Acute Respiratory Distress Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) is a major cause of acute hypoxemic respiratory failure in critically ill patients and is associated with substantial mortality. Current management is largely supportive, and no pharmacologic therapy has been shown consistently to reduce mortality in a broad population of patients with ARDS. Inflammation plays a central role in the pathogenesis of ARDS. Excessive inflammatory activation contributes to alveolar-capillary injury, impaired gas exchange, and progression of organ dysfunction. Glucocorticoids may mitigate these processes and have been associated in some studies with improved clinical outcomes, including shorter duration of mechanical ventilation. However, the effect of glucocorticoids on survival remains uncertain. ARDS is a heterogeneous syndrome with diverse etiologies, and treatment response may vary according to the underlying cause. A post hoc analysis of the Dex-ARDS trial suggested that the treatment effect of glucocorticoids may be greater in ARDS caused by pneumonia or extrapulmonary sepsis. In a cross-sectional survey of 135 patients with ARDS from 20 ICUs in China, pneumonia- and extrapulmonary sepsis-associated ARDS accounted for 77.6% of cases, indicating that these are the predominant etiologic subtypes encountered in clinical practice in China. More importantly, compared with ARDS attributable to other causes, pneumonia- and extrapulmonary sepsis-associated ARDS has been associated with higher mortality, suggesting a greater disease burden, worse prognosis, and a more urgent need for improved treatment strategies. On this basis, the present trial will enroll patients with ARDS caused by sepsis, including pneumonia and extrapulmonary sepsis. The primary hypothesis of this study is that, among patients with sepsis-associated ARDS, dexamethasone plus usual care, as compared with placebo plus usual care, will reduce 90-day all-cause mortality. We therefore designed a multicenter, randomized, double-blind, controlled trial to evaluate the clinical efficacy of dexamethasone in patients with sepsis-associated ARDS. The primary objective is to compare dexamethasone plus usual care with placebo plus usual care with respect to 90-day all-cause mortality.

This prospective, randomized crossover physiological study evaluates the effects of lateral positioning (left lateral position and right lateral position) versus the supine position on ventilation-perfusion (V/Q) matching in adult postoperative abdominal surgery participants with acute respiratory distress syndrome (ARDS). Bedside electrical impedance tomography (EIT) will be used to quantify regional ventilation and perfusion (perfusion derived from an intravenous tracer bolus administered during a brief breath-hold) and to calculate global "normal V/Q" (normal V/Q, %). Oxygenation, respiratory mechanics (when applicable), and hemodynamics will be recorded concurrently. Feasibility and safety of the positioning protocol will also be assessed.

Acute respiratory distress syndrome (ARDS) is a severe lung condition that often requires invasive mechanical ventilation in the intensive care unit. In these patients, setting the ventilator appropriately is essential to improve oxygenation while limiting ventilator-induced lung injury. One important ventilator setting is positive end-expiratory pressure (PEEP), which helps keep the lungs open. However, the optimal PEEP level may vary from one patient to another. The recruitment-to-inflation ratio (R/I ratio) is a bedside measurement used to estimate the potential for lung recruitment during a decrease in PEEP. It compares the compliance of the lung volume recruited by PEEP with the compliance of the already aerated lung. A higher R/I ratio suggests that increasing PEEP is more likely to reopen collapsed lung units, whereas a lower R/I ratio suggests limited recruitability and a higher likelihood that additional pressure would mainly distend lung areas that are already open. In clinical practice, the R/I ratio is increasingly used to guide PEEP adjustment, with the aim of improving recruitment and oxygenation while avoiding unnecessary increases in airway pressure. However, although the R/I ratio is used in routine care, there are currently no data demonstrating that this measurement is reproducible when repeated in the same patient under similar conditions. The hypothesis of this study is that the R/I ratio is reproducible when measured twice in the same patient under stable conditions, including no significant changes in ventilator settings, hemodynamic status, or ongoing treatments. This prospective, multicenter, non-interventional study will include adult ICU patients with ARDS who are receiving invasive mechanical ventilation, deep sedation, and assist-control ventilation. For each patient, airway opening pressure will be assessed, and the R/I ratio will be measured twice on the same day by a trained clinician, between 20 and 120 minutes apart, without changes in ventilator settings or treatments likely to influence the measurement. The main objective is to evaluate the within-patient reproducibility of the R/I ratio. Secondary objectives include describing changes in airway opening pressure and R/I ratio over time, assessing the reproducibility of expired tidal volume during the maneuvers, and evaluating the clinical tolerance of these ventilatory measurements. The study will include 80 patients across 4 French intensive care units. No additional intervention outside routine care will be performed. Clinical, ventilatory, and biological data already collected as part of usual care will be recorded.

While mechanical ventilation can be used to sustain life in those with lung injury, it, can further worsen lung injury or prevent lung healing resulting in high morbidity and mortality as seen in Acute Respiratory Distress Syndrome (ARDS). Using extracorporeal membrane oxygenation (ECMO), the highest level of life support also known as the heart-lung machine, investigators may minimize injury from mechanical ventilation to allow the lungs to heal; however, the optimal ventilator strategies while on ECMO are unknown. This study will evaluate personalized ventilator strategy compared to standard of care ventilation.

Acute respiratory distress syndrome (ARDS) is characterized by pathological pulmonary edema caused by direct or indirect damage to the alveolar-capillary membrane. Its management relies on etiological treatment, invasive mechanical ventilation, and the use of sedatives and neuromuscular blockers, depending on the patient's condition. Improvements in patient care have led to an improved prognosis. However, in-hospital mortality remains high (between 35% and 45%). Notably, morbidity among surviving patients is very high and is largely dominated by neuropsychological sequelae. Attention and executive function disorders, confusion, disorientation, or memory impairment are thus found in 70 to 100% of patients following ARDS. These disorders are still present in 46 to 80% of surviving patients one year after ARDS and in 20% of them five years later. Although essential to treatment, mechanical ventilation carries a risk of significant complications. Beyond the risk of infection and complications related to sedation and neuromuscular blockade, the use of mechanical ventilation is associated with a risk of ventilator-induced lung injury (VILI). The use of so-called protective ventilation reduces the risk of VILI and improves patient outcomes. However, analysis of relevant physiological parameters shows that the risk of VILI may still exist even when ventilator settings comply with recommendations and the concept of protective ventilation. Driving pressure (which represents Strain) is a good marker of VILI; it represents the distension of the lung with each breath relative to the initial lung volume. Values above 14 cmH₂O are associated with high mortality in patients with ARDS. Inspiratory transpulmonary pressure represents Stress-that is, the pressure that distends the alveoli at the end of inspiration-and is also associated with the risk of VILI. Finally, mechanical power represents the amount of energy delivered to the lung by the ventilator and has been validated as a marker of VILI. The advantage of mechanical power over the other indices described is that it incorporates all components that can lead to VILI. Among the various sources of neurological damage during ARDS, inflammatory processes appear to play a major role. Numerous inflammatory mediators (TNF-α, IL-6, IL-8, IL-1β) are secreted during ARDS, and animal studies have demonstrated a link between inflammation and hippocampal damage. Furthermore, cerebral ischemic lesions, exacerbated by systemic inflammation and endothelial activation leading to coagulation activation with thrombus formation, may also contribute to the development of cognitive impairments. In addition to the inflammatory processes associated with ARDS, mechanical ventilation itself may have a significant impact on neuroinflammatory damage. Recently, the term "ventilator-associated brain injury" (VABI) has been proposed to describe these secondary neurological lesions induced by mechanical ventilation. Studies in mouse and pig models have demonstrated a relationship between the dose and duration of VILI, apoptosis, neuroinflammation, and neuronal damage. An animal study in mice also showed an association between the duration of mechanical ventilation and the onset of cognitive impairments. During brain injury, proteins and neurotransmitters are released and serve as biomarkers of brain damage. Elevated plasma levels of S100B protein indicate astrocyte damage caused by traumatic, anoxic-ischemic, or inflammatory mechanisms. It correlates with neurological prognosis following cardiac arrest, in ischemic or hemorrhagic strokes, in neurodegenerative diseases, and in patients with traumatic brain injury. Clinical studies have shown a negative correlation between elevated S100B protein levels, the MoCA (Montreal Cognitive Assessment) score, and the MMSE (Mini-mental state evaluation ) in patients with OSA (Obstructive Sleep Apnea) or COPD (chronic obstructive pulmonary disease), respectively, indicating an association between this protein and cognitive impairment. The investigators therefore hypothesize that mechanical ventilation associated with high mechanical power is linked to a significant risk of brain injury, reflected by elevated serum S100B protein levels and the presence of neurocognitive disorders long after ARDS.

Acute respiratory distress syndrome (ARDS) is a common clinical syndrome in the ICU characterized by extremely high mortality and complex pathogenesis.At present, research on individualized treatment, phenotypic differences, and therapeutic efficacy in ARDS has become a hotspot.As characterized by syndrome differentiation, traditional Chinese medicine (TCM) treatment emphasizes interindividual heterogeneity and personalized management, which is expected to serve as a breakthrough in multi-target immune regulation for ARDS. The primary objective of the study is to investigate the effect of Xuanbai Shengmai Decoction on the prognosis of patients with ARDS in a prospective randomized controlled trial. The secondary objective is to evaluate the safety of Xuanbai Shengmai Decoction in the treatment of patients with ARDS.

Mechanical ventilation in COPD requires a good interaction Patient-Ventilator without asynchronies in order to reduce mortality. Dynamic hyperinflation with PEEPi is responsible for major asynchronies in COPD. It is supposed to be symmetrical between the 2 lungs with the same PEEPi. EIT can measure the distribution of tidal ventilation and interlung lung insufflation delay on the impedance time curve of each lung. Moreover, it is possible in intubated COPD patients to assess one lung PEEPi during low flow insufflation with pressure-EIT monitoring. This study aims to measure interlungs insufflation delay under mechanical ventilation in COPD patients

About 10% of patients admitted to the ICU suffer from ARDS, with a mortality rate of around 35-45%. The lack of therapeutic innovation in ARDS can be partly explained by the heterogeneity of patients included under this definition. A better understanding of the pathophysiological mechanisms underlying the different patient phenotypes is essential to develop new therapeutic strategies. Objectives: To characterize the inflammatory profile of patients with ARDS using circulating biomarkers and single-cell RNA sequencing of pulmonary immune cells. The investigators hypothesize that there is a correlation between the profile of serum biomarkers (inflammatory sub-phenotypes), the transcriptome of pulmonary immune cells. Briefly the experimental scheme is as follow: * Population: patients with ARDS under invasive mechanical ventilation in the ICU. * Intervention: 1. Determination of the inflammatory subphenotype on circulatory inflammatory biomarkers. 2. Characterization of inflammation by single cell RNA sequencing on lung immune cells collected on broncho-alveolar fluid.

Approximately 300,000 Hispanic individuals experience respiratory failure each year in the U.S. Hispanic patients are twice as likely to die from respiratory failure as non-Hispanic patients. There is an urgent need to identify and remediate mechanisms that increase risk of death from respiratory failure. The team's preliminary work identified two potential mechanisms: Hispanic patients with respiratory failure are more likely to be deeply sedated and less likely to receive physical therapy than non-Hispanic patients, which are both associated with mortality and poor long-term functional outcomes. The overall objective of this proposal is to improve outcomes for patients with respiratory failure through changes in intensive care unit (ICU) practice. This trial will refine and pilot an intervention to promote guideline-concordant care. The team's preliminary intervention will be iteratively refined through patient, family, and clinician engagement and piloted at two U.S. ICUs. The outcome of this study will be an intervention aimed at reducing mortality from respiratory failure.

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Cohort A: Participants will be randomized to receive either a placebo or vilobelimab. This record describes the default procedures and analyses for Cohort A. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Cohort B: Participants will be randomized to receive either a placebo or paridiprubart. This record describes the default procedures and analyses for Cohort B. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Participants will be randomized to receive either a placebo or one of the active treatments. This record describes the default procedures and analyses for all cohorts. Each specific cohort may have additional eligibility requirements, safety and efficacy procedures, or endpoints, which will be described in the corresponding intervention-specific records on clinicaltrials.gov listed below in the detailed description.

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Cohort C: Participants will be randomized to receive either a placebo or bevacizumab. This record describes the default procedures and analyses for Cohort C. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.

The purpose of this clinical trial is to determine the best initial non-invasive respiratory support (NIRS) strategy for adults who present to the emergency department with acute hypoxemic respiratory failure, a condition in which blood oxygen levels are dangerously low and require urgent treatment. This study compares two commonly used non-invasive respiratory support strategies to evaluate their effectiveness and safety, based on important patient outcomes during hospitalization, including survival, the need for invasive mechanical ventilation, and the duration of respiratory support. Participants will be randomly assigned (with an equal chance) to receive one of the following treatments: * Non-Invasive Positive Pressure Ventilation (NIPPV): Oxygen delivered under pressure through a face mask. * High-Flow Nasal Oxygen (HFNO): Oxygen delivered at high-flow through a specially designed nasal cannula placed in the nostrils. Researchers will compare the two treatment strategies using a hierarchical assessment of major pulmonary outcomes, including: * Hospital survival * Days on mechanical ventilation * Duration of non-invasive respiratory support As part of the study, researchers will collect: * Blood and urine samples * Physiologic measurements (such as chest movement measured through sensors placed on the skin) * Information from participants' medical records

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury and a major cause of Intensive Care Unit (ICU) admission worldwide. Despite a large number of randomized clinical trials, a specific and effective pharmacological approach for patients with ARDS is still lacking. Fibroproliferation is a crucial part of the host defence response, and severe fibrotic lung disease affects ARDS patients even years after acute phase resolution. Pirfenidone is an oral anti-fibrotic drug, approved and largely used for treatment of idiopathic pulmonary fibrosis (IPF). The effect of Pirfenidone in ARDS has been evaluated only in animal models. This is a randomized controlled study to evaluate for the first time the efficacy of Pirfenidone in ARDS.

This study is a prospective observational cohort study conducted planned to include 40 patients with ARDS to assess the effect of different levels of PEEP titration on VExUS score and renal outcomes in patients with Acute Respiratory Distress Syndrome.

The goal of this observational pilot study is to learn if sodium bicarbonate can be used safely and effectively as a contrast agent to map lung blood flow using electrical impedance tomography (EIT) in adults on mechanical ventilation. Electrical impedance tomography (EIT) is a bedside imaging method that uses a soft belt with small sensors around the chest to track changes in electrical signals related to breathing and blood flow. The main questions are: Does sodium bicarbonate create clear, readable lung blood flow images with EIT? Are these images similar in quality and pattern to images made with hypertonic saline (10% sodium chloride)? Is the short-term safety profile acceptable, including effects on blood pressure, heart rhythm, and blood tests? Researchers will compare two contrast agents within the same participant to see if image quality and lung blood flow patterns match: Hypertonic saline (10% sodium chloride) Sodium bicarbonate (5%) Participants will: Have an EIT belt placed around the chest during routine ICU care Pause the ventilator briefly during image capture to reduce motion Receive two small intravenous boluses through an existing central line, one of hypertonic saline and one of sodium bicarbonate, with time between doses Have routine monitoring of vital signs; blood gases and electrolytes may be checked per clinical care Be observed for any short-term side effects Findings from this study will show whether sodium bicarbonate is a practical and safe option for EIT-based lung blood flow assessment and will guide larger future studies.

Acute respiratory distress syndrome (ARDS) accounts for approximately 10% of all ICU admissions and 23% of patients requiring mechanical ventilation (MV). Despite advances in care, hospital mortality remains high, ranging from 34% in mild cases to 46% in severe ARDS. Positive-pressure MV remains the cornerstone of ARDS management. However, when excessive stress and strain are applied to the lung parenchyma, it can exacerbate lung injury, leading to ventilator-induced lung injury (VILI). VILI substantially contributes to morbidity and mortality in ARDS. Strategies that reduce tidal volume (Vt), driving pressure (ΔP, defined as plateau pressure minus PEEP), and respiratory rate (RR) can lower the mechanical power (PowerRS), i.e., the energy delivered to the lungs by the ventilator. This reduction in pulmonary stress and strain may lessen VILI and potentially improve survival. Nonetheless, reducing Vt to \<6 ml/kg in order to achieve plateau pressures \<23-25 cm H₂O, driving pressures \<9-11 cm H₂O, and RR \<15-20/min can result in severe hypercapnia. This, in turn, may increase intracranial pressure, promote pulmonary hypertension, impair myocardial contractility, reduce renal perfusion, and trigger endogenous catecholamine release. Thus, such "ultraprotective" MV strategies are not feasible for most ARDS patients managed with conventional ventilation. The neutral findings of the REST trial further suggested that low-flow extracorporeal CO₂ removal (ECCO₂R) devices may provide insufficient CO₂ clearance to enable ultraprotective ventilation while adequately controlling respiratory acidosis. Moreover, since partial lung derecruitment may occur with substantial Vt reduction, extracorporeal membrane oxygenation (ECMO) may be necessary, particularly in patients with PaO₂/FiO₂ \<120-130 at the time of Vt reduction. Therefore, respiratory extracorporeal life support (ECLS)-ranging from high-flow ECCO₂R to mid-flow venovenous ECMO (VV-ECMO)-can be employed in this setting. These modalities facilitate further reductions in ventilatory intensity while ensuring adequate oxygenation and CO₂ removal.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition with a diffuse, inflammatory form of lung injury, causing pulmonary infiltration and respiratory failure leading to poor oxygenation. It is a rapidly progressive form of respiratory failure and accounts for approximately 10% of admissions to the intensive care unit (ICU) and has a high mortality (40%) in severe cases. Globally, approximately 3 million ARDS cases are reported each year, with around 200,000 cases seen in the United States. The etiology of ARDS could be pulmonary or extra-pulmonary. Patients with ARDS have symptoms like difficulty in breathing, shortness of breath, and cyanosis, and they may require assisted breathing/ventilatory support/extracorporeal membrane oxygenation. About 25% of ARDS patients need mechanical ventilation to support breathing; however, a ventilator-induced lung injury (VILI) is known to further exacerbate ARDS in many of them. In recent decades, numerous efforts have been made to develop therapies for treating/managing ARDS. Unfortunately, they have been largely unsuccessful or inconclusive, and at present, no effective pharmacological therapy for ARDS is available. Hence, development of better therapeutics for ARDS is an unmet need. Centhaquine is a first-in-class resuscitative agent for hypovolemic shock approved for marketing in India. Centhaquine has been found to be an effective resuscitative agent in rat, rabbit, and swine models of hemorrhagic shock. Its safety and tolerability have been demonstrated in a human phase I study in 25 subjects (CTRI/2014/06/004647). Results from multicentric, randomized, double-blind, parallel, controlled clinical phase II (CTRI/2017/03/008184) and phase III (CTRI/2019/01/017196) studies conducted in India indicate that centhaquine is a novel, first-in-class, highly effective resuscitative agent for hypovolemic shock. A total of 155 patients with hypovolemic shock have been studied in the combined phase II and III trials, while a multicentric phase IV study (NCT05956418) in 400 patients with hypovolemic shock is currently being conducted in India. The outcomes of the completed trials indicate that centhaquine is safe and reduces mortality significantly (P=0.0271) compared to standard treatment of hypovolemic shock. In the phase II and III studies, ARDS and MODS were evaluated as secondary endpoints. Centhaquine provided hemodynamic stability and significantly reduced ARDS and multiple organ dysfunction score (MODS) in patients enrolled in these trials, which suggests that centhaquine has potential beyond treating hypovolemic shock and could be useful for ARDS treatment. Centhaquine is likely to provide hemodynamic stability, improve tissue oxygenation, reduce pulmonary edema, reduce ARDS score, and reduce MODS in patients with ARDS.

This multicenter, physiological, observational study hypothesizes that in moderate to severe ARDS, trunk inclination unloads the chest wall, but its impact on lung mechanics depends on PEEP levels and lung recruitability.

Acute respiratory distress syndrome (ARDS) is a serious and potentially life-threatening lung condition that can affect children. Currently, ventilator settings commonly used in treatment are based on approaches developed for adults, and it remains unclear whether these settings are equally effective for children. Because children's bodies respond differently than adults', it is important to determine the most effective ventilator strategies specifically for pediatric patients. This study will compare two different ventilator approaches in children with ARDS to identify which method provides the greatest benefit. The findings will also help inform the design of a larger study in the future.

Acute hypoxemic respiratory failure may progress to acute respiratory distress syndrome, a life-threatening condition that often requires mechanical ventilation. The optimal ventilation strategy in this patient population remains uncertain. The SVALBARD trial is a feasibility and pilot study designed to compare spontaneous versus controlled mechanical ventilation in patients with acute hypoxemia respiratory failure. The primary objective is to assess the feasibility of the study procedures and interventions, while also collecting descriptive data on key clinical variables to inform the design of a future randomized controlled trial.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. Prone position ventilation (PPV) is an evidence-based therapy that improves oxygenation and survival in patients with moderate to severe ARDS; however, outcomes remain heterogeneous. Early identification of patients at high risk of mortality after PPV may improve clinical decision-making and individualized management. This retrospective observational study aims to develop and validate a machine learning model to predict intensive care unit (ICU) mortality in ARDS patients receiving prone position ventilation. Clinical, laboratory, and treatment variables collected from ICU electronic medical records will be used to construct prediction models using multiple machine learning algorithms. The performance of these models will be evaluated and compared to identify the optimal model for mortality prediction.

The main objective is to assess the effect of increased PEEP on echo-Doppler venous congestion in ARDS patients at two PEEP levels, by grading congestion in each venous flow (suprahepatic, renal, portal) as "absent," "moderate," or "severe," and also calculating the VExUS score.

The aim of this study is to evaluate the role of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as predictors for development of ARDS in pediatric burn patients.