ABSTRACT
A 16-year-old castrated male shih tzu dog was brought to the emergency service because of an acute (24 h) history of gagging, coughing, and lethargy. Physical examination revealed dyspnea concurrent with diffuse, bilateral, pulmonary crackles and wheezes. Oxygen saturation, measured with a pulse oximeter, was < 95%. Thoracic radiographs revealed a multifocal alveolar pattern superimposed over a diffuse interstitial pattern with normal heart size. The dog continued to be dyspneic despite oxygen therapy. In accordance with the radiographic findings, further supportive care was recommended. Due to the unknown prognosis and financial constraints, the owner elected humane euthanasia. Necropsy confirmed a pheochromocytoma and lung changes without evidence of congestive heart failure. Findings were consistent with diffuse alveolar damage. These findings correlated with the dog's clinical diagnosis of acute respiratory distress syndrome (ARDS). No other disease processes associated with ARDS were identified. The purpose of this case report is to describe an unusual presentation of ARDS likely associated with a pheochromocytoma and confirmed by necropsy. Acute respiratory distress syndrome associated with a pheochromocytoma has been described in medical literature but has never been reported in veterinary medicine. Key clinical message: Pheochromocytomas should be added to the list of risk factors associated with ARDS in dogs. Dogs with a suspected diagnosis of pheochromocytoma whose owners elect against surgical removal should be closely monitored for an acute onset of respiratory distress, which could suggest the development of ARDS.
Syndrome de détresse respiratoire aiguë associé à un phéochromocytome chez un chien adulteUn chien shih tzu mâle castré de 16 ans a été amené aux services d'urgence en raison d'antécédents aigus (24 heures) de haut-le-coeur, de toux et de léthargie. L'examen physique a révélé une dyspnée concomitante à des crépitements et des respirations sifflantes diffuses, bilatérales et pulmonaires. La saturation en oxygène, mesurée avec un oxymètre de pouls, était < 95 %. Les radiographies thoraciques ont révélé un motif alvéolaire multifocal superposé à un motif interstitiel diffus avec une taille cardiaque normale. Le chien est resté dyspnéique malgré l'oxygénothérapie. Conformément aux résultats radiographiques, des soins de soutien supplémentaires ont été recommandés. En raison du pronostic inconnu et des contraintes financières, le propriétaire a opté pour l'euthanasie sans cruauté. La nécropsie a confirmé un phéochromocytome et des modifications pulmonaires sans signe d'insuffisance cardiaque congestive. Les résultats concordaient avec des lésions alvéolaires diffuses. Ces résultats étaient en corrélation avec le diagnostic clinique du syndrome de détresse respiratoire aiguë (ARDS) du chien. Aucun autre processus pathologique associé à l'ARDS n'a été identifié. Le but de ce rapport de cas est de décrire une présentation inhabituelle de l'ARDS probablement associée à un phéochromocytome et confirmée par la nécropsie. Le syndrome de détresse respiratoire aiguë associé à un phéochromocytome a été décrit dans la littérature médicale mais n'a jamais été rapporté en médecine vétérinaire.Message clinique clé:Les phéochromocytomes doivent être ajoutés à la liste des facteurs de risque associés à l'ARDS chez le chien. Les chiens avec un diagnostic suspecté de phéochromocytome dont les propriétaires choisissent de ne pas procéder à l'ablation chirurgicale doivent être étroitement surveillés pour détecter l'apparition aiguë d'une détresse respiratoire, ce qui pourrait suggérer le développement d'un ARDS.(Traduit par Dr Serge Messier).
Subject(s)
Adrenal Gland Neoplasms , Dog Diseases , Pheochromocytoma , Respiratory Distress Syndrome , Dogs , Animals , Pheochromocytoma/veterinary , Pheochromocytoma/complications , Male , Dog Diseases/diagnosis , Dog Diseases/etiology , Respiratory Distress Syndrome/veterinary , Respiratory Distress Syndrome/etiology , Adrenal Gland Neoplasms/veterinary , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/diagnosisABSTRACT
BACKGROUND: Trunk inclination in patients with Acute Respiratory Distress Syndrome (ARDS) in the supine position has gained scientific interest due to its effects on respiratory physiology, including mechanics, oxygenation, ventilation distribution, and efficiency. Changing from flat supine to semi-recumbent increases driving pressure due to decreased respiratory system compliance. Positional adjustments also deteriorate ventilatory efficiency for CO2 removal, particularly in COVID-19-associated ARDS (C-ARDS), indicating likely lung parenchyma overdistension. Tilting the trunk reduces chest wall compliance and, to a lesser extent, lung compliance and transpulmonary driving pressure, with significant hemodynamic and gas exchange implications. METHODS: A prospective, pilot physiological study was conducted on early ARDS patients in two ICUs at CHU Clermont-Ferrand, France. The protocol involved 30-min step gradual verticalization from a 30° semi-seated position (baseline) to different levels of inclination (0°, 30°, 60°, and 90°), before returning to the baseline position. Measurements included tidal volume, positive end-expiratory pressure (PEEP), esophageal pressures, and pulmonary artery catheter data. The primary endpoint was the variation in transpulmonary driving pressure through the verticalization procedure. RESULTS: From May 2020 through January 2021, 30 patients were included. Transpulmonary driving pressure increased slightly from baseline (median and interquartile range [IQR], 9 [5-11] cmH2O) to the 90° position (10 [7-14] cmH2O; P < 10-2 for the overall effect of position in mixed model). End-expiratory lung volume increased with verticalization, in parallel to decreases in alveolar strain and increased arterial oxygenation. Verticalization was associated with decreased cardiac output and stroke volume, and increased norepinephrine doses and serum lactate levels, prompting interruption of the procedure in two patients. There were no other adverse events such as falls or equipment accidental removals. CONCLUSIONS: Verticalization to 90° is feasible in ARDS patients, improving EELV and oxygenation up to 30°, likely due to alveolar recruitment and blood flow redistribution. However, there is a risk of overdistension and hemodynamic instability beyond 30°, necessitating individualized bed angles based on clinical situations. Trial registration ClinicalTrials.gov registration number NCT04371016 , April 24, 2020.
Subject(s)
COVID-19 , Patient Positioning , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/therapy , Prospective Studies , Male , Female , Middle Aged , Patient Positioning/methods , Pilot Projects , Aged , COVID-19/complications , COVID-19/physiopathology , COVID-19/therapy , France , Tidal Volume/physiologyABSTRACT
This study aimed to investigate the association between glucocorticoid administration and outcomes in critically ill patients with ARDS using the Medical Information Mart for Intensive Care (MIMIC)-III database. Data were collected from the MIMIC-III database, which consists of critically ill participants between 2001 and 2012 in the USA. A total of 1831 adult critically ill patients with ARDS were enrolled from the MIMIC-III database. The 60-day and in-hospital mortality, were the primary endpoints. Secondary outcomes included length of stay (LOS) in the hospital and intensive care unit (ICU), 28-day ventilator-free days, ICU mortality, and 28-day mortality. A total of 1831 patients were included in the data analysis. After propensity score (PS) matching, 464 patients diagnosed with ARDS were matched between the glucocorticoid treatment and control groups. Glucocorticoids were associated with increased in-hospital mortality [hazard ratio (HR) 1.32; 95% CI 1.01-1.71; Pâ =â .039], longer ICU stay [HR 2.25; 95% CI 0.84-3.65; Pâ =â .002], and shorter ventilation-free days at 28 days in all ARDS patients [HR -2.70; 95% CI -4.28--1.13; Pâ =â .001]. The 60-day mortality was higher in the glucocorticoid group (44.83% vs 35.34%; Pâ =â .154; HR 1.24; 95% CI 0.93-1.66). Excluding the impact of the glucocorticoid initiation time, from day 15 to day 60, mortality was significantly higher in the glucocorticoid group compared to the non-glucocorticoid group (27.16% vs 12.70%; Pâ <â .001; HR 1.75; 95% CI 1.32-2.32). Glucocorticoid administration was associated with worse 60-day and in-hospital survival, longer ICU stay, and shorter ventilator-free days on day 28 in patients with ARDS. Our findings suggest careful consideration of glucocorticoids for ARDS.
Subject(s)
Glucocorticoids , Hospital Mortality , Intensive Care Units , Length of Stay , Propensity Score , Respiratory Distress Syndrome , Humans , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Male , Female , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/drug therapy , Middle Aged , Length of Stay/statistics & numerical data , Intensive Care Units/statistics & numerical data , Aged , Databases, Factual , Critical Illness/mortality , Adult , Respiration, Artificial/statistics & numerical data , United States/epidemiologyABSTRACT
Acute respiratory distress syndrome (ARDS) occurs as an acute onset condition, and patients present with diffuse alveolar damage, refractory hypoxemia, and non-cardiac pulmonary edema. ARDS progresses through an initial exudative phase, an inflammatory phase, and a final fibrotic phase. Pirfenidone, a powerful anti-fibrotic agent, is known as an agent that inhibits the progression of fibrosis in idiopathic pulmonary fibrosis. In this study, we studied the treatment efficiency of pirfenidone on lipopolysaccharide (LPS) and bleomycin-induced ARDS using rats. The ARDS rat model was created by the intratracheal administration of 3 mg/kg LPS of and 3 mg/kg of bleomycin dissolved in 0.2 mL of normal saline. The pirfenidone treatment group was administered 100 or 200 mg/kg of pirfenidone dissolved in 0.5 mL distilled water orally 10 times every 2 days for 20 days. The administration of LPS and bleomycin intratracheally increased lung injury scores and significantly produced pro-inflammatory cytokines. ARDS induction increased the expressions of transforming growth factor (TGF)-ß1/Smad-2 signaling factors. Additionally, matrix metalloproteinase (MMP)-9/tissue inhibitor of metalloproteinase (TIMP)-1 imbalance occurred, resulting in enhanced fibrosis-related factors. Treatment with pirfenidone strongly suppressed the expressions of TGF-ß1/Smad-2 signaling factors and improved the imbalance of MMP-9/TIMP-1 compared to the untreated group. These effects led to a decrease in fibrosis factors and pro-inflammatory cytokines, promoting the recovery of damaged lung tissue. These results of this study showed that pirfenidone administration suppressed inflammation and fibrosis in the ARDS animal model. Therefore, pirfenidone can be considered a new early treatment for ARDS.
Subject(s)
Bleomycin , Lipopolysaccharides , Pyridones , Respiratory Distress Syndrome , Signal Transduction , Animals , Pyridones/pharmacology , Pyridones/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/chemically induced , Signal Transduction/drug effects , Rats , Male , Bleomycin/adverse effects , Tissue Inhibitor of Metalloproteinase-1/metabolism , Smad2 Protein/metabolism , Rats, Sprague-Dawley , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Disease Models, Animal , Matrix Metalloproteinase 9/metabolism , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta/metabolism , Lung/pathology , Lung/drug effects , Lung/metabolism , Smad Proteins/metabolismABSTRACT
In this study, we evaluated the ability of the synthetic amphipathic helical peptide (SAHP), L-37pA, which mediates pathogen recognition and innate immune responses, to treat acute respiratory distress syndrome (ARDS) accompanied by diffuse alveolar damage (DAD) and chronic pulmonary fibrosis (PF). For the modeling of ARDS/DAD, male ICR mice were used. Intrabronchial instillation (IB) of 200 µL of inflammatory agents was performed by an intravenous catheter 20 G into the left lung lobe only, leaving the right lobe unaffected. Intravenous injections (IVs) of L-37pA, dexamethasone (DEX) and physiological saline (saline) were used as therapies for ARDS/DAD. L37pA inhibited the circulating levels of inflammatory cytokines, such as IL-8, TNFα, IL1α, IL4, IL5, IL6, IL9 and IL10, by 75-95%. In all cases, the computed tomography (CT) data indicate that L-37pA reduced lung density faster to -335 ± 23 Hounsfield units (HU) on day 7 than with DEX and saline, to -105 ± 29 HU and -23 ± 11 HU, respectively. The results of functional tests showed that L-37pA treatment 6 h after ARDS/DAD initiation resulted in a more rapid improvement in the physiological respiratory lung by 30-45% functions compared with the comparison drugs. Our data suggest that synthetic amphipathic helical peptide L-37pA blocked a cytokine storm, inhibited acute and chronic pulmonary inflammation, prevented fibrosis development and improved physiological respiratory lung function in the ARDS/DAD mouse model. We concluded that a therapeutic strategy using SAHPs targeting SR-B receptors is a potential novel effective treatment for inflammation-induced ARDS, DAD and lung fibrosis of various etiologies.
Subject(s)
Cytokines , Mice, Inbred ICR , Peptides , Pulmonary Fibrosis , Respiratory Distress Syndrome , Animals , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/pathology , Mice , Male , Cytokines/metabolism , Peptides/pharmacology , Peptides/chemistry , Disease Models, Animal , Lung/pathology , Lung/drug effects , Lung/metabolismABSTRACT
BACKGROUND: Ventilation management may differ between COVID-19 ARDS (COVID-ARDS) patients and patients with pre-COVID ARDS (CLASSIC-ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC-ARDS also exist in COVID-ARDS. METHODS: Individual patient data analysis of COVID-ARDS and CLASSIC-ARDS patients in six observational studies of ventilation, four in the COVID-19 pandemic and two pre-pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator-free days and alive (VFD-60) at day 60. RESULTS: This analysis included 6702 COVID-ARDS patients and 1415 CLASSIC-ARDS patients. COVID-ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60-day mortality and less VFD-60 in both groups. Higher PEEP had an association with less VFD-60, but only in COVID-ARDS patients. CONCLUSIONS: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID-ARDS and CLASSIC-ARDS. TRIAL REGISTRATION: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022.
Subject(s)
COVID-19 , Pneumonia , Respiration, Artificial , Respiratory Distress Syndrome , Adult , Aged , Female , Humans , Male , Middle Aged , COVID-19/mortality , COVID-19/therapy , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Treatment Outcome , Pneumonia/complicationsABSTRACT
BACKGROUND: This study aimed to evaluate the role of platelet count (PLT) in the prognosis of patients with acute respiratory distress syndrome (ARDS). METHODS: The data were extracted from the Medical Information Mart for Intensive Care database (version 2.2). Patients diagnosed with ARDS according to criteria from Berlin Definition and had the platelet count (PLT) measured within the first day after intensive care unit admission were analyzed. Based on PLT, ARDS patients were divided into four groups: PLT ≤ 100 × 109/L, PLT 101-200 × 109/L, PLT 201-300 × 109/L, and PLT > 300 × 109/L. The primary outcome was 28-day mortality. Survival probabilities were analyzed using Kaplan-Meier. Furthermore, the association between PLT and mortality in ARDS patients was assessed using a univariate and multivariable Cox proportional hazards model. RESULTS: Overall, the final analysis included 3,207 eligible participants with ARDS. According to the Kaplan-Meier curves for 28-day mortality of PLT, PLT ≤ 100 × 109/L was associated with a higher incidence of mortality (P = 0.001), the same trends were observed in the 60-day (P = 0.001) and 90-day mortality (P = 0.001). In the multivariate model adjusted for the potential factors, the adjusted hazard ratio at PLT 101-200 × 109/L group, PLT 201-300 × 109/L, and PLT > 300 × 109/L was 0.681 [95% confidence interval (CI): 0.576-0.805, P < 0.001], 0.733 (95% CI: 0.604-0.889, P = 0.002), and 0.787 (95% CI: 0.624-0.994, P = 0.044) compared to the reference group (PLT ≤ 100 × 109/L), respectively. Similar relationships between the PLT ≤ 100 × 109/L group and 28-day mortality were obtained in most subgroups. CONCLUSION: PLT appeared to be an independent predictor of mortality in critically ill patients with ARDS.
Subject(s)
Kaplan-Meier Estimate , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Female , Platelet Count , Male , Middle Aged , Prognosis , Aged , Retrospective Studies , Intensive Care Units/statistics & numerical data , Proportional Hazards Models , Biomarkers/blood , AdultABSTRACT
INTRODUCTION: The primary objective of this study was to evaluate the association between the U.S. Air Force Critical Care Air Transport (CCAT) provider operational experience with compliance for lung protective ventilation (LPV) volumes recommended by Acute Respiratory Distress Syndrome Clinical Network guidelines. MATERIALS AND METHODS: We performed a retrospective cohort study of CCAT providers transporting combat casualties requiring mechanical ventilation from the Middle East to Germany from 2007 to 2012. We reviewed CCAT medical records from 2007 to 2012 for the total number of patient transports by CCAT physicians and respiratory care practitioners (RCPs). Center for Sustainment of Trauma and Readiness Skills Cincinnati process improvement questionnaire data described provider demographics and clinical backgrounds. We linked these data to patient demographics and in-flight ventilation management from a prior CCAT cohort study. Patient inclusion criteria included transport by CCAT from the Middle East to Germany for traumatic injury requiring mechanical ventilation between 2007 and 2012. We excluded patients with no documented height or tidal volume. LPV compliance was defined as tidal volumes ≤8 mL/kg of predicted body weight during en route critical care transport. We performed a logistic regression analysis. This study was reviewed and approved by the 59th Medical Wing institutional review board (IRB). RESULTS: We analyzed 491 patient transports conducted by 71 (RCPs and 84 physicians. Patients had a median age of 25 years (IQR 22-30), 98% were male, median injury severity score was 24 (IQR 17-34), and median preflight PaO2/FiO2 was 285 (IQR 220-365). Median experience was 26 missions (IQR 13-40) for RCPs and 23 missions (IQR 12-38) for physicians. All in-flight tidal volumes were LPV compliant in 58.3% of missions. Unadjusted analysis showed higher LPV compliance for RCPs with in-garrison critical care experience. Multivariate models did not find an association between missions flown and LPV compliance but did demonstrate a positive association with physician specialty of medical intensivist (OR 3.0, 95% CI 1.6-5.7) and a negative association with flights in 2008 (OR 0.4, 95% CI 0.2-0.7) for LPV compliance. CONCLUSION: No association was found between number of missions flown by CCAT providers and lung protective tidal volume compliance. Linkage of multiple data sources enabled investigation of clinical and operational currency associations with a care quality metric compliance in the combat en route care environment. Future studies should evaluate the impact of ongoing CCAT training and quality improvement interventions on LPV compliance.
Subject(s)
Air Ambulances , Respiration, Artificial , Humans , Retrospective Studies , Male , Female , Adult , Respiration, Artificial/methods , Respiration, Artificial/statistics & numerical data , Respiration, Artificial/standards , Air Ambulances/statistics & numerical data , Air Ambulances/standards , Guideline Adherence/statistics & numerical data , Guideline Adherence/standards , Critical Care/methods , Critical Care/statistics & numerical data , Critical Care/standards , Germany , Cohort Studies , Respiratory Distress Syndrome/therapy , Military Personnel/statistics & numerical data , United States , Wounds and Injuries/therapy , Surveys and QuestionnairesABSTRACT
Introduction: The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 and contributes to patient morbidity and mortality. ARDS is a heterogeneous syndrome caused by various insults, and results in acute hypoxemic respiratory failure. Patients with ARDS from COVID-19 may represent a subgroup of ARDS patients with distinct molecular profiles that drive disease outcomes. Here, we hypothesized that longitudinal transcriptomic analysis may identify distinct dynamic pathobiological pathways during COVID-19 ARDS. Methods: We identified a patient cohort from an existing ICU biorepository and established three groups for comparison: 1) patients with COVID-19 ARDS that survived hospitalization (COVID survivors, n = 4), 2) patients with COVID-19 ARDS that did not survive hospitalization (COVID non-survivors, n = 5), and 3) patients with ARDS from other causes as a control group (ARDS controls, n = 4). RNA was isolated from peripheral blood mononuclear cells (PBMCs) at 4 time points (Days 1, 3, 7, and 10 following ICU admission) and analyzed by bulk RNA sequencing. Results: We first compared transcriptomes between groups at individual timepoints and observed significant heterogeneity in differentially expressed genes (DEGs). Next, we utilized the likelihood ratio test to identify genes that exhibit different patterns of change over time between the 3 groups and identified 341 DEGs across time, including hemoglobin subunit alpha 2 (HBA1, HBA2), hemoglobin subunit beta (HBB), von Willebrand factor C and EGF domains (VWCE), and carbonic anhydrase 1 (CA1), which all demonstrated persistent upregulation in the COVID non-survivors compared to COVID survivors. Of the 341 DEGs, 314 demonstrated a similar pattern of persistent increased gene expression in COVID non-survivors compared to survivors, associated with canonical pathways of iron homeostasis signaling, erythrocyte interaction with oxygen and carbon dioxide, erythropoietin signaling, heme biosynthesis, metabolism of porphyrins, and iron uptake and transport. Discussion: These findings describe significant differences in gene regulation during patient ICU course between survivors and non-survivors of COVID-19 ARDS. We identified multiple pathways that suggest heme and red blood cell metabolism contribute to disease outcomes. This approach is generalizable to larger cohorts and supports an approach of longitudinal sampling in ARDS molecular profiling studies, which may identify novel targetable pathways of injury and resolution.
Subject(s)
COVID-19 , Erythrocytes , Gene Expression Profiling , Homeostasis , Iron , Respiratory Distress Syndrome , SARS-CoV-2 , Transcriptome , Humans , COVID-19/genetics , COVID-19/blood , Male , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/blood , Middle Aged , SARS-CoV-2/physiology , Female , Iron/metabolism , Erythrocytes/metabolism , Aged , Longitudinal StudiesABSTRACT
BACKGROUND: Acute respiratory distress syndrome (ARDS) after cardiac surgery is a severe respiratory complication with high mortality and morbidity. Traditional clinical approaches may lead to under recognition of this heterogeneous syndrome, potentially resulting in diagnosis delay. This study aims to develop and external validate seven machine learning (ML) models, trained on electronic health records data, for predicting ARDS after cardiac surgery. METHODS: This multicenter, observational cohort study included patients who underwent cardiac surgery in the training and testing cohorts (data from Nanjing First Hospital), as well as those patients who had cardiac surgery in a validation cohort (data from Shanghai General Hospital). The number of important features was determined using the sliding windows sequential forward feature selection method (SWSFS). We developed a set of tree-based ML models, including Decision Tree, GBDT, AdaBoost, XGBoost, LightGBM, Random Forest, and Deep Forest. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and Brier score. The SHapley Additive exPlanation (SHAP) techinque was employed to interpret the ML model. Furthermore, a comparison was made between the ML models and traditional scoring systems. ARDS is defined according to the Berlin definition. RESULTS: A total of 1996 patients who had cardiac surgery were included in the study. The top five important features identified by the SWSFS were chronic obstructive pulmonary disease, preoperative albumin, central venous pressure_T4, cardiopulmonary bypass time, and left ventricular ejection fraction. Among the seven ML models, Deep Forest demonstrated the best performance, with an AUC of 0.882 and a Brier score of 0.809 in the validation cohort. Notably, the SHAP values effectively illustrated the contribution of the 13 features attributed to the model output and the individual feature's effect on model prediction. In addition, the ensemble ML models demonstrated better performance than the other six traditional scoring systems. CONCLUSIONS: Our study identified 13 important features and provided multiple ML models to enhance the risk stratification for ARDS after cardiac surgery. Using these predictors and ML models might provide a basis for early diagnostic and preventive strategies in the perioperative management of ARDS patients.
Subject(s)
Cardiac Surgical Procedures , Machine Learning , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/etiology , Male , Female , Middle Aged , Cohort Studies , Cardiac Surgical Procedures/adverse effects , Aged , ROC Curve , Area Under CurveABSTRACT
INTRODUCTION: ARDS (acute respiratory distress syndrome) is the most severe form of acute hypoxic respiratory failure. Most studies related to ARDS have excluded patients with hematologic diseases, let alone allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Numerous patients experiencing severe hypoxic respiratory failure do not meet the Berlin definition due to the limitations of diagnosis and treatment. A new definition of ARDS, remove some diagnosis restrictions, was proposed in 2023. Based on the 2023 new definition of ARDS, we investigated the clinical features of ARDS in allo-HSCT recipients and reported risk factors for in-hospital mortality in allo-HSCT recipients defined by the Berlin definition and the new definition of ARDS respectively. METHODS: From Jan 2016 to Dec 2020, 135 allo-HSCT recipients identified with the new definition and 87 identified with the Berlin definition at three teaching hospitals were retrospectively included in this study. Variables (demographic information, characteristics of hematologic disease and ARDS episode, laboratory tests and SOFA score) with P < 0.05 in univariate logistic regression analysis were included in multivariate stepwise logistic regression analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. RESULTS: Under the new definition, SOFA score (OR = 1.351, 95% CI: 1.146-1.593, P < 0.01) were found as an independent risk factor for in-hospital mortality in ARDS after allo-HSCT, while SpO2/FiO2 (OR = 0.984, 95% CI: 0.972-0.996, P < 0.01) was a protective factor. The infusion of peripheral-derived stem cells was found to be a protective factor against in-hospital mortality in post-transplantation ARDS compared with the infusion of bone marrow-derived stem cells (OR = 0.726, 95% CI: 0.164-3.221, P = 0.04). Under the Berlin definition, PaO2/FiO2 (OR = 0.977, 95% CI: 0.961-0.993, P = 0.01, lactate (OR = 7.337, 95% CI: 1.313-40.989, P < 0.01) and AST (OR = 1.165, 95% CI: 1.072-1.265, P < 0.01) were independently associated with in-hospital mortality. CONCLUSION: These prognostic risk factors we found in allo-HSCT recipients may contribute to closer monitoring and ARDS prevention strategies. These findings require confirmation in prospective, large sample size studies.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hospital Mortality , Respiratory Distress Syndrome , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Retrospective Studies , Female , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Middle Aged , Risk Factors , Adult , Transplantation, Homologous/adverse effects , Aged , Logistic Models , Young AdultABSTRACT
OBJECTIVE: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes. We developed a study protocol to estimate the prevalence of low tidal volume ventilation in the first 24 hours of spontaneous ventilation in patients with hypoxemic acute respiratory failure and its association with ventilator-free days and survival. METHODS: We designed a multicenter, multinational, cohort study with a 28-day follow-up that will include patients with acute respiratory failure, defined as a partial oxygen pressure/fraction of inspired oxygen ratio < 300mmHg, in transition to spontaneous ventilation in intensive care units in Latin America. RESULTS: We plan to include 422 patients in ten countries. The primary outcomes are the prevalence of low tidal volume in the first 24 hours of spontaneous ventilation and ventilator-free days on day 28. The secondary outcomes are intensive care unit and hospital mortality, incidence of asynchrony and return to controlled ventilation and sedation. CONCLUSION: In this study, we will assess the prevalence of low tidal volume during spontaneous ventilation and its association with clinical outcomes, which can inform clinical practice and future clinical trials.
Subject(s)
Intensive Care Units , Respiratory Distress Syndrome , Tidal Volume , Humans , Latin America/epidemiology , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/physiopathology , Respiratory Distress Syndrome/mortality , Respiration, Artificial , Respiratory Insufficiency/therapy , Respiratory Insufficiency/epidemiologyABSTRACT
BACKGROUND: Acute respiratory distress syndrome (ARDS), are respiratory diseases with high morbidity and mortality. Clinical trials investigating the efficacy of corticosteroids in the treatment of ARDS often yield contradictory results. We hereby conducted a systematic review and meta-analysis to investigate the efficacy of corticosteroids in ARDS management. MATERIALS AND METHODS: We conducted a search for randomized clinical trials (RCT) and observational studies that utilized corticosteroids for patients with ARDS in Web of Science, PubMed, and Embase. The primary outcome was mortality. Risk of bias was assessed using Cochrane or NOS scales. Statistical effect size was analyzed using the Mantel-Haenszel method. RESULTS: A total of 20 studies, comprising 11 observational studies and 9 RCTs, were eligible for analysis. In RCTs, corticosteroids were associated with a reduction of mortality in ARDS patients (relative risk [RR] = 0.80, 95%CI: 0.71-0.91, p = 0.001). Further subgroup analysis indicated that specific variables, such as low-dose (RR = 0.81; 95%CI: 0.67-0.98; p = 0.034), methylprednisolone (RR = 0.70; 95%CI: 0.49-0.98; p = 0.035), and dexamethasone (RR = 0.82; 95%CI: 0.69-0.98; p = 0.029) were associated with mortality among patients receiving corticosteroids. However, in observational studies, corticosteroids increased the risk of death (RR = 1.16, 95%CI: 1.04-1.29; p = 0.001). Subgroup analysis showed that the use of high-dose corticosteroids was associated with higher patient mortality (RR = 1.20; 95%CI: 1.04-1.38; p = 0.001). CONCLUSIONS: The efficacy of corticosteroids on the mortality of ARDS differed by the type and dosage of corticosteroids used, as well as the etiologies. Current data do not support routine use of corticosteroids in ARDS since protective effects were observed in RCTs but increased mortality was found in observational studies. More well designed and large clinical trials are needed to specify the favorable subgroups for corticosteroid therapy.
Corticosteroid use may reduce the risk of death in patients with acute respiratory distress syndrome (ARDS) according to randomized controlled trials.Observational studies indicate that corticosteroid use may increase the risk of death in non-COVID-19 ARDS patients but not in COVID-19 ARDS patients.Both regular and low-dose corticosteroids show benefits in reducing mortality in RCTs, but observational studies associate these doses with increased mortality.
Subject(s)
Adrenal Cortex Hormones , Dexamethasone , Observational Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/mortality , Humans , Adrenal Cortex Hormones/therapeutic use , Dexamethasone/therapeutic use , Treatment Outcome , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosageABSTRACT
Hantavirus cardiopulmonary syndrome is a severe illness transmitted by rodent excretions. We describe a case of a 24-year-old man who presented to the emergency department with cough, shortness of breath, chills, myalgias, nausea, and diarrhea. Physical examination and laboratory analysis revealed signs of respiratory distress and thrombocytopenia. The trajectory of his illness led to acute respiratory distress syndrome (ARDS) and hemodynamic instability. Serum testing was positive for hantavirus IgM and IgG antibodies. The patient was managed with supportive care and improved. This case highlights the importance of considering hantavirus when managing patients who develop thrombocytopenia, ARDS, and hemodynamic instability in the appropriate clinical setting.
Subject(s)
Hantavirus Pulmonary Syndrome , Orthohantavirus , Humans , Male , Hantavirus Pulmonary Syndrome/diagnosis , Young Adult , Animals , Orthohantavirus/immunology , Thrombocytopenia/etiology , Respiratory Distress Syndrome/etiology , Antibodies, Viral/blood , Immunoglobulin G/blood , Mice , Immunoglobulin M/bloodABSTRACT
OBJECTIVES: To provide a comprehensive summary of the published data on cause of death in patients with acute respiratory distress syndrome (ARDS). DATA SOURCES: PubMed (January 2015 to April 2024), bibliographies of relevant articles, and ARDS Network and Prevention & Early Treatment of Acute Lung Injury (PETAL) network websites. STUDY SELECTION: Observational studies and clinical trials that reported on cause of death in greater than or equal to 30 patients with ARDS, not obtained from death certificates. Animal studies, case reports, review articles, study protocols, and studies in pediatrics were excluded. DATA EXTRACTION: Causes of death among ARDS patients who died were extracted and tabulated along with other pertinent study characteristics. DATA SYNTHESIS: We identified 15 observational studies (nine non-COVID ARDS, five COVID-related ARDS; one both) and five clinical trials (all non-COVID ARDS). Mutually exclusive prespecified categories were used for recording the cause of death in only eight studies although studies differed in the categories included and their definitions. When multiple organ failure was a predetermined category, it was the most common cause of death recorded (~50% of deaths), followed by respiratory causes with proportions varying from 16% to 42% depending on nomenclature (e.g., refractory hypoxemia, pulmonary causes) and definitions. However, the largest observational study in non-COVID ARDS (964 deaths), did not include multiple organ failure as a predetermined category, and found that pulmonary failure (42%) and cardiac failure (37%) were the most common causes of death. In COVID-related ARDS observational studies, pulmonary reasons were the most reported cause of death (up to 88%). CONCLUSIONS: Few studies have reported cause of death in patients with ARDS. In those that do, cause of death categories and definitions used are heterogeneous. Further research is needed to see whether a more rigorous and unified approach to assigning and reporting cause of death in ARDS would help identify more relevant endpoints for the assessment of targeted treatments in clinical trials.
Subject(s)
Cause of Death , Respiratory Distress Syndrome , Humans , Respiratory Distress Syndrome/mortality , COVID-19/mortality , COVID-19/complications , Observational Studies as Topic , Multiple Organ Failure/mortality , SARS-CoV-2ABSTRACT
Type 2 alveolar epithelial (AT2) cells of the lung are fundamental in regulating alveolar inflammation in response to injury. Impaired mitochondrial long-chain fatty acid ß-oxidation (mtLCFAO) in AT2 cells is assumed to aggravate alveolar inflammation in acute lung injury (ALI), yet the importance of mtLCFAO to AT2 cell function needs to be defined. Here we show that expression of carnitine palmitoyltransferase 1a (CPT1a), a mtLCFAO rate limiting enzyme, in AT2 cells is significantly decreased in acute respiratory distress syndrome (ARDS). In mice, Cpt1a deletion in AT2 cells impairs mtLCFAO without reducing ATP production and alters surfactant phospholipid abundance in the alveoli. Impairing mtLCFAO in AT2 cells via deleting either Cpt1a or Acadl (acyl-CoA dehydrogenase long chain) restricts alveolar inflammation in ALI by hindering the production of the neutrophilic chemokine CXCL2 from AT2 cells. This study thus highlights mtLCFAO as immunometabolism to injury in AT2 cells and suggests impaired mtLCFAO in AT2 cells as an anti-inflammatory response in ARDS.
Subject(s)
Acute Lung Injury , Alveolar Epithelial Cells , Carnitine O-Palmitoyltransferase , Fatty Acids , Mitochondria , Oxidation-Reduction , Respiratory Distress Syndrome , Animals , Carnitine O-Palmitoyltransferase/metabolism , Carnitine O-Palmitoyltransferase/genetics , Mitochondria/metabolism , Alveolar Epithelial Cells/metabolism , Fatty Acids/metabolism , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Acute Lung Injury/immunology , Acute Lung Injury/genetics , Mice , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/genetics , Male , Humans , Chemokine CXCL2/metabolism , Chemokine CXCL2/genetics , Mice, Inbred C57BL , Neutrophils/immunology , Neutrophils/metabolism , Mice, Knockout , Acyl-CoA Dehydrogenase, Long-Chain/metabolism , Acyl-CoA Dehydrogenase, Long-Chain/genetics , Inflammation/metabolism , Inflammation/pathology , Pulmonary Alveoli/metabolism , Pulmonary Alveoli/pathology , Pulmonary Alveoli/immunology , Adenosine Triphosphate/metabolism , Pneumonia/metabolism , Pneumonia/immunology , Pneumonia/pathology , Pneumonia/geneticsABSTRACT
Objective: Sepsis-induced acute respiratory distress syndrome (ARDS) is an independent risk factor for mortality in critically ill septic patients. However, effective therapeutic targets are still unavailable due to the lack of understanding of its unclear pathogenesis. With increasing understanding in the roles of circulating histones and endothelial dysfunction in sepsis, we aimed to investigate the mechanism of histone-induced endothelial dysfunction leading to sepsis-induced ARDS and to provide experimental support for histone-targeted treatment of sepsis-induced ARDS. Methods: First of all, in vitro experiments were conducted. Human umbilical vein endothelial cells (HUVEC) were stimulated with gradient concentrations of histones to explore for the optimal stimulation concentration in vitro. Then, HUVEC were exposed to histones at an optimal concentration with or without resatorvid (TAK-242), a selective inhibitor of Toll-like receptor 4 (TLR4), for 24 hours for modeling. The cells were divided into 4 groups: 1) the blank control group, 2) the blank control+TAK-242 intervention group, 3) the histone stimulation group, and 4) the histone+TAK-242 intervention group. HUVEC apoptosis was determined by flow cytometry, VE-Cadherin expression in endothelial cells was determined by Western blot, and the integrity of adhesion connections between endothelial cells was evaluated with confocal fluorescence microscopic images. Male C57BL/6 mice aged 6-8 weeks and weighing 22-25 g were used for the in vivo experiment. Then, the mice were given cecal ligation and puncture (CLP) as well as histone injection at 50 mg/kg via the tail vein for sepsis modeling. The experimental animals were divided into 6 groups: 1) the blank control group, 2) the blank control+TAK-242 intervention group, 3) the CLP model group, 4) the CLP+TAK-242 intervention group, 5) the histone model group, and 6) the histone+TAK-242 intervention group. After 24 h, the concentrations of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined using ELISA kits. Western blot was performed to determine the expression of vascular endothelial (VE)-cadherin in the lung tissue. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the lung tissue of the mice. Evans Blue was injected via the tail vein 30 min before the mice were sacrificed. Lung tissue was collected after the mice were sacrificed. Then, the concentrations of Evans blue dye per unit mass in the lung tissue from mice of different groups were evaluated, the rates of pulmonary endothelial leakage were calculated, and the integrity of the pulmonary endothelial barrier was evaluated. Results: The results of the in vitro experiment showed that, compared with those of the control group, HUVEC apoptosis was significantly increased under histone stimulation (P<0.05), the expression of VE-cadherin was decreased (P<0.05), and the integrity of adherens junctions between endothelial cells was damaged. TAK-242 can significantly inhibit histone-induced HUVEC apoptosis and VE-cadherin expression reduction and maintain the integrity of adherens junctions between endothelial cells. According to the findings from the in vivo experiments, in mice with CLP-induced and histone-induced sepsis, TAK-242 effectively alleviated the increase in serum concentrations of IL-6 and TNF-α, reduced the downregulation of VE-cadherin expression in the lung tissue (P<0.05), decreased endothelial permeability of the lung vessels, and improved pathological injury in the lung tissue. Conclusion: By binding to TLR-4, histone decreases VE-cadherin expression on the surface of vascular endothelial cells, disrupts the integrity of intercellular adherens junctions, and triggers pathological damage to lung tissue. Using TLR-4 inhibitors can prevent sepsis-induced ARDS in histone-induced sepsis.
Subject(s)
Apoptosis , Histones , Human Umbilical Vein Endothelial Cells , Mice, Inbred C57BL , Respiratory Distress Syndrome , Sepsis , Toll-Like Receptor 4 , Sepsis/complications , Sepsis/metabolism , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/metabolism , Humans , Animals , Mice , Histones/metabolism , Toll-Like Receptor 4/metabolism , Male , Cadherins/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Antigens, CD/metabolism , SulfonamidesABSTRACT
Introduction: Acute Respiratory Distress Syndrome (ARDS) poses a significant health challenge due to its high incidence and mortality rates. The emergence of SARS-CoV-2 has added complexity, with evidence suggesting a correlation between COVID-19 induced ARDS and post-COVID symptoms. Understanding the underlying mechanisms of ARDS in COVID-19 patients is crucial for effective clinical treatment. Method: To investigate the potential role of ferroptosis in SARS-CoV-2 induced ARDS, we conducted a comprehensive analysis using bioinformatics methods. Datasets from the Gene Expression Omnibus (GEO) were utilized, focusing on COVID-19 patients with varying ARDS severity. We employed weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and single-cell sequencing to identify key genes associated with ferroptosis in ARDS. Hub genes were validated using additional GEO datasets and cell experiment. Result: The analysis discerned 916 differentially expressed genes in moderate/severe ARDS patients compared to non-critical individuals. Weighted Gene Co-expression Network Analysis (WGCNA) unveiled two modules that exhibited a positive correlation with ARDS, subsequently leading to the identification of 15 hub genes associated with ferroptosis. Among the noteworthy hub genes were MTF1, SAT1, and TXN. Protein-protein interaction analysis, and pathway analysis further elucidated their roles. Immune infiltrating analysis highlighted associations between hub genes and immune cells. Validation in additional datasets confirmed the upregulation of MTF1, SAT1, and TXN in SARS-CoV-2-induced ARDS. This was also demonstrated by qRT-PCR results in the BEAS-2B cells vitro model, suggesting their potential as diagnostic indicators. Discussion: This study identifies MTF1, SAT1, and TXN as hub genes associated with ferroptosis in SARS-CoV-2-induced ARDS. These findings provide novel insights into the molecular mechanisms underlying ARDS in COVID-19 patients and offer potential targets for immune therapy and targeted treatment. Further experimental validation is warranted to solidify these findings and explore therapeutic interventions for ARDS in the context of COVID-19.
Subject(s)
COVID-19 , Ferroptosis , Gene Expression Profiling , Respiratory Distress Syndrome , SARS-CoV-2 , Humans , Ferroptosis/genetics , COVID-19/genetics , COVID-19/immunology , Respiratory Distress Syndrome/genetics , SARS-CoV-2/physiology , Transcriptome , Gene Regulatory Networks , Computational Biology/methodsABSTRACT
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.