Related Acute Respiratory Distress Syndrome Research Articles

Echocardiographic assessment of right ventricular performance in COVID-19 related acute respiratory distress syndrome: the importance of systo-diastolic interaction.

The cardiac manifestations of COVID-19 have been described in patients with acute respiratory distress syndrome (ARDS) admitted to intensive care unit (ICU). The presence and impact of right ventricular (RV) diastolic function and performance has not been studied in this population yet. We describe the prevalence of RV diastolic dysfunction, assessed by the pulmonary valve pre-ejection A wave (PV A wave), and the RV systo-diastolic interaction, using the RV total isovolumic time (t-IVT), in COVID-19 ARDS. Prospective observational study enrolling patients with moderate to severe COVID-19 ARDS admitted to ICU who underwent a transthoracic echocardiogram within 24h of ICU admission and at least a second one during the ICU stay. Respiratory, hemodynamic and biochemistry parameters were collected. 163 patients (age 61.0 ± 9.3years, 72% males) were enrolled. 36 patients (22.1%) had RV dysfunction, 45 (27.1%) LV systolic dysfunction. 73 patients (44.7%) had PV A wave. The RV t-IVT correlated with TAPSE at ICU admission (p < 0.002; r -0.61), presence of PV A wave (p < 0.001; r 0.78), peak inspiratory pressure (PIP) (p < 0.001; r 0.42), PEEP (p < 0.001; r 0.68), dynamic driving pressure (DDP) (p < 0.001; r 0.58), and PaO2/FiO2 ratio (p < 0.01; r -0.35). The presence of PV A wave was associated with higher PIP (p < 0.001; r 0.45), higher PEEP (p < 0.001; r 0.56), higher DDP (p < 0.01, r 0.51), and lower PaO2/FiO2 ratio (p < 0.001; r -0.49). RV t-IVT and the presence of PV A wave are non-invasive means to describe a significant RV diastolic dysfunction and may be consider descriptive signs of RV performance in COVID-19 ARDS.

Oral beta-hydroxybutyrate alleviates COVID-19 related acute respiratory distress syndrome: A randomized, single-blind, placebo-controlled trial

BackgroundAcute respiratory distress syndrome (ARDS) is a lung complication of COVID-19 that requires intensive care and ventilation. Beta-hydroxybutyrate (BHB) is a ketone body that can modulate metabolism and inflammation in immune cells and lung tissues. We hypothesized that oral BHB could alleviate COVID-19 related ARDS by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. MethodsWe randomized 75 patients with mild (as per Berlin criteria) ARDS symptoms to receive oral 25 g twice daily or placebo for five days. The primary outcome was the change in pro-inflammatory cytokines (Interleukin-1β, Interleukin-6, interleukin-18, tumour necrosis factor-alpha) and anti-inflammatory cytokine (interleukin-10) from baseline to day 5. The secondary outcomes were the change in BHB levels from baseline to day 5, the number of hospitalization days, and the occurrence of adverse events. ResultsTreatment with formulated BHB resulted in a significant decrease in pro-inflammatory cytokines; Interleukin-1β (p = 0.0204), Interleukin-6 (p = 0.0309), interleukin-18 (p = 0.0116), tumour necrosis factor-alpha (p = 0.0489) and increase in interleukin-10 (p = 0.0246) compared treatment with placebo. Importantly, higher BHB levels (p = 0.0001) were observed after supplementation; additionally, patients who underwent this approach were hospitalized for fewer days. No serious adverse events were reported. ConclusionBeta-hydroxybutyrate, an oral adjunct therapy, has shown promising results in ameliorating symptoms of ARDS. This includes reduced inflammation, oxidative stress, and decreased patient fatigue levels. Further study with a large sample size is warranted to assess the potential of BHB therapy's effectiveness in reducing the development of severe illness. Clinical trial registration(http://ctri.nic.in/CTRI/2021/03/031790)

Quantitative CT scan and response to pronation in COVID-19 ARDS.

Background: The use of the prone position (PP) has been widespread during the COVID-19 pandemic. While it has demonstrated benefits, including improved oxygenation and lung aeration, the factors influencing the response in terms of gas exchange to PP remain unclear. In particular, the association between baseline quantitative Computed Tomography (qCT) scan results and gas exchange response to PP in intubated, mechanically ventilated subjects with COVID-19 ARDS is unknown. The present study aimed to compare baseline qCT results between subjects responding to PP in terms of oxygenation or carbon dioxide (CO2) clearance and those who did not.Methods: This was a single-center, retrospective observational study, including critically ill, intubated, mechanically ventilated subjects with COVID-19 related acute respiratory distress syndrome admitted to the ICUs of Niguarda Hospital between March 2020 and November 2021. Blood-gas samples were collected before and after PP. Subjects in whom the PaO2/FiO2 increase was ≥ 20 mmHg after PP were defined as Oxygen responders (Oxy-R). CO2-responders (CO2R) were defined when the ventilatory ratio (VR) decreased during PP. Automated qCT analyses were performed to obtain tissue mass and density of the lungs.Results: One hundred twenty-five subjects were enrolled, of which 116 (93%) were Oxy-R and 51 (41%) CO2R. No difference in qCT characteristics and oxygen were observed between Oxy-R and Oxygen Non Responders (Tissue mass 1532 ±396 vs. 1654 ±304 g, p= .28; density -544±109 vs. -562±58 HU, p= .42). Similar findings were observed when dividing the population according to CO2 response (Tissue mass 1551±412 vs. 1534±377 g, p= .89; density -545±123 vs. -546±94 HU, p= .99).Conclusions: Most COVID-19 related ARDS subjects improve their oxygenation at the first pronation cycle. The study suggests that baseline qCT scan data are not associated with the response to PP in oxygenation or CO2 in mechanically ventilated COVID-19 related ARDS subjects.

The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS

IntroductionEXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier.MethodsA randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria.ResultsThe mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group.ConclusionsEXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo.

Association between a low-risk COVID-19 extracorporeal membrane oxygenation criteria and mortality: A retrospective study.

Our study aimed to compare the outcomes of COVID-19 patients who met a low-risk inclusion criteria for veno-venous extra corporeal membrane oxygenation (VV ECMO) with those who did not meet criteria due to higher risk but were subsequently cannulated. This was a retrospective observational cohort study that included adult patients who were placed on VV ECMO for COVID-19 related acute respiratory distress syndrome (ARDS) at a tertiary care academic medical center. The primary outcome was the association between the low-risk criteria and mortality. The patients met the criteria if they met EOLIA severe ARDS criteria, no absolute contraindications (age > 60 years, BMI > 55 kg/m2, mechanical ventilation (MV) duration >7 days, irreversible neurologic damage, chronic lung disease, active malignancy, or advanced multiorgan dysfunction), and had three or less relative contraindications (age > 50 years, BMI > 45 kg/m2, comorbidities, MV duration > 4 days, acute kidney injury, receiving vasopressors, hospital LOS > 14 days, or COVID-19 diagnosis > 4 weeks). Sixty-five patients were included from March 2020 through March 2022. Patients were stratified into low-risk or high-risk categories. The median Sequential Organ Failure Assessment score was 7 and the median PaO2/FiO2 ratio was 44 at the time of ECMO cannulation. The in-hospital mortality was 47.8% in the low-risk group and 69.0% in the high-risk group (p = 0.096). There was not a statistically significant difference in survival between low-risk patients and high-risk patients; however, there was a trend toward higher survival in the lower-risk group.

The Risk of Pretransplant Blood Transfusion for Primary Graft Dysfunction After Lung Transplant

BackgroundPrimary graft dysfunction (PGD) is the leading cause of short- and long-term mortality associated with lung transplantation. The impact of pretransplantation blood transfusions for recipients is not fully elucidated. MethodsThis is a retrospective review of 206 consecutive lung transplantations performed at a single academic center (Northwestern University Feinberg School of Medicine, Chicago, IL) from January 2018 to July 2022. Data on patient characteristics, pretransplantation laboratory values, transfusion requirements, and intraoperative and postoperative outcomes were collected. ResultsPGD grade 3 (PGD 3) occurred in 13.2% of the cohort (n = 28). A total of 33 patients received a blood transfusion within 4 weeks, whereas 21 patients received a blood transfusion a week before their lung transplant. Pretransplantation transfusions were strongly associated with a higher incidence of PGD 3 (48.5% vs 6.9%; P < .001). There was no significant difference in 1-year survival between the pretransplantation transfused group and the nontransfused group (77.7% vs 88.0%; P = .478). The 1year survival was reduced in recipients with PGD 3 compared with recipients without PGD 3 (63.5% vs 89.9%; P = .0012). In univariate analysis, pretransplant and intratransplant predictors of PGD 3 included younger age (P < .01), pretransplant extracorporeal membrane oxygenation (ECMO) use (P < .001), higher lung allocation score (P < .001), coronavirus disease 2019 (COVID-19)–related acute respiratory distress syndrome (P < .01), blood transfusion within 4 weeks (P < .001), longer operative time (P < .001), intratransplant blood transfusion (P < .001), and intratransplant venoarterial ECMO use (P < .001). ConclusionsPretransplantation blood transfusions could be associated with a higher rate of PGD. The findings indicated the potential risks of pretransplantation blood transfusions in lung transplant recipients.

Exploring the Molecular Mechanism by which Kaempferol Attenuates Sepsis-related Acute Respiratory Distress Syndrome Based on Network Pharmacology and Experimental Verification.

Sepsis-related acute respiratory distress syndrome (ARDS) is a fatal disease without effective therapy. Kaempferol is a flavonoid compound extracted from natural plant products; it exerts numerous pharmacological effects. Kaempferol attenuates sepsis-related ARDS; however, the underlying protective mechanism has not been elucidated completely. This study aimed to use network pharmacology and experimental verification to investigate the mechanisms by which kaempferol attenuates sepsis-related ARDS. We screened the targets of kaempferol by PharMapper, Swiss Target Prediction, and CTD database. We identified the targets of sepsis-related ARDS by GeneCards, DisGeNet, OMIM, and TTD. The Weishengxin platform was used to map the targets of both kaempferol and sepsis-related ARDS. We created a Venn diagram to identify the intersection targets. We constructed the "component-intersection targets-disease" network diagram using Cytoscape 3.9.1 software. The intersection targets were imported into the STRING database for developing the protein-protein interaction network. Metascape was used for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We selected the leading 20 KEGG pathways to establish the KEGG relationship network. Finally, we performed experimental verification to confirm our prediction results. Through database screening, we obtained 502, 360, and 78 kaempferol targets, disease targets of sepsis-related ARDS, and intersection targets, respectively. The core targets consisted of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, albumin (ALB), IL-1β, and AKT serine/ threonine kinase (AKT)1. GO enrichment analysis identified 426 items, which were principally involved in response to lipopolysaccharide, regulation of inflammatory response, inflammatory response, positive regulation of cell migration, positive regulation of cell adhesion, positive regulation of protein phosphorylation, response to hormone, regulation of reactive oxygen species (ROS) metabolic process, negative regulation of apoptotic signaling pathway, and response to decreased oxygen levels. KEGG enrichment analysis identified 151 pathways. After eliminating the disease and generalized pathways, we obtained the hypoxia-inducible factor 1 (HIF-1), nuclear factor κB (NF-κB), and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways. Our experimental verification confirmed that kaempferol blocked the HIF-1, NF-κB, and PI3K-Akt signaling pathways, diminished TNF-α, IL-1β, and IL-6 expressions, suppressed ROS production, and inhibited apoptosis in lipopolysaccharide (LPS)-induced murine alveolar macrophage (MH-S) cells. Kaempferol can reduce inflammatory response, ROS production, and cell apoptosis by acting on the HIF-1, NF-κB, and PI3K-Akt signaling pathways, thereby alleviating sepsis- related ARDS.

Impact of prone position on dead-space fraction in COVID-19 related acute respiratory distress syndrome

IntroductionCOVID-19 Related Acute Respiratory Syndrome (C-ARDS) is characterized by a mismatch between respiratory mechanics and hypoxemia, suggesting increased dead-space fraction (DSF). Prone position is a cornerstone treatment of ARDS under invasive mechanical ventilation reducing mortality. We sought to investigate the impact of prone position on DSF in C-ARDS in a cohort of patients receiving invasive mechanical ventilation.Methodswe retrospectively analysed data from 85 invasively mechanically ventilated patients with C-ARDS in supine and in prone positions, hospitalized in Intensive Care Unit (Reims University Hospital), between November, 1st 2020 and November, 1st 2022. DSF was estimated via 3 formulas usable at patients’ bedside, based on partial pressure of carbon dioxide (PaCO2) and end-tidal carbon dioxide (EtCO2).Resultsthere was no difference of DSF between supine and prone position, using the 3 formulas. According to Enghoff, Frankenfield and Gattinoni equations, DSF in supine vs. prone position was in median respectively [IQR]: 0.29 [0.13–0.45] vs. 0.31 [0.19–0.51] (p = 0.37), 0.5 [0.48–0.52] vs. 0.51 [0.49–0.53] (p = 0.43), and 0.71 [0.55–0.87] vs. 0.69 [0.57–0.81], (p = 0.32).Conclusionprone position did not change DSF in C-ARDS.

Modifying Candidacy and Management to Improve Extracorporeal Support During Supply-Demand Mismatch

BackgroundCandidacy for venovenous extracorporeal membrane oxygenation is dictated by ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) criteria. We evaluated the effect of modifying candidacy on the basis of escalating demand and limited resources. MethodsWe retrospectively reviewed adult patients diagnosed with COVID-19–related severe acute respiratory distress syndrome who failed to respond to conventional ventilation and required extracorporeal support at our institution. Candidacy was restricted with a published probability model because of supply-demand mismatch and high mortality observed after the first surge. Age <55 years, mechanical ventilation days <3, and minimal comorbidities were prioritized. Primary outcomes included time to decannulation, extubation, tracheostomy, discharge, and death. Hospital and intensive care unit length of stay and hospitalization costs were evaluated. Predictors included cannulation strategy, before and after criteria implementation, use of cytoreductive techniques, timing of tracheostomy, and body mass index. Propensity score matching, multistate Cox proportional hazards models, and generalized linear models were used. ResultsOur sample comprised 105 patients, 26 from before criteria implementation (“before” phase) and 79 after (“after” phase). Propensity score results indicated no significant differences in death (P = .152) and costs (P = .063) between the groups. Patients who received cytoreductive therapy had lower total costs (P = .033). Those who underwent single-site cannulation had higher probability of decannulation (P = .009), discharge (P < .001), tracheostomy (P < .001), and extubation alive (P < .001) and lower risk of death (P = .017). ConclusionsModifying candidacy by objective criteria with the use of adjunctive therapies may improve outcomes and lower costs during periods of supply-demand mismatch.

Lung morphology changes in patients with COVID-induced acute respiratory distress syndrome depending on the respiratory therapy options

Background. Morphologic examination of lung tissue in COVID-related acute respiratory distress syndrome is shown in publications predominantly regarding the course of disease but not the type of respiratory support. The aim of the single center study was to determine the influence of different types of respiratory therapy on morphologic findings in lung tissue of patients, who had died from COVID-19. Material and methods. The examined patients with COVID-related related acute respiratory distress syndrome (n = 30) were divided into three groups. Group 1 included those who received non-invasive lung ventilation in continuous positive airway pressure (CPAP) mode through a face mask (n = 10), group 2 consisted of patients who received oxygen therapy with a flow of 15 l/min through a rebreather mask (n = 10), and group 3 included people who underwent invasive lung ventilation through an endotracheal tube (n = 10). Results. In lung tissue of patients of group 1, we revealed prevalence of edema and hemorrhagic changes as well as discrepancy of diffuse alveolar damage (DAD) manifestations and duration of the disease. So, morphological manifestations of exudative phase of DAD were found even after 14 days of disease, and interstitial pneumonia with fibrosing alveolitis was observed only in 12.5 % of patients. The presence of dystelectasis, compensatory emphysema and thinning of the alveolar wall were typical morphological findings in the patients of group 2. Numerous hyaline membranes covered alveolar walls and led to a decrease in gas exchange area, alveolar-capillary block and were the cause of impaired lung ventilation function. Morphological signs of proliferative phase of DAD in patients of group 3 were accompanied by the development of alveolar fibrosis and secondary bacterial bronchopneumonia, especially in prolonged invasive lung ventilation. Conclusions. Low-flow oxygen therapy may lead to the progression of respiratory failure due to self-damaging of intact lung tissue. We have also revealed negative impact of invasive pulmonary ventilation on the number of bacterial complications and fibrosis stimulation. The most favorable morphologic changes were found in patients with non-invasive CPAP ventilation.

Functional Capacity in COVID-19 related Acute Respiratory Distress Syndrome Survivors

Background/Purpose:: The aim of this retrospective study is to determine the functional capacity, global muscle weakness and quality of life in COVID-19 survivors. Acute respiratory distress syndrome survivors frequently develop impaired physical function, quality of life, and muscle weakness.&#x0D; Methods: Acute respiratory distress syndrome survivors related to COVID-19 underwent standardized physical clinical evaluation, Medical Research Council-sumscore, hand-grip strength, 6-minute walk test, 5 repetition-chair-stand test, timed up and go test and Short form-36 evaluation following 4-6 weeks after hospital discharge in Physical Medicine and Rehabilitation Outpatient Clinic.&#x0D; Results: Fifteen patients (10 men, 5 women) with median age 69 years and length of intensive care unit stay 10 days were analyzed. There were impairments in 6-minute walk test, 5 repetition-chair-stand test, hand-grip strength and, Role-physical, Role-emotional and Social functioning domains of Short form-36. 6-minute walk distance was negatively correlated with timed up and go. SF-physical functioning was positively correlated with hand-grip strength, Medical Research Council-sumscore and 5 repetition-chair-stand. SF-general health was positively correlated with hand-grip strength.&#x0D; Conclusion: There were varying degrees of functional impairment in survivors. Therefore, it could add advantage to assess these patients after nearly 4-6 weeks following discharge in order to ascertain rehabilitation needs and giving appropriate therapies.

Efficacy of Wharton Jelly Mesenchymal Stromal Cells infusions in moderate to severe SARS-Cov-2 related acute respiratory distress syndrome: a phase 2a double-blind randomized controlled trial.

The COVID-19 pandemic caused a wave of acute respiratory distress syndrome (ARDS) with a high in-hospital mortality, especially in patients requiring invasive mechanical ventilation. Wharton Jelly-derived Mesenchymal Stromal Cells (WJ-MSCs) may counteract the pulmonary damage induced by the SARS-CoV-2 infection through pro-angiogenic effects, lung epithelial cell protection, and immunomodulation. In this randomized, double-blind, placebo-controlled phase 2a trial, adult patients receiving invasive mechanical ventilation for SARS-CoV-2 induced moderate or severe ARDS were assigned to receive 1 intravenous infusion of 1 × 106 WJ-MSCs/kg or placebo within 48 h of invasive ventilation followed by 2 infusions of 0.5 × 106 WJ-MSCs/kg or placebo over 5 days. The primary endpoint was the percentage of patients with a PaO2/FiO2 > 200 on day 10. Thirty patients were included from November 2020 to May 2021, 15 in the WJ-MSC group and 15 in the placebo group. We did not find any significant difference in the PaO2/FiO2 ratio at day 10, with 18 and 15% of WJ-MSCs and placebo-treated patients reaching a ratio >200, respectively. Survival did not differ in the 2 groups with a 20% mortality rate at day 90. While we observed a higher number of ventilation-free days at 28 days in the WJ-MSC arm, this difference was not statistically significant (median of 11 (0-22) vs. 0 (0-18), p = 0.2). The infusions were well tolerated, with a low incidence of anti-HLA alloimmunization after 90 days. While treatment with WJ-MSCs appeared safe and feasible in patients with SARS-CoV2 moderate or severe ARDS in this phase 2a trial, the treatment was not associated with an increased percentage of patients with P/F > 200 at 10d, nor did 90 day mortality improve in the treated group. https://beta.clinicaltrials.gov/study/NCT04625738, identifier NCT04625738.

Establishment of risk prediction nomograph model for sepsis related acute respiratory distress syndrome

To explore the risk factors of acute respiratory distress syndrome (ARDS) in patients with sepsis and to construct a risk nomogram model. The clinical data of 234 sepsis patients admitted to the intensive care unit (ICU) of Tianjin Hospital from January 2019 to May 2022 were retrospectively analyzed. The patients were divided into non-ARDS group (156 cases) and ARDS group (78 cases) according to the presence or absence of ARDS. The gender, age, hypertension, diabetes, coronary heart disease, smoking history, history of alcoholism, temperature, respiratory rate (RR), mean arterial pressure (MAP), pulmonary infection, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer, oxygenation index (PaO2/FiO2), lactic acid (Lac), procalcitonin (PCT), brain natriuretic peptide (BNP), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (SCr), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) were compared between the two groups. Univariate and multivariate Logistic regression were used to analyze the risk factors of sepsis related ARDS. Based on the screened independent risk factors, a nomogram prediction model was constructed, and Bootstrap method was used for internal verification. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated to verify the prediction and accuracy of the model. There were no significant differences in gender, age, hypertension, diabetes, coronary heart disease, smoking history, alcoholism history, temperature, WBC, Hb, PLT, PT, APTT, FIB, PCT, BNP and SCr between the two groups. There were significant differences in RR, MAP, pulmonary infection, D-dimer, PaO2/FiO2, Lac, ALB, BUN, APACHE II score and SOFA score (all P < 0.05). Multivariate Logistic regression analysis showed that increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score were independent risk factors for sepsis related ARDS [RR: odds ratio (OR) = 1.167, 95% confidence interval (95%CI) was 1.019-1.336; MAP: OR = 0.962, 95%CI was 0.932-0.994; pulmonary infection: OR = 0.428, 95%CI was 0.189-0.966; Lac: OR = 1.684, 95%CI was 1.036-2.735; APACHE II score: OR = 1.577, 95%CI was 1.202-2.067; all P < 0.05]. Based on the above independent risk factors, a risk nomograph model was established to predict sepsis related ARDS (accuracy was 81.62%, sensitivity was 66.67%, specificity was 89.10%). The predicted values were basically consistent with the measured values, and the AUC was 0.866 (95%CI was 0.819-0.914). Increased RR, low MAP, pulmonary infection, high Lac and high APACHE II score are independent risk factors for sepsis related ARDS. Establishment of a risk nomograph model based on these factors may guide to predict the risk of ARDS in sepsis patients.

HYPERTENSION AND RISK FACTOR TO MORTALITY IN CORONAVIRUS DISEASE (COVID-19)

Objective: the aim of this study is to assess whether hypertension was considered a risk factor for mortality in in adult patients with COVID-19 hospitalized for acute respiratory distress syndrome (ARDS). Design and method: Retrospective study with analysis of electronic medical records of adult patients admitted for mild and moderate COVID-19 and related acute respiratory distress syndrome in a single quaternary private hospital in Rio de Janeiro, Brazil. Consecutive patients aged 18 years and older with COVID-19 confirmed by a positive reverse transcription polymerase chain reaction (RT-PCR) testing. ll data were collected in spreadsheets in Microsoft Excel version 365 (Microsoft Corp., Redmon – WA – USA) and the statistical analysis was performed using SAS Guide 4.3 (SAS Institute Inc., Cary – NV – USA). Results: Two hundred and two patients were were consecutively admitted for mild or moderate COVID-19 related ARDS and were included in this study. The mean age of the studied population was 69.1 ± 14.8 years. Of these, 130 patients (64.4%) were male. The mean BMI was 29.9 ± 6 kg/m2. Hypertension was present in 134 patients, corresponding to 67% of the studied population. 35.8% of patients had diabetes and 10.45% dyslipidemia. Among hypertensive patients, 58 (74%) died, with a relative risk of 1.45 (CI 0.96-2.2) Conclusions: The studies presented systemic arterial hypertension as the most common chronic disease in subjects diagnosed with covid-19. Hypertension is one of the main risk factors for adverse outcomes in subjects with covid-19. The results found in this study suggest that hypertension is associated with an increased risk of developing the severe form of covid-19, and increased mortality. Future studies should include the analysis of individual variables that may influence the outcome of systemic arterial hypertension subjects infected by SARS-CoV-2, such as genetic factors, race/ethnicity, occupation, lifestyle habits, in addition to the evaluation of educational level and diagnosis of the socioeconomic and environmental situation.

PULM14: Long-haul ECMO as Bridge to Transplant in COVID-19 ARDS

Background: Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (LT) is an established treatment modality for refractory acute respiratory distress syndrome (ARDS). Per the Scientific Registry of Transplant Recipients (SRTR) database, 215 patients supported on ECMO due to the Coronavirus disease of 2019 (COVID-19) related ARDS underwent LT between August 2020 and June 2022. The COVID-19 pandemic limited donor availability and increased duration of ECMO support in ECMO-dependent patients listed for LT. Outcomes of long-term ECMO as bridge to transplant (BTT) in this population remain unclear, and no cases of VV ECMO greater than 200 days has been documented in the literature. Methods: A single-center review was conducted to identify patients cannulated for VV-ECMO to treat COVID-19 associated ARDS between January 1, 2021 and January 1, 2022. Patients were selected who were supported by VV-ECMO for ARDS secondary to COVID-19 for greater than 200 days before receiving a lung transplant. Detailed analysis was performed for the outcomes and characteristics of all patients who received a lung transplant for post-COVID-19 ARDS after >200 days of VV-ECMO support. Results: Three patients were identified as long-term ECMO as BTT recipients (>200 days) for COVID-19-associated ARDS. Average age was 38 years (22,52), BMI 32.9 (31.6,34) and no patients had any known relevant respiratory medical history. One patient had a history of daily e-cigarette use. All patients were unvaccinated at the time of first positive COVID-19 test. All were successfully bridged to bilateral lung transplant (BLT) off of VV-ECMO. None required VV-ECMO post-operatively. One patient required VA-ECMO post-operatively for elevated pulmonary arterial pressures related to incidentally discovered septal defects. Average ECMO duration was 278 days (250, 324). Two patients were cannulated as bridge to recovery, and one as bridge to decision. Patients remained ambulant on ECMO support until they were able to undergo the transplant procedure. Cannulation strategies included double lumen right internal jugular (RIJ), RIJ to right femoral vein, and bifemoral venous cannulation. Complications on ECMO included sepsis, hemorrhage, stroke, reconfiguration, and atrial fibrillation. Two were discharged to home and one to inpatient rehabilitation. Average length of stay after transplant was 27 days (16,37). All 3 patients have continued to do well. Conclusion: We present three patients with the longest documented VV-ECMO support for COVID-19 ARDS a bridge to lung transplant. Our findings suggest long-term VV-ECMO support is a feasible bridge to LT for patients with COVID-19-related ARDS when used in the long-term (>200 days). The duration of ECMO support remains associated with known ECMO-related complications. Post-transplant survival to-date suggests that survival in long-term ECMO support as a BTT may be comparable to short-term ECMO in patients with COVID-19-related ARDS.

Failing categorization of severe COVID-19 ARDS into ventilatory subphenotypes studied via the clinical-histopathologic relationship

BackgroundCategorization of severe COVID-19 related acute respiratory distress syndrome (CARDS) into subphenotypes does not consider the trajectories of respiratory mechanoelastic features and histopathologic patterns. This study aimed to assess the correlation between mechanoelastic ventilatory features and lung histopathologic findings in critically ill patients who died because of CARDS. MethodsMechanically ventilated patients with severe CARDS who had daily ventilatory data were considered. The histopathologic assessment was performed through full autopsy of deceased patients. Patients were categorized into two groups according to the median worst respiratory system compliance during ICU stay (CrsICU). ResultsEighty-seven patients admitted to ICU had daily ventilatory data. Fifty-one (58.6%) died in ICU, 41 (80.4%) underwent full autopsy and were considered for the clinical-histopathological correlation analysis. Respiratory system compliance at ICU admission and its trajectory were not different in survivors and non-survivors. Median CrsICU in the deceased patients was 22.9 ml/cmH2O. An inverse correlation was found between the CrsICU and late-proliferative diffuse alveolar damage (DAD) (r = −0.381, p = 0.026). Late proliferative DAD was more extensive (p = 0.042), and the probability of stay in ICU was higher (p = 0.004) in the “low” compared to the “high” CrsICU group. Cluster analysis further endorsed these findings. ConclusionsIn critically ill mechanically ventilated patients, worsening of the respiratory system compliance correlated pathologically with the transition from early damage to late fibroproliferative patterns in non-survivors of CARDS. Categorization of CARDS into ventilatory subphenotypes by mechanoelastic properties at ICU admission does not account for the complexity of the histopathologic features.

Infiltrative monocyte derived adenosine deaminase 2 is associated with COVID-19 related acute respiratory distress syndrome

Abstract Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 characterized by immune dysregulation. The pathogenesis for this, particularly the involvement of infiltrative monocytes, is poorly understood. Extracellular ATP released during inflammation and hypoxia is rapidly scavenged into adenosine, which is further converted into inosine by adenosine deaminase (ADA). ADA2 is an extracellular isoform of ADA secreted by activated monocytes and expressed by infiltrated CD16 +CXCR3 +monocytes. Herein, we aim to study the impact of monocyte-derived ADA2 in the pathogenesis of COVID-19 associated ARDS. Critically ill COVID-19 patients were assigned to the ARDS group based on Berlin criteria, while the non-ARDS group included COVID-19 patients without any or with low-flow oxygen therapy. We observed elevated ADA activity in the serum of ARDS patients, reflecting increased level of the secreted ADA2 protein, when compared to the non-ARDS group. ARDS patients exhibited high level of circulating IL-6, CXCL8 and CXCL10. Notably, correlation analysis revealed a significant association between circulating ADA activity and CXCL10, a chemokine for CXCR3 +monocytes. Post-mortem bulk RNAseq analysis of lung tissues showed increased expression of the ADA2 gene, CECR1, along with CXCL10 suggesting intrapulmonary accumulation of ADA2 positive macrophages. These observations were further supported by the analysis of single-nuclear and spatial transcriptomic atlas of lung tissues of severe COVID-19 patients, which demonstrated a strong expression of ADA2 in CD16 +monocytes. In summary, our data suggest a potential role of infiltrative monocyte-derived ADA2 in modulating the immune response in COVID-19 related ARDS. Supported by the German Center for Infection Research (TI 07.005 to STH)

Lung transplantation for COVID-2019 respiratory failure in the United States: Outcomes 1-year posttransplant and the impact of preoperative extracorporeal membrane oxygenation support

ObjectivePatients with end-stage respiratory failure after severe coronavirus disease 2019 (COVID-19) infection may benefit from lung transplant; however, data on transplant outcomes and the impact of prolonged circulatory support before transplant in these patients are limited. MethodsWe assessed survival, postoperative complications, and the impact of pretransplant extracorporeal membrane oxygenation (ECMO) in patients undergoing lung transplant in the United States from August 2020 through March 2022 using records validated by United Network for Organ Sharing experts and extracted from the United Network for Organ Sharing database. ResultsIn 305 patients with COVID-19–related respiratory failure and validated data, survival for up to 1-year posttransplant did not differ between 188 patients with COVID-19–related acute respiratory distress syndrome and 117 patients with post-COVID-19 pulmonary fibrosis (P = .8). Pretransplant ECMO support (median 66 days) was required in 191 patients (63%), and venovenous ECMO was used in 91.2% of patients. One-, 6-, and 12-month survival was not significantly different between patients requiring ECMO and patients without ECMO (95.8% vs 99.1%, 93.1% vs 96.4%, 84.8% vs 90.9%, P = .2) In addition, 1-year survival was similar in recipients requiring ECMO for COVID-19 lung failure and recipients requiring ECMO for non-COVID-19 restrictive lung failure (84.8% vs 78.0%, P = .1). ConclusionsThese findings suggest that lung transplant in patients with COVID-19 respiratory failure yields acceptable 1-year outcomes. Despite an often more complex postoperative course, prolonged ECMO pretransplant in well-selected patients was associated with adequate clinical and functional status.

Prevalence of pulmonary hypertension in patients with COVID‐19 related lung disease listed for lung transplantation: A UNOS registry analysis

COVID-19 related lung disease (CRLD) has emerged as an indication for lung transplantation (LT) in highly select patients. The prevalence and prognostic implication of coexisting pulmonary hypertension (PH) in patients with CRLD listed for LT is not known. Adult patients in the United Network for Organ Sharing database listed for LT for COVID-19 related acute respiratory distress syndrome or fibrosis through March 2022 were identified. The prevalence and impact of precapillary PH on pre- and posttransplantation survival was determined. Time-to-event analysis was used to compare outcomes between those with and without precapillary PH. We identified 245 patients listed for LT for CRLD who had right heart catheterization data available at the time of registry listing. Median age of the cohort was 54 years (interquartile range [IQR]: 46, 60), 56 (22.9%) were female, and the median lung allocation score was 81.3 (IQR: 53.3, 89.4). The prevalence of precapillary PH at the time of transplant listing was 27.9%. There was no significant difference in pretransplant mortality in patients with and without precapillary PH (sHR: 0.5; 95% confidence interval [CI]: 0.1-1.7, p = 0.261). A total of 187 patients ultimately underwent LT; of those, 60 (31.0%) were identified as having precapillary PH during the waitlist period. Posttransplantation survival was similar between patients with and without pretransplant precapillary PH (hazard ratio: 0.96; 95% CI: 0.2-3.7, p = 0.953). We observed a high rate of concomitant precapillary PH in patients listed for LT for CRLD. Though common, coexisting precapillary PH was not associated with a significant difference in either pre- or post-transplantation outcomes.

Are There Distinct Cardiovascular Subclasses in Acute Respiratory Distress Syndrome? Maybe.

Are There Distinct Cardiovascular Subclasses in Acute Respiratory Distress Syndrome? Maybe.