortality. Integrating analyses were designed to differentiate ARDS non-survivors and survivors (568 subjects, 27% overall 28-day mortality) using datasets derived from multiple ‘omics’ studies in a multi-institution ARDS cohort (54% European descent, 40% African descent). ‘Omics’ data was available for each subject and included genome-wide association studies (GWAS, n = 297), RNA sequencing (n = 93), DNA methylation data (n = 61), and selective proteomic network analysis (n = 240). Integration of available “omic” data identified a 9-gene set (TNPO1, NUP214, HDAC1, HNRNPA1, GATAD2A, FOSB, DDX17, PHF20, CREBBP) that differentiated ARDS survivors/non-survivors, results that were validated utilizing a longitudinal transcription dataset. Pathway analysis identified TP53-, HDAC1-, TGF-β-, and IL-6-signaling pathways to be associated with ARDS mortality. Predictive biomarker discovery identified transcription levels of the 9-gene set (AUC-0.83) and Day 7 angiopoietin 2 protein levels as potential candidate predictors of ARDS mortality (AUC-0.70). These results underscore the value of utilizing integrated “multi-omics” approaches in underpowered datasets from racially diverse ARDS subjects.

Abstract Sepsis affects around 50 million people annually and is a significant contributor to acute respiratory distress syndrome (ARDS), leading to high morbidity and mortality. Sepsis-induced ARDS is the leading cause of ARDS globally and has worse outcomes compared to other causes, with mortality rates up to 40% in severe instances. Geographic variability in ARDS prevalence is notable, with rates of 27% among septic patients in China, 6–7% in Western countries, and up to 31% in sub-Saharan African Intensive Care Units, highlighting significant disparities in disease burden and outcomes. Management of sepsis-induced ARDS generally necessitates mechanical ventilation, yet extended ventilatory support can lead to negative outcomes. Weaning from ventilation is complicated by the inflammatory response and multiorgan dysfunction seen in sepsis. Traditional weaning predictors, like the rapid shallow breathing index, show inadequate sensitivity and specificity, indicating a requirement for more effective predictive tools. Recent studies have identified several biomarkers, including Pancreatic Stone Protein, soluble receptor for advanced glycation end-products, and soluble urokinase plasminogen activator receptor, as promising tools for enhancing the prediction of mechanical ventilation outcomes in sepsis-induced ARDS. Despite the identification of multiple biomarkers, a major clinical gap remains: there is currently no consensus on their routine use to guide weaning, largely due to inconsistent findings, heterogeneity in study designs, and limited large-scale validation. This review explores the role of circulating and respiratory biomarkers in improving outcomes for patients with sepsis-induced ARDS, particularly in predicting successful mechanical ventilation weaning. It appraises the evidence surrounding these biomarkers against traditional weaning indices and identifies gaps in existing research. The review emphasizes the strengths and limitations of current studies, suggesting that validated biomarker-guided strategies could significantly enhance clinical management by reducing ventilation duration, preventing extubation failures, and improving survival rates in this vulnerable patient group.

Despite advances in critical care, acute respiratory distress syndrome (ARDS) remains a potentially life-threatening condition with high mortality. The heterogeneous nature of ARDS, caused by diverse etiologies, poses considerable challenges to accurate diagnosis, treatment, and prognosis. Conventional methods often fail to elucidate the pathophysiology of ARDS, thus limiting therapeutic efficacy. However, recent advances in omics technologies, including genomics, transcriptomics, proteomics, metabolomics, lipidomics, and epigenomics, have provided deeper insights into ARDS mechanisms. Genomic studies have identified genetic variants associated with ARDS susceptibility, such as polymorphisms in genes encoding angiotensin-converting enzyme, surfactant proteins, toll-like receptor 4, interleukin-6, Fas/FasL, and vascular endothelial growth factor, offering potential therapeutic targets. Transcriptomic and proteomic reveal distinct biomarker profiles associated with ARDS pathogenesis, including dysregulated inflammatory signaling, epithelial and endothelial barrier dysfunction, and compromised immune responses. Metabolomics has highlighted biomarkers, such as phenylalanine and choline, aiding in severity assessment, subphenotype stratification, and treatment response prediction. Lipidomics has uncovered disruptions in lipid metabolism, including altered phospholipids, sphingolipids, and eicosanoids, with key lipid species such as lysophosphatidylcholine and ceramide emerging as biomarkers for severity and outcomes. Epigenomics explores DNA methylation, histone modifications, and non-coding RNAs, revealing their role in regulating inflammation, immune responses, and tissue repair in ARDS. These epigenetic changes hold promise for biomarker discovery and personalized therapy. Integrating these omics technologies advances our understanding of ARDS pathophysiology, enabling precision medicine approaches. This review examines the latest advancements in omics research related to ARDS, emphasizing its role in developing personalized diagnostics and therapeutic strategies to improve disease monitoring, prognosis, and treatment outcomes.

Acute respiratory distress syndrome (ARDS) can be induced by multiple clinical factors, including sepsis, acute pancreatitis, trauma, intestinal ischemia/reperfusion and burns. However, these factors alone may poorly explain the risk and outcomes of ARDS. Emerging evidence suggests that genomic-based or transcriptomic-based biomarkers may hold the promise to establish predictive or prognostic stratification methods for ARDS, and also to help in developing novel therapeutic targets for ARDS. Notably, genetic/epigenetic variations correlated with susceptibility and prognosis of ARDS and circulating microRNAs have emerged as potential biomarkers for diagnosis or prognosis of ARDS. Although limited by sample size, ethnicity and phenotypic heterogeneity, ongoing genetic/transcriptomic research contributes to the characterization of novel biomarkers and ultimately helps to develop innovative therapeutics for ARDS patients.

The acute respiratory distress syndrome (ARDS) is a severe lung disorder with a high morbidity and mortality which affects all age groups. Despite active research with intense, ongoing attempts in developing pharmacological agents to treat ARDS, its mortality rate remains unaltered high and treatment is still only supportive. Over the years, there have been many attempts to identify meaningful subgroups likely to react differently to treatment among the heterogenous ARDS population, most of them unsuccessful. Only recently, analysis of large ARDS cohorts from randomized controlled trials have identified the presence of distinct biological subphenotypes among ARDS patients: a hypoinflammatory (or uninflamed; named P1) and a hyperinflammatory (or reactive; named P2) subphenotype have been proposed and corroborated with existing retrospective data. The hyperinflammatory subphenotyope was clearly associated with shock state, metabolic acidosis, and worse clinical outcomes. Core features of the respective subphenotypes were identified consistently in all assessed cohorts, independently of the studied population, the geographical location, the study design, or the analysis method. Additionally and clinically even more relevant treatment efficacies, as assessed retrospectively, appeared to be highly dependent on the respective subphenotype. This discovery launches a promising new approach to targeted medicine in ARDS. Even though it is now widely accepted that each ARDS subphenotype has distinct functional, biological, and mechanistic differences, there are crucial gaps in our knowledge, hindering the translation to bedside application. First of all, the underlying driving biological factors are still largely unknown, and secondly, there is currently no option for fast and easy identification of ARDS subphenotypes. This narrative review aims to summarize the evidence in biological subphenotyping in ARDS and tries to point out the current issues that will need addressing before translation of biological subohenotypes into clinical practice will be possible.

Acute respiratory distress syndrome (ARDS), manifested by intricate etiology and pathophysiology, demands careful clinical surveillance due to its high mortality and imminent life support measures. NMR based metabolomics provides an approach for ARDS which culminates from a wide spectrum of illness thereby confounding early manifestation and prognosis predictors. 1H NMR with its manifold applications in critical disease settings can unravel the biomarker of ARDS thus holding potent implications by providing surrogate endpoints of clinical utility. NMR metabolomics which is the current apogee platform of omics trilogy is contributing towards the possible panacea of ARDS by subsequent validation of biomarker credential on larger datasets. In the present review, the physiological derangements that jeopardize the whole metabolic functioning in ARDS are exploited and the biomarkers involved in progression are addressed and substantiated. The following sections of the review also outline the clinical spectrum of ARDS from the standpoint of NMR based metabolomics which is an emerging element of systems biology. ARDS is the main premise of intensivists textbook, which has been thoroughly reviewed along with its incidence, progressive stages of severity, new proposed diagnostic definition, and the preventive measures and the current pitfalls of clinical management. The advent of new therapies, the need for biomarkers, the methodology and the contemporary promising approaches needed to improve survival and address heterogeneity have also been evaluated. The review has been stepwise illustrated with potent biometrics employed to selectively pool out differential metabolites as diagnostic markers and outcome predictors. The following sections have been drafted with an objective to better understand ARDS mechanisms with predictive and precise biomarkers detected so far on the basis of underlying physiological parameters having close proximity to diseased phenotype. The aim of this review is to stimulate interest in conducting more studies to help resolve the complex heterogeneity of ARDS with biomarkers of clinical utility and relevance.

… Addressing and managing uncertainty for the case scenario requires consideration … , ventilator independence, and adverse effects on quality of life for survivors. In this paper, ALI/ARDS …

Purpose Coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) was an emergent syndrome that led to high volumes of critically ill ventilated patients. We explored influences on decision-making regarding management of COVID-19 ARDS mechanical ventilation to identify modifiable factors to improve preparedness for future pandemics. Methods A systematic review and small group interviews informed the development of an international questionnaire (UK, Italy, Germany and Netherlands) on factors influencing COVID-19 ARDS ventilation decision-making in critical care professionals. Participants ranked four themes in order of importance: disease (uncertainties around COVID-19 ARDS), contextual (cognitive strain), environmental (structural logistics) and team factors. Participants also ranked the subthemes within each theme. Thematic analysis was used to derive findings from qualitative data. Kruskal-Wallis, Mann-Whitney U and Kendall’s tau were used for quantitative data analysis. Results Patient factors (comorbidities, clinical/biochemical parameters) were the most studied influences in the extant literature on decision-making; uncertainty was one of the least studied. 371 critical care professionals responded to the questionnaire. Disease uncertainty (lack of applicable guidelines, unfamiliarity with pathophysiology) was ranked as the most important influence on ventilation decision-making for COVID-19 ARDS across regions, professions and experience levels (p<0.001). Participants expressed underconfidence in their decision-making (median score: 9/20); this was unaffected by experience (p=0.79) or profession (p=0.58). Qualitative findings supported and extended the initial proposed influences, including the impact of team factors (+ve) and resource limitations (−ve) on disease uncertainty. Conclusion Future pandemic preparedness programmes should target modifiable influences such as information sharing, teamworking and resource limitations to mitigate against the negative influence of uncertainty and thereby improve decision-making overall.

… clinical, diagnostic and therapeutic work-up of ARDS. Respiratory mechanics might foster an … ARDS ‘phenotype’) and become the target of personalized mechanical ventilation settings. …

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume ( V T ) is a standard of care, further individualization of V T may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust V T and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.

Acute respiratory distress syndrome (ARDS) has traditionally been managed with population-based, protocolized mechanical ventilation strategies designed to limit ventilator-induced lung injury. While these approaches have improved outcomes, they fail to account for the pronounced biological, mechanical, radiological, and temporal heterogeneity that characterizes ARDS. Accumulating evidence shows that patients differ markedly in functional lung size, recruitability, chest wall mechanics, inflammatory burden, and tolerance to ventilatory stress, making uniform ventilatory targets physiologically imprecise and, at times, harmful. This narrative review examines the evolution from conventional lung-protective ventilation toward a precision-based paradigm that aligns ventilatory support with individual patient physiology. We conceptualize ARDS not as a static syndrome but as a dynamic spectrum, viewing the injured lung as a heterogeneous mechanical system susceptible to regionally amplified stress and strain. Within this framework, we discuss key principles underlying precision ventilation, including functional lung size (the “baby lung”), driving pressure, mechanical power, patient–ventilator interaction, spontaneous breathing-associated injury, and the time-dependent evolution of lung mechanics. We synthesize current evidence supporting mechanical, biological, and radiological subphenotyping as complementary strategies to individualize ventilatory management, while critically appraising their current limitations. This review also evaluates bedside tools that may operationalize precision ventilation in clinical practice, including esophageal pressure monitoring, lung ultrasound, and electrical impedance tomography, and examines the role of artificial intelligence as a clinician-directed decision-support aid rather than a prescriptive substitute for physiological reasoning. Implications for clinical trial design, ethical considerations, and future directions toward predictive and adaptive ventilation strategies are also addressed. Precision mechanical ventilation represents a shift from rigid thresholds toward proportional, physiology-guided intervention across the disease trajectory. By integrating evolving lung mechanics, ventilatory load, and patient effort over time, this approach provides a coherent framework for safer and more effective mechanical ventilation in ARDS while preserving the core principles of lung protection.

Acute respiratory distress syndrome (ARDS) remains one of the leading causes of morbidity and mortality in critically ill patients despite advancements in the field. Mechanical ventilatory strategies are a vital component of ARDS management to prevent secondary lung injury and improve patient outcomes. Multiple strategies including utilization of low tidal volumes, targeting low plateau pressures to minimize barotrauma, using low FiO2 (fraction of inspired oxygen) to prevent injury related to oxygen free radicals, optimization of positive end expiratory pressure (PEEP) to maintain or improve lung recruitment, and utilization of prone ventilation have been shown to decrease morbidity and mortality. The role of other mechanical ventilatory strategies like non-invasive ventilation, recruitment maneuvers, esophageal pressure monitoring, determination of optimal PEEP, and appropriate patient selection for extracorporeal support is not clear. In this article, we review evidence-based mechanical ventilatory strategies and ventilatory adjuncts for ARDS.

… (ARDS). This section will review key aspects of mechanical ventilation in patients with ALI/ARDS, and … leave considerable uncertainty in their appropriate interpretation. Presentations of …

… 300) requiring invasive mechanical ventilation to one of several … to determine whether ARDS had developed within the first … and diagnostic uncertainty of human ARDS that is not present …

Contemplating the future should be grounded in history. The rise of post-polio ICUs was inextricably related to mechanical ventilation. Critically ill patients who developed acute respiratory failure often had “congestive atelectasis” (ie, a term used to describe ARDS prior to 1967). Initial mechanical ventilation strategies for treating this condition and others inadvertently led to ventilator-induced lung injury. Both injurious ventilation and later use of overly cautious weaning practices resulted from both limited technology and understanding of ARDS and other aspects of critical illness. The resulting misperceptions, misconceptions, and missed opportunities took decades to rectify and in some instances still persist. This suggests a reluctance to acknowledge that all therapeutic strategies reflect the historical period in which they were developed and the corresponding limited understanding of ARDS pathophysiology at that time. We are at the threshold of a revolutionary moment in critical care. The confluence of enormous clinical data production, massive computing power, advances in understanding the biomolecular and genetic aspects of critical illness, and the emergence of neural networks will have enormous impact on how critical care is practiced in the decades to come. Therefore, it is imperative we understand the long-crooked path needed to reach the era of protective ventilation in order to avoid similar mistakes moving forward. The emerging era is as difficult to fathom as our current practices and technologies were to those practicing 60 years ago. This review explores the history of mechanical ventilation in treating ARDS, describes current protective ventilation strategies, and speculates how ARDS management might look 20 years from now.

Acute respiratory distress syndrome (ARDS) is characterized by severe inflammatory response and hypoxemia. The use of mechanical ventilation (MV) for correction of gas exchange can cause worsening of this inflammatory response, called “ventilator-induced lung injury” (VILI). The process of withdrawing mechanical ventilation, referred to as weaning from MV, may cause worsening of lung injury by spontaneous ventilation. Currently, there are few specific studies in patients with ARDS. Herein, we reviewed the main aspects of spontaneous ventilation and also discussed potential methods to predict the failure of weaning in this patient category. We also reviewed new treatments (modes of mechanical ventilation, neuromuscular blocker use, and extracorporeal membrane oxygenation) that could be considered in weaning ARDS patients from MV.

BACKGROUND Supplemental oxygen is frequently administered to patients with acute respiratory distress syndrome (ARDS), including ARDS secondary to viral illness such as coronavirus disease 19 (COVID-19). An up-to-date understanding of how best to target this therapy (e.g. arterial partial pressure of oxygen (PaO2) or peripheral oxygen saturation (SpO2) aim) in these patients is urgently required. OBJECTIVES To address how oxygen therapy should be targeted in adults with ARDS (particularly ARDS secondary to COVID-19 or other respiratory viruses) and requiring mechanical ventilation in an intensive care unit, and the impact oxygen therapy has on mortality, days ventilated, days of catecholamine use, requirement for renal replacement therapy, and quality of life. SEARCH METHODS We searched the Cochrane COVID-19 Study Register, CENTRAL, MEDLINE, and Embase from inception to 15 May 2020 for ongoing or completed randomized controlled trials (RCTs). SELECTION CRITERIA Two review authors independently assessed all records in accordance with standard Cochrane methodology for study selection. We included RCTs comparing supplemental oxygen administration (i.e. different target PaO2 or SpO2 ranges) in adults with ARDS and receiving mechanical ventilation in an intensive care setting. We excluded studies exploring oxygen administration in patients with different underlying diagnoses or those receiving non-invasive ventilation, high-flow nasal oxygen, or oxygen via facemask. DATA COLLECTION AND ANALYSIS One review author performed data extraction, which a second review author checked. We assessed risk of bias in included studies using the Cochrane 'Risk of bias' tool. We used the GRADE approach to judge the certainty of the evidence for the following outcomes; mortality at longest follow-up, days ventilated, days of catecholamine use, and requirement for renal replacement therapy. MAIN RESULTS We identified one completed RCT evaluating oxygen targets in patients with ARDS receiving mechanical ventilation in an intensive care setting. The study randomized 205 mechanically ventilated patients with ARDS to either conservative (PaO2 55 to 70 mmHg, or SpO2 88% to 92%) or liberal (PaO2 90 to 105 mmHg, or SpO2 ≥ 96%) oxygen therapy for seven days. Overall risk of bias was high (due to lack of blinding, small numbers of participants, and the trial stopping prematurely), and we assessed the certainty of the evidence as very low. The available data suggested that mortality at 90 days may be higher in those participants receiving a lower oxygen target (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.03 to 3.27). There was no evidence of a difference between the lower and higher target groups in mean number of days ventilated (14.0, 95% CI 10.0 to 18.0 versus 14.5, 95% CI 11.8 to 17.1); number of days of catecholamine use (8.0, 95% CI 5.5 to 10.5 versus 7.2, 95% CI 5.9 to 8.4); or participants receiving renal replacement therapy (13.7%, 95% CI 5.8% to 21.6% versus 12.0%, 95% CI 5.0% to 19.1%). Quality of life was not reported. AUTHORS' CONCLUSIONS We are very uncertain as to whether a higher or lower oxygen target is more beneficial in patients with ARDS and receiving mechanical ventilation in an intensive care setting. We identified only one RCT with a total of 205 participants exploring this question, and rated the risk of bias as high and the certainty of the findings as very low. Further well-conducted studies are urgently needed to increase the certainty of the findings reported here. This review should be updated when more evidence is available.

BACKGROUND: This document provides evidence-based clinical practice guidelines on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS). METHODS: A multidisciplinary panel conducted systematic reviews and metaanalyses of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations. RESULTS: O) (moderate confidence in effect estimates). For patients with severe ARDS, the recommendation is strong for prone positioning for more than 12 h/d (moderate confidence in effect estimates). For patients with moderate or severe ARDS, the recommendation is strong against routine use of high-frequency oscillatory ventilation (high confidence in effect estimates) and conditional for higher positive end-expiratory pressure (moderate confidence in effect estimates) and recruitment maneuvers (low confidence in effect estimates). Additional evidence is necessary to make a definitive recommendation for or against the use of extracorporeal membrane oxygenation in patients with severe ARDS. CONCLUSIONS: The panel formulated and provided the rationale for recommendations on selected ventilatory interventions for adult patients with ARDS. Clinicians managing patients with ARDS should personalize decisions for their patients, particularly regarding the conditional recommendations in this guideline.

Care for patients with acute respiratory distress syndrome (ARDS) has changed considerably over the 50 years since its original description. Indeed, standards of care continue to evolve as does how this clinical entity is defined and how patients are grouped and treated in clinical practice. In this narrative review we discuss current standards – treatments that have a solid evidence base and are well established as targets for usual care – and also evolving standards – treatments that have promise and may become widely adopted in the future. We focus on three broad domains of ventilatory management, ventilation adjuncts, and pharmacotherapy. Current standards for ventilatory management include limitation of tidal volume and airway pressure and standard approaches to setting PEEP, while evolving standards might focus on limitation of driving pressure or mechanical power, individual titration of PEEP, and monitoring efforts during spontaneous breathing. Current standards in ventilation adjuncts include prone positioning in moderate-severe ARDS and veno-venous extracorporeal life support after prone positioning in patients with severe hypoxemia or who are difficult to ventilate. Pharmacotherapy current standards include corticosteroids for patients with ARDS due to COVID-19 and employing a conservative fluid strategy for patients not in shock; evolving standards may include steroids for ARDS not related to COVID-19, or specific biological agents being tested in appropriate sub-phenotypes of ARDS. While much progress has been made, certainly significant work remains to be done and we look forward to these future developments.

ABSTRACT Introduction Although there has been extensive research on mechanical ventilation for acute respiratory distress syndrome (ARDS), treatment remains mainly supportive. Recent studies and new ventilatory modes have been proposed to manage patients with ARDS; however, the clinical impact of these strategies remains uncertain and not clearly supported by guidelines. The aim of this narrative review is to provide an overview and update on ventilatory management for patients with ARDS. Areas covered This article reviews the literature regarding mechanical ventilation in ARDS. A comprehensive overview of the principal settings for the ventilator parameters involved is provided as well as a report on the differences between controlled and assisted ventilation. Additionally, new modes of assisted ventilation are presented and discussed. The evidence concerning rescue strategies, including recruitment maneuvers and extracorporeal membrane oxygenation support, is analyzed. PubMed, EBSCO, and the Cochrane Library were searched up until June 2023, for relevant literature. Expert opinion Available evidence for mechanical ventilation in cases of ARDS suggests the use of a personalized mechanical ventilation strategy. Although promising, new modes of assisted mechanical ventilation are still under investigation and guidelines do not recommend rescue strategies as the standard of care. Further research on this topic is required.

Introduction Acute respiratory distress syndrome (ARDS) is characterized by acute, diffuse, inflammatory lung injury leading to increased pulmonary vascular permeability, pulmonary oedema and loss of aerated tissue. Previous literature showed that restrictive fluid therapy in ARDS shortens time on mechanical ventilation and length of ICU-stay. However, the effect of intravenous fluid use on mortality remains uncertain. We investigated the relationship between cumulative fluid balance (FB), time on mechanical ventilation and mortality in ARDS patients. Materials and methods Retrospective observational study. Patients were divided in four cohorts based on cumulative FB on day 7 of ICU-admission: ≤0 L (Group I); 0–3.5 L (Group II); 3.5–8 L (Group III) and ≥8 L (Group IV). In addition, we used cumulative FB on day 7 as continuum as a predictor of mortality. Primary outcomes were 28-day mortality and ventilator-free days. Secondary outcomes were 90-day mortality and ICU length of stay. Results Six hundred ARDS patients were included, of whom 156 (26%) died within 28 days. Patients with a higher cumulative FB on day 7 had a longer length of ICU-stay and fewer ventilator-free days on day 28. Furthermore, after adjusting for severity of illness, a higher cumulative FB was associated with 28-day mortality (Group II, adjusted OR (aOR) 2.1 [1.0–4.6], p = 0.045; Group III, aOR 3.3 [1.7–7.2], p = 0.001; Group IV, aOR 7.9 [4.0–16.8], p<0.001). Using restricted cubic splines, a non-linear dose-response relationship between cumulative FB and probability of death at day 28 was found; where a more positive FB predicted mortality and a negative FB showed a trend towards survival. Conclusions A higher cumulative fluid balance is independently associated with increased risk of death, longer time on mechanical ventilation and longer length of ICU-stay in patients with ARDS. This underlines the importance of implementing restrictive fluid therapy in ARDS patients.

Spontaneous respiratory effort during mechanical ventilation has long … of ventilation is increasing. Notwithstanding the central place of spontaneous breathing in mechanical ventilation, …

… and uncertain panorama of pharmacological therapies for ARDS, innovative ventilation … Innovations in MV for ARDS encompass emerging technologies aimed at improving patient …

… the current ventilator care goal for patients with ARDS. Some … to the ventilatory management of patients with ARDS, we … for which there is some uncertainty as to the most appropriate set …

BACKGROUND Acute Respiratory Distress Syndrome (ARDS) necessitates personalized treatment strategies due to its heterogeneity, aiming to mitigate Ventilator-Induced Lung Injury (VILI). Advanced monitoring techniques, including imaging, driving pressure, transpulmonary pressure, and mechanical power, present potential avenues for tailored interventions. OBJECTIVE To review some of the most important techniques for achieving greater personalization of mechanical ventilation in ARDS patients as evaluated in randomized clinical trials, by analyzing their effect on three clinically relevant aspects: mortality, ventilator-free days, and gas exchange. METHODS Following PRISMA guidelines, we conducted a systematic review and meta-analysis of Randomized Clinical Trials (RCTs) involving adult ARDS patients undergoing personalized ventilation adjustments. Outcomes were mortality (primary end-point), ventilator-free days, and oxygenation improvement. RESULTS Among 493 identified studies, 13 RCTs (n = 1255) met inclusion criteria. No personalized ventilation strategy demonstrated superior outcomes compared to traditional protocols. Meta-analysis revealed no significant reduction in mortality with image-guided (RR 0.88, 95 % CI 0.70-1.11), driving pressure-guided (RR 0.61, 95 % CI 0.29-1.30), or transpulmonary pressure-guided (RR 0.85, 95 % CI 0.58-1.24) strategies. Ventilator-free days and oxygenation outcomes showed no significant differences. CONCLUSION Our study does not support the superiority of personalized ventilation techniques over traditional protocols in ARDS patients. Further research is needed to standardize ventilation strategies and determine their impact on mechanical ventilation outcomes.

… prediction models for mortality in moderate to severe ARDS, … usefulness were summarized across models. The pooled … effects models both overall and in subgroups of models and study …

Background Acute respiratory distress syndrome (ARDS) is a critical condition commonly encountered in the intensive care unit (ICU), characterized by a high incidence and substantial mortality rate. Early detection and accurate prediction of ARDS can significantly improve patient outcomes. While machine learning (ML) models are increasingly being used for ARDS prediction, there is a lack of consensus on the most effective model or methodology. This study is the first to systematically evaluate the performance of ARDS prediction models based on multiple quantitative data sources. We compare the effectiveness of ML models via a meta-analysis, revealing factors affecting performance and suggesting strategies to enhance generalization and prediction accuracy. Objective This study aims to evaluate the performance of existing ARDS prediction models through a systematic review and meta-analysis, using metrics such as area under the receiver operating characteristic curve, sensitivity, specificity, and other relevant indicators. The findings will provide evidence-based insights to support the development of more accurate and effective ARDS prediction tools. Methods We performed a search across 6 electronic databases for studies developing ML predictive models for ARDS, with a cutoff date of December 29, 2024. The risk of bias in these models was evaluated using the Prediction model Risk of Bias Assessment Tool. Meta-analyses and investigations into heterogeneity were carried out using Meta-DiSc software (version 1.4), developed by the Ramón y Cajal Hospital’s Clinical Biostatistics team in Madrid, Spain. Furthermore, sensitivity, subgroup, and meta-regression analyses were used to explore the sources of heterogeneity more comprehensively. Results ML models achieved a pooled area under the receiver operating characteristic curve of 0.7407 for ARDS. The additional metrics were as follows: sensitivity was 0.67 (95% CI 0.66-0.67; P<.001; I²=97.1%), specificity was 0.68 (95% CI 0.67-0.68; P<.001; I²=98.5%), the diagnostic odds ratio was 6.26 (95% CI 4.93-7.94; P<.001; I²=95.3%), the positive likelihood ratio was 2.80 (95% CI 2.46-3.19; P<.001; I²=97.3%), and the negative likelihood ratio was 0.51 (95% CI 0.46-0.57; P<.001; I²=93.6%). Conclusions This study evaluates prediction models constructed using various ML algorithms, with results showing that ML demonstrates high performance in ARDS prediction. However, many of the existing models still have limitations. During model development, it is essential to focus on model quality, including reducing bias risk, designing appropriate sample sizes, conducting external validation, and ensuring model interpretability. Additionally, challenges such as physician trust and the need for prospective validation must also be addressed. Future research should standardize model development, optimize model performance, and explore how to better integrate predictive models into clinical practice to improve ARDS diagnosis and risk stratification. Trial Registration PROSPERO CRD42024529403; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024529403

Fifty years after the first description of acute respiratory distress syndrome (ARDS), none of the many positive drug studies in animal models have been confirmed in clinical trials and translated into clinical practice. This bleak outcome of so many animal experiments shows how difficult it is to model ARDS. Lungs from patients are characterized by hyperinflammation, permeability edema, and hypoxemia; accordingly, this is what most models aim to reproduce. However, in animal models it is very easy to cause inflammation in the lungs, but difficult to cause hypoxemia. Often – and not unlike in patients – models with hypoxemia are accompanied by cardiovascular failure that necessitates fluid support and ventilation, raising the question as to the role of intensive care measures in models of ARDS. In our opinion, there are two major arguments in favor of modelling intensive care medicine in models of ARDS: (1) preventing death from shock; and (2) modelling ventilation and other ICU measures as a second hit. The preferable predictive endpoints in any model of ARDS remain unclear. At present, the best recommendation is to use endpoints that can be compared across studies (i.e. PaO2/FiO2 ratio, compliance, wet-to-dry weight ratio) rather than percentage data. Another important and often overlooked issue is the fact that the thermoneutral environmental temperatures for mice and rats are 30℃ and 28℃, respectively; thus, at room temperature (20–22℃) they suffer from cold stress with the associated significant metabolic changes. While, by definition, any model is an abstraction, we suggest that clinically relevant models of ARDS will have to closer recapitulate important properties of the disease while taking into account species-specific confounders.

Background Extracorporeal Membrane Oxygenation (ECMO) therapy for respiratory failure is an increasingly popular modality of support. Patient selection is an important aspect of outcome success. This review assesses the efficacy of the popular prognostic tools Respiratory ECMO Survival Prediction Score (RESP) and Predicting Death for Severe ARDS on VV-ECMO score (PRESERVE) for ECMO patient selection. Methods A literature search was performed. Six publications were found to match the specified selection criteria. These publications were assessed and compared using the area under the receiver operating characteristic (AUROC) curve statistical method to ascertain the discriminatory ability of the models to predict treatment outcome. Results Six articles were included in this review from 306 screened, of which all were retrospective cohort studies. Data was generated over a period of 3–9 years from 13 referring hospitals. Studies consisted of 467 male and 221 female (30 unknown) participants in total with a high heterogeneity. The PRESERVE prognostic model was found to have a higher AUROC score than the RESP model, however both models were found to be sub-optimal in their discriminatory ability. A high chance of bias was seen across all included studies. Conclusion It was the findings of this review, indicated by analysis using the AUROC measures, that the prognostic model PRESERVE performed better than RESP for predicting post ECMO therapy outcomes, for patients presenting with Acute Respiratory Distress Syndrome within their respective validated time frames, i.e., RESP at Intensive care unit (ICU) discharge and PRESERVE at 6 months post ICU discharge. However, It was recognized that comparator groups were small thereby introducing bias into the study. Further prospective, randomized studies would be necessary to effectively assess the utility of these predictive survival scores.

OBJECTIVES: To assess the value of machine learning approaches in the development of a multivariable model for early prediction of ICU death in patients with acute respiratory distress syndrome (ARDS). DESIGN: A development, testing, and external validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: A total of 1,303 patients with moderate-to-severe ARDS managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed and tested prediction models in 1,000 ARDS patients. We performed logistic regression analysis following variable selection by a genetic algorithm, random forest and extreme gradient boosting machine learning techniques. Potential predictors included demographics, comorbidities, ventilatory and oxygenation descriptors, and extrapulmonary organ failures. Risk modeling identified some major prognostic factors for ICU mortality, including age, cancer, immunosuppression, Pao2/Fio2, inspiratory plateau pressure, and number of extrapulmonary organ failures. Together, these characteristics contained most of the prognostic information in the first 24 hours to predict ICU mortality. Performance with machine learning methods was similar to logistic regression (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.82–0.91). External validation in an independent cohort of 303 ARDS patients confirmed that the performance of the model was similar to a logistic regression model (AUC, 0.91; 95% CI, 0.87–0.94). CONCLUSIONS: Both machine learning and traditional methods lead to promising models to predict ICU death in moderate/severe ARDS patients. More research is needed to identify markers for severity beyond clinical determinants, such as demographics, comorbidities, lung mechanics, oxygenation, and extrapulmonary organ failure to guide patient management.

Background Early recognition of high-risk-patients with acute respiratory distress syndrome (ARDS) might improve their outcome by less protracted allocation to intensified therapy including extracorporeal membrane oxygenation (ECMO). Among numerous predictors and classifications, the American European Consensus Conferenece (AECC)- and Berlin-definitions as well as the oxygenation index (OI) and the Murray-/Lung Injury Score are the most common. Most studies compared the prediction of mortality by these parameters on the day of intubation and/or diagnosis of ARDS. However, only few studies investigated prediction over time, in particular for more than three days. Objective Therefore, our study aimed at characterization of the best predictor and the best day(s) to predict 28-days-mortality within four days after intubation of patients with ARDS. Methods In 100 consecutive patients with ARDS severity according to OI (mean airway pressure*FiO2/paO2), modified Murray-score without radiological points (Murray_mod), AECC- and Berlin-definition, were daily documented for four days after intubation. In the subgroup of 49 patients with transpulmonary thermodilution (TPTD) monitoring (PiCCO), extravascular lung water index (EVLWI) was measured daily. Primary endpoint Prediction of 28-days-mortality (Area under the receiver-operating-characteristic curve (ROC-AUC)); IBM SPSS 26. Results In the totality of patients the best prediction of 28-days-mortality was found on day-1 and day-2 (mean ROC-AUCs for all predictors/scores: 0.632 and 0.620). OI was the best predictor among the ARDS-scores (AUC=0.689 on day-1; 4-day-mean AUC = 0.625). AECC and Murray_mod had 4-day-means AUCs below 0.6. Among the 49 patients with TPTD, EVLWI (4-day-mean AUC=0.696) and OI (4-day-mean AUC=0.695) were the best predictors. AUCs were 0.789 for OI on day-1, and 0.786 for EVLWI on day-2. In binary regression analysis of patients with TPTD, EVLWI (B=-0.105; Wald=7.294; p=0.007) and OI (B=0.124; Wald=7.435; p=0.006) were independently associated with 28-days-mortality. Combining of EVLWI and OI provided ROC-AUCs of 0.801 (day-1) and 0.824 (day-2). Among the totality of patients, the use of TPTD-monitoring „per se“ and a lower SOFA-score were independently associated with a lower 28-days-mortality. Conclusions Prognosis of ARDS-patients can be estblished within two days after intubation. The best predictors were EVLWI and OI and their combination. TPTD-monitoring „per se“ was independently associated with reduced mortality.

Background Our purpose was to summarise the prognostic associations between various clinical risk factors and development of acute respiratory distress syndrome (ARDS) following traumatic injury. Methods We conducted this review in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) guidelines. We searched six databases from inception through December 2020. We included English language studies describing the clinical risk factors associated with development of post-traumatic ARDS, as defined by either the American–European Consensus Conference or Berlin definition. We pooled adjusted odds ratios for prognostic factors using the random effects method. We assessed risk of bias using the QUIPS (Quality in Prognosis Studies) tool and certainty of findings using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. Results We included 39 studies involving 5 350 927 patients. We identified the amount of crystalloid resuscitation as a potentially modifiable prognostic factor associated with development of post-traumatic ARDS (adjusted OR 1.19, 95% CI 1.15–1.24 for each additional litre of crystalloid administered within the first 6 h after injury; high certainty). Non-modifiable prognostic factors with a moderate or high certainty of association with post-traumatic ARDS included increasing age, non-Hispanic White race, blunt mechanism of injury, presence of head injury, pulmonary contusion or rib fracture and increasing chest injury severity. Conclusions We identified one important modifiable factor, the amount of crystalloid resuscitation within the first 24 h of injury, and several non-modifiable factors associated with development of post-traumatic ARDS. This information should support the judicious use of crystalloid resuscitation in trauma patients and may inform development of risk stratification tools. This systematic review identifies one important modifiable factor, the amount of crystalloid resuscitation within the first 24 h of injury, and several non-modifiable factors associated with development of post-traumatic ARDS https://bit.ly/3klhshF

To assess the performance of validated prediction models for acute respiratory distress syndrome (ARDS) by systematic review and meta‐analysis.

Introduction: Within primary ARDS, SARS-CoV-2-associated ARDS (C-ARDS) emerged in late 2019, reaching its peak during the subsequent two years. Recent efforts in ARDS research have concentrated on phenotyping this heterogeneous syndrome to enhance comprehension of its pathophysiology. Methods and Results: A retrospective study was conducted on C-ARDS patients from April 2020 to February 2021, encompassing 110 participants with a mean age of 63.2±11.92 (26-83 years). Of these, 61.2% (68) were male, and 25% (17) experienced severe ARDS, resulting in a mortality rate of 47.3% (52). Ventilation settings, arterial blood gases, and chest X-ray (CXR) were evaluated on the first day of invasive mechanical ventilation and between days two and three. CXR images were scrutinized using a convolutional neural network (CNN). A binary logistic regression model for predicting C-ARDS mortality was developed based on the most influential variables: age, PaO2/FiO2 ratio (P/F) on days one and three, CNN-extracted CXR features, and age. Initial performance assessment on test data (23 patients out of the 110) revealed an area under the receiver operating characteristic (ROC) curve of 0.862 CI (0.654-0.969). Conclusion: Integrating data available in all intensive care units enables the prediction of C-ARDS mortality by utilizing evolving P/F ratios and CXR. This approach can assist in tailoring treatment plans and initiating early discussions to escalate care and extracorporeal life support. Machine learning algorithms for imaging classification can uncover otherwise inaccessible patterns, potentially evolving into another form of ARDS phenotyping. The combined features of these algorithms and clinical variables demonstrate superior performance compared to either element alone.

Extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) has known a growing interest over the last decades with promising results during the 2009 A(H1N1) influenza epidemic. Targeting populations that can most benefit from this therapy is now of major importance.Survival has steadily improved for a decade, reaching up to 65% at hospital discharge in the most recent cohorts. However, ECMO is still marred by frequent and significant complications such as bleeding and nosocomial infections. In addition, physiological and psychological symptoms are commonly described in long-term follow-up of ECMO-treated ARDS survivors. Because this therapy is costly and exposes patients to significant complications, seven prediction models have been developed recently to help clinicians identify patients most likely to survive once ECMO has been initiated and to facilitate appropriate comparison of risk-adjusted outcomes between centres and over time. Higher age, immunocompromised status, associated extra-pulmonary organ dysfunction, low respiratory compliance and non-influenzae diagnosis seem to be the main determinants of poorer outcome.

BackgroundExtracorporeal membrane oxygenation (ECMO) is a life-saving therapy in acute respiratory distress syndrome (ARDS) patients but is associated with complications and costs. Here, we validate various scores supposed to predict mortality and develop an optimized categorical model.MethodsIn a derivation cohort, 108 ARDS patients (2010–2015) on veno-venous ECMO were retrospectively analysed to assess four established risk scores (ECMOnet-Score, RESP-Score, PRESERVE-Score, Roch-Score) for mortality prediction (receiver operating characteristic analysis) and to identify by multivariable logistic regression analysis independent variables for mortality to yield the new PRESET-Score (PREdiction of Survival on ECMO Therapy-Score). This new score was then validated both in independent internal (n = 82) and external (n = 59) cohorts.ResultsThe median (25%; 75% quartile) Sequential Organ Failure Assessment score was 14 (12; 16), Simplified Acute Physiology Score II was 62.5 (57; 72.8), median intensive care unit stay was 17 days (range 1–124), and mortality was 62%. Only the ECMOnet-Score (area under curve (AUC) 0.69) and the RESP-Score (AUC 0.64) discriminated survivors and non-survivors. Admission pHa, mean arterial pressure, lactate, platelet concentrations, and pre-ECMO hospital stay were independent predictors of death and were used to build the PRESET-Score. The score’s internal (AUC 0.845; 95% CI 0.76–0.93; p < 0.001) and external (AUC 0.70; 95% CI 0.56–0.84; p = 0.008) validation revealed excellent discrimination.ConclusionsWhile our data confirm that both the ECMOnet-Score and the RESP-Score predict mortality in ECMO-treated ARDS patients, we propose a novel model also incorporating extrapulmonary variables, the PRESET-Score. This score predicts mortality much better than previous scores and therefore is a more precise choice for decision support in ARDS patients to be placed on ECMO.

Acute respiratory distress syndrome (ARDS) is a prevalent complication among critically ill patients, constituting around 10% of intensive care unit (ICU) admissions and mortality rates ranging from 35 to 46%. Hence, early recognition and prediction of ARDS are crucial for the timely administration of targeted treatment. However, ARDS is frequently underdiagnosed or delayed, and its heterogeneity diminishes the clinical utility of ARDS biomarkers. This study aimed to observe the incidence of ARDS among high-risk patients and develop and validate an ARDS prediction model using machine learning (ML) techniques based on clinical parameters. This prospective cohort study in China was conducted on critically ill patients to derivate and validate the prediction model. The derivation cohort, consisting of 400 patients admitted to the ICU of the Peking University Third Hospital(PUTH) between December 2020 and August 2023, was separated for training and internal validation, and an external data set of 160 patients at the FU YANG People's Hospital from August 2022 to August 2023 was employed for external validation. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to screen predictor variables. Multiple ML classification models were integrated to analyze and identify the best models. Several evaluation indexes were used to compare the model performance, including the area under the receiver-operating-characteristic curve (AUC) and decision curve analysis (DCA). SHapley Additive ex Planations (SHAP) is used to interpret ML models. 400 critically ill patients were included in the analysis, with 117 developing ARDS during follow-up. The final model included gender, Lung Injury Prediction Score (LIPS), Hepatic Disease, Shock, and combined Lung Contusion. Based on the AUC and DCA in the validation group, the logistic model demonstrated excellent performance, achieving an AUC of 0.836 (95% CI: 0.762–0.910). For external validation, comprising 160 patients, 44 of whom developed ARDS, the AUC was 0.799 (95% CI: 0.723–0.875), significantly outperforming the LIPS score alone. Combining the LIPS score with other clinical parameters in a logistic regression model provides a more accurate, clinically applicable, and user-friendly ARDS prediction tool than the LIPS score alone.

Acute respiratory distress syndrome (ARDS) is a devastating critical care syndrome with significant morbidity and mortality. The objective of this study was to evaluate the predictive values of dynamic clinical indices by developing machine-learning (ML) models for early and accurate clinical assessment of the disease prognosis of ARDS. We conducted a retrospective observational study by applying dynamic clinical data collected in the ARDSNet FACTT Trial (n = 1000) to ML-based algorithms for predicting mortality. In order to compare the significance of clinical features dynamically, we further applied the random forest (RF) model to nine selected clinical parameters acquired at baseline and day 3 independently. An RF model trained using clinical data collected at day 3 showed improved performance and prognostication efficacy (area under the curve [AUC]: 0.84, 95% CI: 0.78–0.89) compared to baseline with an AUC value of 0.72 (95% CI: 0.65–0.78). Mean airway pressure (MAP), bicarbonate, age, platelet count, albumin, heart rate, and glucose were the most significant clinical indicators associated with mortality at day 3. Thus, clinical features collected early (day 3) improved performance of integrative ML models with better prognostication for mortality. Among these, MAP represented the most important feature for ARDS patients’ early risk stratification.

The application of artificial intelligence (AI) in predicting the mortality of acute respiratory distress syndrome (ARDS) has garnered significant attention. However, there is still a lack of evidence-based support for its specific diagnostic performance. Thus, this systematic review and meta-analysis was conducted to evaluate the effectiveness of AI algorithms in predicting ARDS mortality. We conducted a comprehensive electronic search across Web of Science, Embase, PubMed, Scopus, and EBSCO databases up to April 28, 2024. The QUADAS-2 tool was used to assess the risk of bias in the included articles. A bivariate mixed-effects model was applied for the meta-analysis. Sensitivity analysis, meta-regression analysis, and tests for heterogeneity were also performed. Eight studies were included in the analysis. The sensitivity, specificity, and summarized receiver operating characteristic (SROC) of the AI-based model in the validation set were 0.89 (95% CI 0.79–0.95), 0.72 (95% CI 0.65–0.78), and 0.84 (95% CI 0.80–0.87), respectively. For the logistic regression (LR) model, the sensitivity, specificity, and SROC were 0.78 (95% CI 0.74–0.82), 0.68 (95% CI 0.60–0.76), and 0.81 (95% CI 0.77–0.84). The AI model demonstrated superior predictive accuracy compared to the LR model. Notably, the predictive model performed better in patients with moderate to severe ARDS (SAUC: 0.84 [95% CI 0.80–0.87] vs. 0.81 [95% CI 0.77–0.84]). The AI algorithms showed superior performance in predicting the mortality of ARDS patients and demonstrated strong potential for clinical application. Additionally, we found that for ARDS, a highly heterogeneous condition, the accuracy of the model is influenced by the severity of the disease.

… We validated a mortality prediction model for ARDS that … model might have value for prognostic enrichment in a clinical … However, our study has some limitations. First, in two of the …

The interrelationship of sepsis and acute lung injury is complex. The development of signs of systemic inflammation due to infection, sepsis, is the most common cause of acute lung injury (ALI) accounting for 40-50% of all cases (1, 2). The subset of ALI victims with the most severe oxygenation abnormalities are said to have acute respiratory distress syndrome (ARDS). A reciprocal relationship exists in that the lung is the most commonly identified site of infection leading to the development of sepsis (3).

Definitive evidence to settle the important clinical controversies we debated in this Journal Conference are not yet available. More randomized controlled trials are clearly needed for all of the topics presented. Additionally, neonatal and pediatric data are clearly lacking on most of these questions. The key points in many of the conversations on these controversial topics focused on the balance between efficacy and safety. When safety data exist without efficacy data, the uncontrolled variables often become the knowledge, experience, and support available in an individual intensive care unit. “New” therapies have the potential to help many patients but also have the potential to do great harm if clinicians do not follow standard guidelines and/or do not have the knowledge to use the therapy appropriately. It is clear that some current standards of care will be overthrown by future data while others will be finally substantiated. This Journal Conference queried the status quo to better enable clinicians to make informed decisions in the care of their critically ill patients.

Background: Corticosteroid usage in acute respiratory distress syndrome (ARDS) remains controversial. We aim to explore the correlation between the different doses of corticosteroid administration and the prognosis of ARDS. Methods: All patients were diagnosed with ARDS on initial hospital admission and received systemic corticosteroid treatment for ARDS. The main outcomes were the effects of corticosteroid treatment on clinical parameters and the mortality of ARDS patients. Secondary outcomes were factors associated with the mortality of ARDS patients. Results: 105 ARDS patients were included in this study. Corticosteroid treatment markedly decreased serum interleukin-18 (IL-18) level (424.0 ± 32.19 vs. 290.2 ± 17.14; p = 0.0003) and improved arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) (174.10 ± 65.28 vs. 255.42 ± 92.49; p < 0.0001). The acute physiology and chronic health evaluation (APACHE II) score (16.15 ± 4.41 vs. 14.88 ± 4.57, p = 0.042) decreased significantly on the seventh day after systemic corticosteroid treatment. Interestingly, the serum IL-18 decreased significantly (304.52 ± 286.00 vs. 85.85 ± 97.22, p < 0.0001), whereas the improvement of PaO2/FiO2 (24.78 ± 35.03 vs. 97.17 ± 44.82, p < 0.001) was inconspicuous after systemic corticosteroid treatment for non-survival patients, compared with survival patients. Furthermore, the receiver operating characteristic (ROC) model revealed, when equivalent methylprednisolone usage was 146.5 mg/d, it had the best sensitivity and specificity to predict the death of ARDS. Survival analysis by Kaplan–Meier curves presented the higher 45-day mortality in high-dose corticosteroid treatment group (logrank test p < 0.0001). Multivariate Cox regression analyses demonstrated that serum IL-18 level, APACHE II score, D-dimer, and high-dose corticosteroid treatment were associated with the death of ARDS. Conclusion: Appropriate dose of corticosteroids may be beneficial for ARDS patients through improving the oxygenation and moderately inhibiting inflammatory response. The benefits and risks should be carefully weighed when using high-dose corticosteroid for ARDS. Trial registration: This work was registered in ClinicalTrials.gov. Name of the registry: Corticosteroid Treatment for Acute Respiratory Distress Syndrome. Trial registration number: NCT02819453. URL of trial registry record: https://register.clinicaltrials.gov.

The acute respiratory distress syndrome is a common, devastating clinical syndrome of acute lung injury that affects both medical and surgical patients. Since the last review of this syndrome appeared in the Journal, 1 more uniform definitions have been devised and important advances have occurred in the understanding of the epidemiology, natural history, and pathogenesis of the disease, leading to the design and testing of new treatment strategies. This article provides an overview of the definitions, clinical features, and epidemiology of the acute respiratory distress syndrome and discusses advances in the areas of pathogenesis, resolution, and treatment.Historical Perspective and Definitions . . .

The acute respiratory distress syndrome (ARDS) is a complex disorder of heterogeneous etiologies characterized by a consistent, recognizable pattern of lung injury. Extensive epidemiologic studies and clinical intervention trials have been conducted to address the high mortality of this disorder and have provided significant insight into the complexity of studying new therapies for this condition. The existing clinical investigations in ARDS will be highlighted in this review. The limitations to current definitions, patient selection, and outcome assessment will be considered. While significant attention has been focused on the parenchymal injury that characterizes this disorder and the clinical support of gas exchange function, relatively limited focus has been directed to hemodynamic and pulmonary vascular dysfunction equally prominent in the disease. The limited available clinical information in this area will also be reviewed. The current standards for cardiopulmonary management of the condition will be outlined. Current gaps in our understanding of the clinical condition will be highlighted with the expectation that continued progress will contribute to a decline in disease mortality.

… Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse …

We provide an evidence-based approach to managing patients with acute lung injury and acute respiratory distress syndrome (ARDS). We searched MEDLINE and the Cumulative Index to Nursing and Allied Health for randomized trials evaluating lung-protective ventilation strategies, inhaled nitric oxide, prone positioning, and late-phase corticosteroids for managing these patients, and for additional literature related to long-term follow-up of ARDS survivors. The results of our review suggest that pressure- and volume-limited ventilation, according to the ARDS Network protocol, can reduce mortality for patients with acute lung injury, and so may an "open lung" approach to mechanical ventilation. Those 2 strategies are currently being compared in 2 multicenter randomized trials. Although both inhaled nitric oxide therapy and prone positioning can produce dramatic acute improvements in oxygenation for some patients, there is no evidence that these interventions can benefit patients with respect to patient-important outcomes. Therefore it is unreasonable to be dogmatic about the role of inhaled nitric oxide and prone positioning in ARDS. The role of corticosteroids in the late phase of ARDS is unclear and remains a very important unanswered question. With respect to long-term follow-up, we found that pulmonary dysfunction is probably not a major source of morbidity for ARDS survivors, whereas neuropsychological dysfunction is prominent. Ongoing research may suggest interventions to improve the outcome of ARDS and of critical illness in general.

Objective: Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome whose diagnosis and therapy are still in question. The aim of this review was to discuss the current challenge for the diagnosis and treatment of ARDS. Data Sources: Data sources were the published articles in English through December 2017 in PubMed using the following key words: “acute respiratory distress syndrome,” “definition”, “diagnosis,” “therapy,” “lung protective strategy,” “right ventricular dysfunction,” and “molecular mechanism.” Study Selection: The selection of studies focused on both preclinical studies and clinical studies of therapy of ARDS. Results: The incidence of ARDS is still high, and ARDS causes high intensive care units admissions and high mortality. The Berlin Definition proposed in 2012 is still controversial owing to lack of sensitivity and specificity. ARDS is still under recognition and it is associated with high mortality. Lung protective strategies with low tidal volume (VT) and lung recruitment should consider the physiology of ARDS because ARDS presents lung inhomogeneity; the same low VT might increase local stress and strain in some patients with low compliance, and lung recruitment could injure lungs in ARDS patients with low recruitability and hemodynamic instability. Acute cor pulmonale is common in severe ARDS. ARDS itself and some treatments could worsen acute cor pulmonale. Molecular understanding of the pathogenic contributors to ARDS has improved, but the molecular-associated treatments are still under development. Conclusions: ARDS is a devastating clinical syndrome whose incidence and mortality has remained high over the past 50 years. Its definition and treatments are still confronted with challenges, and early recognition and intervention are crucial for improving the outcomes of ARDS. More clinical studies are needed to improve early diagnosis and appropriate therapy.

… Data regarding the prognosis of ARDS versus ALI are more controversial. Although several studies have shown that baseline Pao 2 /Fio 2 ratios do not predict mortality ( 10, 82, 137 ), …

The acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients and is defined by the acute onset of noncardiogenic pulmonary oedema, …

… syndrome of acute respiratory distress in adults that closely resembled respiratory distress in … They detailed the clinical course of 12 patients treated in Denver for respiratory failure that …

The definition of acute respiratory distress syndrome (ARDS) has a somewhat controversial history, with some even questioning the need for the term “ARDS.” This controversy has been amplified by the coronavirus disease (COVID-19) pandemic given the marked increase in the incidence of ARDS, the relatively new treatment modalities that do not fit neatly with the Berlin definition, and the difficulty of making the diagnosis in resource-limited settings. We propose that attempts to revise the definition of ARDS should apply the framework originally developed by psychologists and social scientists and used by other medical disciplines to generate and assess definitions of clinical syndromes that do not have gold standards. This framework is structured around measures of reliability, feasibility, and validity. Future revisions of the definition of ARDS should contain the purpose, the methodology, and the framework for empirically testing any proposed definition. Attempts to revise critical illness syndromes’ definitions usually hope to make them “better”; our recommendation is that future attempts use the same criteria used by other fields in defining what “better” means.

… Three papers stimulated much of our understanding of ventilator management of patients with the acute respiratory distress syndrome (48). The 1967 report of Ashbaugh and coworkers …

… Groundbreaking research into the pathophysiology of the adult acute respiratory distress syndrome (ARDS) and the prevention of ventilator-induced lung injury has led to dramatic …

… Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group. Am J Respir Crit Care Med 1999…