Pulmonary Acute Respiratory Distress Syndrome Research Articles

The Association Between Oxygenation Status at 24 h After Diagnosis of Pulmonary Acute Respiratory Distress Syndrome and the 30-Day Mortality among Pediatric Oncological Patients.

BackgroundPediatric oncology patients with acute respiratory distress syndrome (ARDS) secondary to pneumonia are at high risk of mortality. Our aim was to describe the epidemiology of ARDS in this clinical population and to identify the association between the oxygenation status at 24 h after diagnosis and the 30-day mortality rates, stratified by the severity of ARDS.MethodsThis was a retrospective cohort study of 82 pediatric oncology patients, with a median age of 4 years, admitted to our pediatric intensive care unit with a diagnosis of ARDS between 2013 and 2021. Demographic and clinical factors were compared between the survivor (n = 52) and non-survivor (n = 30) groups. Univariate and multivariate Cox proportional hazards regression models were used to determine the association between the oxygenation status at 24 h after diagnosis and the 30-day mortality rates.ResultsThe mean airway pressure at ARDS diagnosis, PaO2/FiO2 (P/F) ratio, oxygenation index (OI) value, peak inspiratory pressure, and lactate level at 24 h after ARDS diagnosis, as well as complications (i.e., septicemia and more than two extrapulmonary organ failures) and adjunctive continuous renal replacement therapy, were significant mortality risk factors. After adjusting for other covariates, the oxygenation status P/F ratio (Hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.96–1.00, P = 0.043) and OI value (HR = 1.12, 95% CI = 1.02–1.23, P = 0.016) at 24 h remained independent mortality risk factors. According to the Kaplan–Meier survival curve, a low P/F ratio (≤ 150) and high OI (>10) were associated with a higher risk of 30-day mortality (50.9 and 52.9%, respectively; both P < 0.05)ConclusionThe P/F ratio and OI value measured at 24 h after ARDS diagnosis can provide a better stratification of patients according to ARDS disease severity to predict the 30-day mortality risk.

Ways Forward in Preventing Severe Maternal Morbidity and Maternal Health Inequities: Conceptual Frameworks, Definitions, and Data, from a Population Health Perspective.

Ways Forward in Preventing Severe Maternal Morbidity and Maternal Health Inequities: Conceptual Frameworks, Definitions, and Data, from a Population Health Perspective.

Clinical Efficacy of Budesonide/Glycopyrronium Bromide/Formoterol in the Treatment of Patients with Acute Respiratory Distress Syndrome and Its Effect on Inflammatory Factors.

Objective To examine the clinical efficacy of budesonide/glycopyrronium bromide/formoterol (Breztri Aerosphere) as an adjunct to acute respiratory distress syndrome (ARDS). Methods A prospective study enrolled 120 patients with pulmonary endogenous ARDS admitted to the Department of Critical Care Medicine at the Fourth Hospital of Baotou from January 2017 to January 2020, and all enrollments were assigned (1 : 1) to receive conventional treatment (control group) or Breztri Aerosphere (study group). Results Breztri Aerosphere was associated with a significantly higher total efficacy versus conventional treatment. Breztri Aerosphere resulted in significantly lower acute physiology and chronic health evaluation scoring system (APACHE II) scores and Murray lung injury scores versus conventional treatment. Both groups saw an increase in the partial pressure of carbon dioxide (PCO2), partial pressure of oxygen (PO2), and oxygen saturation (SaO2) after treatment, with higher levels seen in patients given Breztri Aerosphere. After treatment, systemic vascular resistance (SVR) in both groups rose markedly, with greater elevation witnessed in the study group. The patients given Breztri Aerosphere showed significantly lower levels of pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (MAPA), pulmonary artery wedge pressure (PAWP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and procalcitonin (PCT) versus those receiving conventional treatment. The patients experienced shorter mechanical ventilation time and intensive care unit (ICU) time after treatment of Breztri Aerosphere versus conventional treatment. Conclusion Adjuvant therapy with Breztri Aerosphere in ARDS can significantly lower APACHE II scores and Murray lung injury scores, improve blood gas indexes and pulmonary circulation function indexes, and shorten mechanical ventilation time and ICU time, which may be attributed to its improvement of organism inflammation status and reduction of inflammatory factors.

A Rare Case of Pulmonary Thromboembolism and Acute Respiratory Distress Syndrome (ARDS) in Scrub Typhus

Orientia tsutsugamushi causes scrub typhus, a zoonotic illness (O tsutsugamushi). The disease is spread to humans through the biting of trombiculid mite larvae (chiggers). The case report adds light to thrombus formation in scrub typhus infection, an often-under-diagnosed entity. We report a 17-year-old female who presented with complaints of breathlessness after 11 days of symptoms of fever. The condition is widespread in India, with cases reported in a number of states. Persons are infected by the larval development (chigger) of trombiculid mites. Chiggers are spread by wild rats, and illness develops when chiggers feed on humans.Laboratory investigations revealed leukocytosis, thrombocytopenia, and radiological investigations showed ARDS and pleural effusion, and the patient was diagnosed to have scrub typhus. Treatment was given for the infection and its complications.

Pulmonary Infarction and Acute Respiratory Distress Syndrome Resulted from Small Amount of Peripheral Pulmonary Cement Embolism following Cement-Augmented Pedicle Screw Fixation: A Rare Case and Literature Review

The information about symptomatic pulmonary cement embolism (PCE) following vertebroplasty and cement-augmented pedicle screw fixation is limited. To our knowledge, this is the first reported case of severe acute respiratory distress syndrome (ARDS) caused by a relatively small amount of peripheral PCE, which resulted in mortality.

L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis.

SUMMARYMacrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome. We find that the actin-bundling protein L-plastin (LPL) significantly enhances NLRP3 assembly. Specifically, LPL enables apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) oligomerization during NLRP3 assembly by stabilizing ASC interactions with the kinase Pyk2, a component of cell-surface adhesive structures called podosomes. Upon treatment with exogenous NLRP3 activators, lung-resident alveolar macrophages (AMs) lacking LPL exhibit reduced caspase-1 activity, IL-1β cleavage, and gasdermin-D processing. LPL−/− mice display resistance to bleomycin-induced lung injury and fibrosis. These findings identify the LPL-Pyk2-ASC pathway as a target for modulation in NLRP3-mediated inflammatory conditions.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Serum Surfactant Protein-D (SP-D) Level: Does it Correlates with Pulmonary Compliance and ARDS in Severe Cases of COVID-19?

Acute Respiratory Distress Syndrome (ARDS) happens to 67% of all severe COVID-19 cases with mortality rate of 50-94%. Main characteristics of ARDS are poor oxygenation and non-compliant lungs. The lungs are like inflatable balloons that are actively inflated by the positive pressure within and/or the negative pressure created in the pleural cavity. Compliance is the ability of the lungs to distend at a certain level of transpulmonary pressure. Surfactant lowers the surface tension of the alveoli so that end-expiratory pulmonary collapse could be prevented and pulmonary compliance could be maintained. Surfactants also play an important role in the host's defense against infection. Surfactants comprise of phospholipids, cholesterol and surfactant proteins (SP) SP-A, -B, -C and –D. Previous study showed that concentration of SP-D was significantly higher in ARDS patients. Higher serum SP-D concentrations were associated with a greater risk of death, fewer ventilator-free days, and fewer organ failure-free days. This review highlights the role of surfactant especially SP-D in pulmonary compliance and ARDS in COVID-19.

Additional effect of azithromycin over \u03b2-lactam alone for severe community-acquired pneumonia-associated acute respiratory distress syndrome: a retrospective cohort study

BackgroundCommunity-acquired pneumonia (CAP) is the most common cause of acute respiratory distress syndrome (ARDS). Although previous studies have suggested that macrolide therapy is beneficial for ARDS, its benefit for severe CAP-associated ARDS remains uncertain. Previous studies were limited in that they had a small sample size and included patients with non-pulmonary ARDS and those with pulmonary ARDS. This study aimed to investigate the additional effect of azithromycin when used with β-lactam compared with the effect of β-lactam alone in mechanically ventilated patients with CAP-associated ARDS.MethodsWe identified mechanically ventilated patients with CAP-associated ARDS between July 2010 and March 2015 using data in the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database. We performed propensity score matching analysis to assess 28-day mortality and in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS who received β-lactam with and without azithromycin within hospital 2 days after admission. The inverse probability of treatment weighting analysis was also conducted.ResultsEligible patients (n = 1257) were divided into the azithromycin group (n = 226) and the control group (n = 1031). The one-to-four propensity score matching analysis included 139 azithromycin users and 556 non-users. No significant difference was observed between the groups with respect to 28-day mortality (34.5% vs. 37.6%, p = 0.556) or in-hospital mortality (46.0% vs. 49.1%, p = 0.569). The inverse probability of treatment weighting analysis showed similar results.ConclusionsCompared with treatment with β-lactam alone, treatment with azithromycin plus β-lactam had no significant additional effect on 28-day mortality or in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS. To the best of our knowledge, this study is the first to determine the effect of azithromycin in mechanically ventilated patients with CAP-associated ARDS.

An exploration of pulmonary fitness of construction workers in Delhi NCR in light of the building and other construction workers act, 1996.

Workers in the construction sector are exposed to high concentrations of particulate matter at their workplace. This increases their susceptibility to various respiratory diseases, particularly chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS). The study reports comparative pulmonary fitness and hematological parameters of the migrant workers in the construction sector versus other sectors in Delhi. Parameters such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the ratio of FEV1 to FVC, and peak expiratory flow were measured in both groups using a spirometer. We observed significant differences (P < 0.05) in FEV1 and FVC between both groups. The study thus confirms that workers exposed to poor air quality at the construction site are susceptible to respiratory diseases, particularly ARDS. All of this reflects the poor enforcement of the adequate safety measures well enlisted in social legislations such as the Building and Other Construction Workers Act.

Current Overview on Therapeutic Potential of Vitamin D in Inflammatory Lung Diseases.

Inflammatory lung disorders (ILDs) are one of the world’s major reasons for fatalities and sickness, impacting millions of individuals of all ages and constituting a severe and pervasive health hazard. Asthma, lung cancer, bronchiectasis, pulmonary fibrosis acute respiratory distress syndrome, and COPD all include inflammation as a significant component. Microbe invasions, as well as the damage and even death of host cells, can cause and sustain inflammation. To counteract the negative consequences of irritants, the airways are equipped with cellular and host defense immunological systems that block the cellular entrance of these irritants or eliminate them from airway regions by triggering the immune system. Failure to activate the host defense system will trigger chronic inflammatory cataracts, leading to permanent lung damage. This damage makes the lungs more susceptible to various respiratory diseases. There are certain restrictions of the available therapy for lung illnesses. Vitamins are nutritional molecules that are required for optimal health but are not produced by the human body. Cholecalciferol (Vitamin D) is classified as a vitamin, although it is a hormone. Vitamin D is thought to perform a function in bone and calcium homeostasis. Recent research has found that vitamin D can perform a variety of cellular processes, including cellular proliferation; differentiation; wound repair; healing; and regulatory systems, such as the immune response, immunological, and inflammation. The actions of vitamin D on inflammatory cells are dissected in this review, as well as their clinical significance in respiratory illnesses.

Hantavirus.

Hantaviruses are tri-segmented lipid-enveloped RNA viruses belonging to the Bunyaviridae family. Human infection corresponds to a zoonosis associated with two different clinical syndromes: hemorrhagic fever with renal syndrome that occurs in Asia and Europe and hantavirus cardiopulmonary syndrome (HCPS) that occurs in the North America, Central America and South America. The major pathogenic mechanisms in HCPS include (1) direct microvascular endothelial injury leading to increased capillary permeability and the development of noncardiogenic pulmonary edema and acute respiratory distress syndrome, and (2) exaggerated host immune response leading to secondary organ damage. The incubation period for this disease is quite long (6-39 days, median: 18 days); however, rapid progression to respiratory failure and shock can occur highlighting the importance of high index of clinical suspicion. Management revolves around high-quality supportive care. Various management and preventative strategies are currently being explored and warrant further examination to improve the overall outlook following infection with hantavirus.

The Association Between Etiologies and Mortality in Acute Respiratory Distress Syndrome: A Multicenter Observational Cohort Study.

Background: Lung-protective ventilation (LPV) strategies have been beneficial in patients with acute respiratory distress syndrome (ARDS). As a vital part of LPV, positive end-expiratory pressure (PEEP) can enhance oxygenation. However, randomized clinical trials of different PEEP strategies seem to show no advantages in clinical outcomes in patients with ARDS. A potential reason is that diverse etiologies and phenotypes in patients with ARDS may account for different PEEP responses, resulting in variations in mortality. We consider hospital mortality to be associated with a more specific classification of ARDS, such as sepsis induced or not, and pulmonary or extrapulmonary one. Our study aimed to compare clinical outcomes in various patients with ARDS by etiologies using the China Critical Care Sepsis Trial (CCCST) database. This was a retrospective analysis of a prospective cohort of 2,138 patients with ARDS in the CCCST database. According to ARDS induced by sepsis or not and medical history, patients were stratified into different four groups. Differences among groups were assessed in hospital mortality, ventilation-free days, and other clinical features.Results: A total of 2,138 patients with ARDS were identified in the database, including 647 patients with sepsis-induced pulmonary ARDS (30.3%), 396 patients with sepsis-induced extrapulmonary ARDS (18.5%), 536 patients with non-sepsis pulmonary ARDS (25.1%), and 559 patients with non-sepsis extrapulmonary ARDS (26.1%). The pulmonary ARDS group had higher mortality compared with the extrapulmonary group (45.9 vs. 23.0%, p < 0.01), longer intensive care unit (ICU) and hospital stays (9 vs. 6 days, p < 0.01, 20 vs. 18 days, p = 0.01, respectively), and fewer ventilation-free days (5 vs. 9 days) in the presence of sepsis. However, the mortality in ARDS without sepsis was inverted compared with extrapulmonary ARDS (pulmonary 23.5% vs. extrapulmonary 29.2%, p = 0.04). After adjusting for the Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores and other clinical features, the sepsis-induced pulmonary condition was still a risk factor for death in patients with ARDS (hazard ratio 0.66, 95% CI, 0.54–0.82, p < 0.01) compared with sepsis-induced extrapulmonary ARDS and other subphenotypes.Conclusions: In the presence of sepsis, hospital mortality in pulmonary ARDS is higher compared with extrapulmonary ARDS; however, mortality is inverted in ARDS without sepsis. Sepsis-induced pulmonary ARDS should attract more attention from ICU physicians and be cautiously treated.Trial registration: ChiCTR-ECH-13003934. Registered August 3, 2013, http://www.chictr.org.cn.

Factors Associated with Prolonged Hospital Length of Stay in Adults with Imported Falciparum Malaria-An Observational Study from a Tertiary Care University Hospital in Berlin, Germany.

Outcome of falciparum malaria is largely influenced by the standard of care provided, which in turn depends on the available medical resources. Worldwide, the COVID-19 pandemic has had a major impact on the availability of these resources, even in resource-rich healthcare systems such as Germany’s. The present study aimed to determine the under-explored factors associated with hospital length of stay (LOS) in imported falciparum malaria to identify potential targets for improving management. This retrospective observational study used multivariate Cox proportional hazard regression with time to discharge as an endpoint for adults hospitalized between 2001 and 2015 with imported falciparum malaria in the Charité University Hospital, Berlin. The median LOS of the 535 cases enrolled was 3 days (inter-quartile range, IQR, 3–4 days). The likelihood of being discharged by day 3 strongly decreased with severe malaria (hazard ratio, HR, 0.274; 95% Confidence interval, 95%CI: 0.190–0.396) and by 40% with each additional presenting complication (HR, 0.595; 95%CI: 0.510–0.694). The 55 (10.3%) severe cases required a median LOS of 7 days (IQR, 5–12 days). In multivariate analysis, occurrence of shock (adjusted HR, aHR, 0.438; 95%CI 0.220–0.873), acute pulmonary oedema or acute respiratory distress syndrome (aHR, 0.450; 95%CI: 0.223–0.874), and the need for renal replacement therapy (aHR, 0.170; 95%CI: 0.063–0.461) were independently associated with LOS. All patients survived to discharge. This study illustrates that favourable outcomes can be achieved with high-standard care in imported falciparum malaria. Early recognition of disease severity together with targeted supportive care can lead to avoidance of manifest organ failure, thereby potentially decreasing LOS and alleviating pressure on bed capacities.

Effect of Dihydropyridine Calcium Channel Blocker on Mortality of Hypertension Patients With Moderate-Severe Pulmonary Acute Respiratory Distress Syndrome: A Multicenter Retrospective Observational Cohort Study.

A retrospective, observational, multicenter cohort study. A total of 307 patients without propensity score matching and 186 adult inpatients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome in five teaching hospitals in Jiangsu province, China, from December 2015 to December 2020 were enrolled. A total of 307 patients without propensity score matching and 186 patients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome were included in the final analysis. None. Demographic characteristics and clinical characteristics were recorded. The propensity score matching method was used to eliminate the difference between group with dihydropyridine calcium channel blocker and group without dihydropyridine calcium channel blocker. The primary outcome was in-hospital mortality. We used univariate and multivariate regression analyses for both patients with or without propensity score matching to assess the effect of these variables on mortality. In the subset of 186 patients with propensity score matching, in-hospital mortality was 53.2%. Inpatient mortality was significantly higher in patients treated with dihydropyridine calcium channel blocker than in those not treated with dihydropyridine calcium channel blocker of patients without propensity score matching (65.4% vs 40.4%; p < 0.01). Multivariate analysis for patients without propensity score matching showed that dihydropyridine calcium channel blocker (hazard ratio, 1.954; 95% CI, 1.415-2.699), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 3.809; 95% CI, 2.106-4.531), and lactate greater than or equal to 2 mmol/L (hazard ratio, 1.454; 95% CI, 1.041-2.029) were independently associated with in-hospital mortality. Based on univariate analysis for patients with propensity score matching, dihydropyridine calcium channel blocker (hazard ratio, 2.021; 95% CI, 1.333-3.064), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 4.379; 95% CI, 2.642-7.257), and lactate greater than or equal to 2 mmol/L (hazard ratio, 2.461; 95% CI, 1.534-3.951) were independently associated with in-hospital mortality. In contrast, patients not treated with dihydropyridine calcium channel blocker had a significant survival advantage over those treated with dihydropyridine calcium channel blocker in both patients without or with propensity score matching (p < 0.001; p = 0.001 by Kaplan-Meier analysis). Dihydropyridine calcium channel blocker, lactate dehydrogenase greater than or equal to 600 U/L, and lactate greater than or equal to 2 mmol/L at admission were independent risk factors for patients with hypertension and moderate-severe pulmonary acute respiratory distress syndrome.

Extracorporeal carbon dioxide removal (ECCO2R) in COPD and ARDS patients with severe hypercapnic respiratory failure. A retrospective case-control study

Background/aim Treatment of severe hypercapnic respiratory failure (HRF) has some challenges in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS), especially when lung protective ventilation (LPV) strategies are required. Extracorporeal CO2 removal (ECCO2R) therapy is an emerging option to manage hypercapnia while allowing LPV in these cases. However, further data on ECCO2R use is still needed to make clear recommendations.Materials and methods This study was conducted on patients admitted to intensive care unit (ICU) between January 1st, 2016 to December 31st, 2019. The medical records were retrospectively scanned in institutional software database. Patients who received invasive mechanic ventilation (iMV) support due to severe HRF related to COPD or ARDS were included in the analyses. Patients were grouped according to treatment approaches as that ECCO2R therapy in addition to conventional treatments and conventional treatments alone (controls). Groups were compared for 28-day survival, iMV duration, and length of stay (LOS).Results ECCO2R therapy was noted in 75 of the cases among included 395 patients (COPD n = 256, ARDS n = 139) out of scanned 1715 medical records. The survival rate of ECCO2R patients was 68% and significantly higher than 58% survival rate of controls (p = 0.025), with relative risk reduction (RRR) = 0.16, absolute risk reduction (ARR)= 0.10, number need to treat (NNT) = 10, and odds ratio (OR) = 1.5. In addition, iMV duration (12.8 ± 2.6 vs. 17.1 ± 4.9 days, p = 0.007) and LOS (16.9 ± 4.1 vs. 18.9 ± 5.5 days, p = 0.032) were significantly shorter than controls. Repeated measure analyses showed that LPV settings were successfully provided by 72 h of ECCO2R therapy. Subgroup analyses according to diagnoses of COPD and ARDS also favored ECCO2R.Conclusion ECCO2R therapy significantly improved survival, iMV duration and LOS in patients with severe HRF due to COPD or ARDS, and successfully provided LPV approaches. Further studies are needed to assess promising benefits of ECCO2R therapy.

Association between ARDS Etiology and Risk of Noninvasive Ventilation Failure.

Rationale: The etiology of acute respiratory distress syndrome (ARDS) may play an important role in the failure of noninvasive ventilation (NIV). Objectives: To explore the association between ARDS etiology and risk of NIV failure. Methods: A multicenter prospective observational study was performed in 17 intensive care units in China from September 2017 to December 2019. Patients with ARDS who used NIV as a first-line therapy were enrolled. The etiology of ARDS was recorded at study entry. Results: A total of 306 patients were enrolled. Of the patients, 146 were classified as having pulmonary ARDS (ARDSp) and 160 were classified as having extrapulmonary ARDS (ARDSexp). From initiation to 24 hours of NIV, the respiratory rate, heart rate, arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2), and arterial carbon dioxide pressure improved slower in patients with ARDSp than those with ARDSexp. Patients with ARDSp experienced more NIV failure (55% vs. 28%; P < 0.01) and higher 28-day mortality (47% vs. 14%; P < 0.01). The adjusted odds ratios of NIV failure and 28-day mortality were 5.47 (95% confidence interval [CI], 3.04-9.86) and 10.13 (95% CI, 5.01-20.46), respectively. In addition, we combined the presence of ARDSp, presence of septic shock, age, nonpulmonary sequential organ failure assessment score, respiratory rate at 1-2 hours of NIV, and PaO2/FiO2 at 1-2 h of NIV to develop a risk score of NIV failure. With the increase of the risk score, the rate of NIV failure increased. The area under the curve of the receiver operating characteristic was 0.84 (95% CI, 0.79-0.89) and 0.81 (0.69-0.92) in the training and validation cohorts, respectively. Using 5.5 as cutoff value to predict NIV failure, the sensitivity and specificity was good. Conclusions: Among patients with ARDS who used NIV as a first-line therapy, ARDSp was associated with slower improvement, more NIV failure, and higher 28-day mortality than ARDSexp. The risk score combined presence of ARDSp, presence of septic shock, age, nonpulmonary sequential organ failure assessment score, respiratory rate at 1-2 hours of NIV, and PaO2/FiO2 at 1-2 hours of NIV has high accuracy to predict NIV failure among ARDS population.

Longitudinal changes in compliance, oxygenation and ventilatory ratio in COVID-19\xa0versus\xa0non-COVID-19 pulmonary acute respiratory distress syndrome

BackgroundDifferences in physiology of ARDS have been described between COVID-19 and non-COVID-19 patients. This study aimed to compare initial values and longitudinal changes in respiratory system compliance (CRS), oxygenation parameters and ventilatory ratio (VR) in patients with COVID-19 and non-COVID-19 pulmonary ARDS matched on oxygenation.Methods135 patients with COVID-19 ARDS from two centers were included in a physiological study; 767 non-COVID-19 ARDS from a clinical trial were used for the purpose of at least 1:2 matching. A propensity-matching was based on age, severity score, oxygenation, positive end-expiratory pressure (PEEP) and pulmonary cause of ARDS and allowed to include 112 COVID-19 and 198 non-COVID pulmonary ARDS.ResultsThe two groups were similar on initial oxygenation. COVID-19 patients had a higher body mass index, higher CRS at day 1 (median [IQR], 35 [28–44] vs 32 [26–38] ml cmH2O−1, p = 0.037). At day 1, CRS was correlated with oxygenation only in non-COVID-19 patients; 61.6% and 68.2% of COVID-19 and non-COVID-19 pulmonary ARDS were still ventilated at day 7 (p = 0.241). Oxygenation became lower in COVID-19 than in non-COVID-19 patients at days 3 and 7, while CRS became similar. VR was lower at day 1 in COVID-19 than in non-COVID-19 patients but increased from day 1 to 7 only in COVID-19 patients. VR was higher at days 1, 3 and 7 in the COVID-19 patients ventilated using heat and moisture exchangers compared to heated humidifiers. After adjustment on PaO2/FiO2, PEEP and humidification device, CRS and VR were found not different between COVID-19 and non-COVID-19 patients at day 7. Day-28 mortality did not differ between COVID-19 and non-COVID-19 patients (25.9% and 23.7%, respectively, p = 0.666).ConclusionsFor a similar initial oxygenation, COVID-19 ARDS initially differs from classical ARDS by a higher CRS, dissociated from oxygenation. CRS become similar for patients remaining on mechanical ventilation during the first week of evolution, but oxygenation becomes lower in COVID-19 patients.Trial registration: clinicaltrials.gov NCT04385004

The Clinical Characteristics of ARDS in Children With Hematological Neoplasms.

In order to explore the clinical characteristics of pediatric patients admitted to the pediatric intensive care unit (PICU) who suffered from hematological neoplasms complicated with acute respiratory distress syndrome (ARDS), we retrospectively analyzed 45 ARDS children with hematological neoplasms who were admitted to the PICU of Shanghai Children's Medical Center from January 1, 2014, to December 31, 2020. The 45 children were divided into a survival group and a non-survival group, a pulmonary ARDS group and an exogenous pulmonary ARDS group, and an agranulocytosis group and a non-agranulocytosis group, for statistical analysis. The main clinical manifestations were fever, cough, progressive dyspnea, and hypoxemia; 55.6% (25/45) of the children had multiple organ dysfunction syndrome (MODS). The overall mortality rate was 55.6% (25/45). The vasoactive inotropic score (VIS), pediatric critical illness scoring (PCIS), average fluid volume in the first 3 days and the first 7 days, and the incidence of MODS in the non-survival group were all significantly higher than those in the survival group (P < 0.05). However, total length of mechanical ventilation and length of hospital stay and PICU days in the non-survival group were significantly lower than those in the survival group (P < 0.05). The PCIS (OR = 0.832, P = 0.004) and the average fluid volume in the first 3 days (OR = 1.092, P = 0.025) were independent risk factors for predicting death. Children with exogenous pulmonary ARDS were more likely to have MODS than pulmonary ARDS (P < 0.05). The mean values of VIS, C-reactive protein (CRP), and procalcitonin (PCT) in children with exogenous pulmonary ARDS were also higher (P < 0.05). After multivariate analysis, PCT was independently related to exogenous pulmonary ARDS. The total length of hospital stay, peak inspiratory pressure (PIP), VIS, CRP, and PCT in the agranulocytosis group were significantly higher than those in the non-agranulocytosis group (P < 0.05). Last, CRP and PIP were independently related to agranulocytosis. In conclusion, children with hematological neoplasms complicated with ARDS had a high overall mortality and poor prognosis. Children complicated with MODS, positive fluid balance, and high VIS and PCIS scores were positively correlated with mortality. In particular, PCIS score and average fluid volume in the first 3 days were independent risk factors for predicting death. Children with exogenous pulmonary ARDS and children with agranulocytosis were in a severely infected status and more critically ill.

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype

BackgroundWe recently reported histone methyltransferase enhancer of zeste homolog 2 (EZH2) as a key epigenetic regulator that contributes to the dysfunction of innate immune responses to sepsis and subsequent lung injury by mediating the imbalance of macrophage polarization. However, the role of EZH2 in acute respiratory distress syndrome (ARDS)-associated fibrosis remains poorly understood.MethodsIn this study, we investigated the role and mechanisms of EZH2 in pulmonary fibrosis in a murine model of LPS-induced ARDS and in ex-vivo cultured alveolar macrophages (MH-S) and mouse lung epithelial cell line (MLE-12) by using 3-deazaneplanocin A (3-DZNeP) and EZH2 the small interfering (si) RNA.ResultsWe found that treatment with 3-DZNeP significantly ameliorated the LPS-induced direct lung injury and fibroproliferation by blocking EMT through TGF-β1/Smad signaling pathway and regulating shift of macrophage phenotypes. In the ex-vivo polarized alveolar macrophages cells, treatment with EZH2 siRNA or 3-DZNeP suppressed the M1 while promoted the M2 macrophage differentiation through modulating the STAT/SOCS signaling pathway and activating PPAR-γ. Moreover, we identified that blockade of EZH2 with 3-DZNeP suppressed the epithelial to mesenchymal transition (EMT) in co-cultured bronchoalveolar lavage fluid (BALF) and mouse lung epithelial cell line through down-regulation of TGF-β1, TGF-βR1, Smad2 while up-regulation of Smad7 expression.ConclusionsThese results indicate that EZH2 is involved in the pathological process of ARDS-associated pulmonary fibrosis. Targeting EZH2 may be a potential therapeutic strategy to prevent and treat pulmonary fibrosis post ARDS.