Mortality In Acute Respiratory Distress Syndrome Research Articles

Mortality of Adult Respiratory Distress Syndrome in Trauma Patients: A Systematic Review over a Period of Four Decades.

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality. In addition, its aetiologies are heterogeneous, and the outcome depends on the underlying cause. In trauma care, changes in diagnostics, management and treatment may influence the outcome of posttraumatic ARDS over time, which are attributable to geographic distribution, relate to the definition used and depend on the injury severity. We selected studies by searching PubMed using the MeSH terms "acute respiratory distress syndrome", "mortality" and "trauma" and all their combinations. Studies that reported mortality rates for polytrauma patients with ARDS were included. We excluded studies with selected population collectives (e.g. burn patients, isolated thoracic trauma and paediatric trauma) and non-trauma studies. Studies were stratified according to the recruitment year of patients into Decade 1 (prior 1990), Decade 2(1990-1999), Decade 3 (2000-2009) and Decade 4 (later 2009); geographic location (North America or Europe), the definition used in the different studies (American European Consensus Conference (AECC) definition or Berlin definition) and the mean injury severity of the patient populations, respectively. Twenty-three studies between 1 January 1980 and 30 June 2018 were included in the analysis (486,861 patients, 52,561 with posttraumatic ARDS). There was a wide variation in mortality rates among the studies (4-39%). The overall pooled mean mortality rate for all studies was 21.8%, SD ± 8.3%. The mean mortality over the last four decades was similar between decade 1 (25.8%), decade 2 (20.6%), decade 3 (20.7%) and decade 4 (22.5%). Geographical observations comparing Europe and North America revealed no difference [Europe (22.1%) and North America (21.7%)]. The ARDS mortality in publications using the Berlin definition (23%) was comparable to the mortality rate in publications using the AECC definition (22.9%). The mortality rate based on the injury severity showed no alteration (ISS ≤ 25 points, 22.6%, ISS > 25 points, 22.6%). In this systematic review, there was no change in the mortality rate over the last four decades, no geographical difference within Western societies, no dependence on the ARDS definition used and no association with injury severity, respectively.

Insight into ECMO, Mortality and ARDS: A Nationwide Analysis of 45,647 ECMO Runs

Background: Extracorporeal life support (ECLS) has become an integral part of modern intensive therapy. The choice of support mode depends largely on the indication. Patients with respiratory failure are predominantly treated with a venovenous (VV) approach. Methods: Inpatient data from Germany from 2007 to 2018 provided by the Federal Statistical Office of Germany were analysed. The ICD and OPS codes for extracorporeal membrane oxygenation (ECMO) types, acute respiratory distress syndrome (ARDS) and hospital mortality were used. Findings: A total of 45,647 hospitalized patients treated with ECLS were analysed. Overall hospital mortality remains higher than predicted in comparison to the values reported in the literature. The number of VV-ECMO cases increased by 236% percent from 825 in 2005 to 2,768 in 2018. ARDS was the main indication for VV-ECMO in only 33% of the patients in the past, but that proportion increased to 60% in 2018. VA-ECMO support is of minor importance in the treatment of ARDS in Germany. The age distribution of patients undergoing ECLS has shifted towards an older population. Interpretation: ARDS is a severe disease with a high mortality rate despite ECLS therapy. The mortality rate differs widely in studies such as the CESAR trial and the EOLIA trial and the ELSO Registry in Germany. Funding Statement: This study was supported by internal institutional research funds from the Department of Anaesthesiology, Intensive Care and Pain Therapy, University Hospital Frankfurt, Goethe University, Frankfurt Germany. Declaration of Interests: Dr. Mutlak received lecture fees from GETINGE and conducted workshops for GETINGE. Dr. Friedrichson, Dr. Piekarski and Prof. Zacharowski have no conflicts of interest regarding the article.

Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies.

Background:Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous studies showed the relationship between Ang-2 level and the risk of mortality in patients with acute respiratory distress syndrome (ARDS). However, the link between circulating Ang-2 and the risk of mortality in patients with ARDS varied in different investigations.Results:We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating Ang-2 and mortality in patients with ARDS. Among the 10 eligible studies, pooled odds ratio (OR) showed that high Ang-2 level contributed to ARDS mortality [OR = 1.56, 95% confidence interval (CI): 1.30–1.89, I2 = 76.2%]. Stratified analysis revealed that higher circulating Ang-2 was related to a 30% higher risk in the high-quality scores group (OR = 1.68, 95% CI: 1.33–2.68, I2 = 62.4%). The I2 of the bad compliance group decreased from 76.2% to 8.5%, which suggested that compliance is a significant source of heterogeneity. This association may be blunted by potential bias, although the results was not meaningfully changed by omitting only one study at a time. Further subgroup analysis and meta-regression support that compliance of patients also affects the results significantly, compared with the publication year, follow-up duration, the samples, or population characteristics.Conclusion:Participants with higher baseline Ang-2 were at a higher risk for future risk of mortality in patients with ARDS. Higher circulating Ang-2 levels could independently predict the risk of mortality in patients with ARDS. However, further large scale prospective cohorts or even interventional studies are warranted to evaluate the diagnostic power of Ang-2 and its causative role on ARDS outcome. The reviews of this paper are available via the supplemental material section.

Injury Characteristics and von Willebrand Factor for the Prediction of Acute Respiratory Distress Syndrome in Patients With Burn Injury: Development and Internal Validation.

To derive and validate a prediction model for the development of ARDS in burn-injured patients. Burn injury carries the highest incidence of acute respiratory distress syndrome (ARDS) among all predisposing conditions, but few studies exist on risk factors in these patients. Studies employing biomarkers and clinical risk factors for predicting ARDS mortality have recently been examined but none exist for onset of ARDS nor in patients with burn injury. This was a prospective multicenter study of 113 patients with isolated burn injury or inhalation injury. Clinical variables and plasma biomarkers representative of endothelial injury, epithelial injury, or inflammation were collected within 24 hours of admission. The most parsimonious model was chosen by considering discrimination, calibration, and model fit. Among the biomarkers measured in patients with burn injuries, a one-standard deviation increase in log-transformed levels of the A2 domain of von Willebrand factor in the first 24 hours was most strongly associated with the development of ARDS (OR 7.72; 95% CI: 1.64-36.28, P = 0.03). Of candidate models, a 3-variable model with %TBSA, inhalation injury, and von Willebrand factor-A2 had comparable discrimination to more complex models (area under the curve: 0.90; 95% CI 0.85-0.96). The 3-variable model had good model fit by Hosmer-Lemeshow test (P = 0.74) and maintained similar discrimination after accounting for performance optimism (Bootstrapped area under the curve: 0.90; 95% CI: 0.84-0.95). The 3-variable model with %TBSA, inhalation injury, and von Willebrand factor could be used to better identify at-risk patients for both the study and prevention of ARDS in patients with burn injury.

Estimated dead space fraction and the ventilatory ratio are associated with mortality in early ARDS

BackgroundIndirect indices for measuring impaired ventilation, such as the estimated dead space fraction and the ventilatory ratio, have been shown to be independently associated with an increased risk of mortality. This study aimed to compare various methods for dead space estimation and the ventilatory ratio in patients with acute respiratory distress syndrome (ARDS) and to determine their independent values for predicting death at day 30. The present study is a post hoc analysis of a prospective observational cohort study of ICUs of two tertiary care hospitals in the Netherlands.ResultsIndividual patient data from 940 ARDS patients were analyzed. Estimated dead space fraction and the ventilatory ratio at days 1 and 2 were significantly higher among non-survivors (p < 0.01). Dead space fraction calculation using the estimate from physiological variables [VD/VT phys] and the ventilatory ratio at day 2 showed independent association with mortality at 30 days (odds ratio 1.28 [95% CI 1.02–1.61], p < 0.03 and 1.20 [95% CI, 1.01–1.40], p < 0.03, respectively); whereas, the Harris–Benedict [VD/VT HB] and Penn State [VD/VT PS] estimations were not associated with mortality. The predicted validity of the estimated dead space fraction and the ventilatory ratio improved the baseline model based on PEEP, PaO2/FiO2, driving pressure and compliance of the respiratory system at day 2 (AUROCC 0.72 vs. 0.69, p < 0.05).ConclusionsEstimated methods for dead space calculation and the ventilatory ratio during the early course of ARDS are associated with mortality at day 30 and add statistically significant but limited improvement in the predictive accuracy to indices of oxygenation and respiratory system mechanics at the second day of mechanical ventilation.

Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome

BackgroundThe lung microbiome maintains the homeostasis of the immune system within the lungs. In acute respiratory distress syndrome (ARDS), the lung microbiome is enriched with gut-derived bacteria; however, the specific microbiome associated with morbidity and mortality in patients with ARDS remains unclear. This study investigated the specific patterns of the lung microbiome that are correlated with mortality in ARDS patients.MethodsWe analyzed the lung microbiome from the bronchoalveolar lavage fluid (BALF) of patients with ARDS and control subjects. We measured the copy numbers of 16S rRNA and the serum and BALF cytokines (interleukin [IL]-6, IL-8, receptor for advanced glycation end products, and angiopoietin-2).ResultsWe analyzed 47 mechanically ventilated patients diagnosed with (n = 40) or without (n = 7; control) ARDS. The alpha diversity was significantly decreased in ARDS patients compared with that of the controls (6.24 vs. 8.07, P = 0.03). The 16S rRNA gene copy numbers tended to be increased in the ARDS group compared with the controls (3.83 × 106 vs. 1.01 × 105 copies/mL, P = 0.06). ARDS patients were subdivided into the hospital survivor (n = 24) and non-survivor groups (n = 16). Serum IL-6 levels were significantly higher in the non-survivors than in the survivors (567 vs. 214 pg/mL, P = 0.027). The 16S rRNA copy number was significantly correlated with serum IL-6 levels in non-survivors (r = 0.615, P < 0.05). The copy numbers and relative abundance of betaproteobacteria were significantly lower in the non-survivors than in the survivors (713 vs. 7812, P = 0.012; 1.22% vs. 0.08%, P = 0.02, respectively). Conversely, the copy numbers of Staphylococcus, Streptococcus and Enterobacteriaceae were significantly correlated with serum IL-6 levels in the non-survivors (r = 0.579, P < 0.05; r = 0.604, P < 0.05; r = 0.588, P < 0.05, respectively).ConclusionsThe lung bacterial burden tended to be increased, and the alpha diversity was significantly decreased in ARDS patients. The decreased Betaproteobacteria and increased Staphylococcus, Streptococcus and Enterobacteriaceae might represent a unique microbial community structure correlated with increased serum IL-6 and hospital mortality.Trial registrationThe institutional review boards of Hiroshima University (Trial registration: E-447-4, registered 16 October 2019) and Kyoto Prefectural University of Medicine (Trial registration: ERB-C-973, registered 19 October 2017) approved an opt-out method of informed consent.

Cumulative fluid balance predicts mortality and increases time on mechanical ventilation in ARDS patients: An observational cohort study.

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

Clinical outcomes of acute respiratory distress syndrome in a university hospital

Abstract Background Mortality rates of acute respiratory distress syndrome (ARDS) are different, depending on severity, etiology, and management. Objective To determine 7-day and 28-day mortalities, hospital length of stay (LOS), duration of mechanical ventilation (MV) of ARDS patients, and factors associated with poor outcomes. Methods A retrospective study was conducted to review the database of ARDS patients admitted in medical intensive care units (ICUs) at a university hospital between 2010 and 2014. The cases were identified by using International Classification of Diseases, 10th Revision (ICD-10) code-J80 ARDS. Results Of 266 patients, 11.7%, 44.4%, and 44% fulfilled mild, moderate, and severe ARDS criteria, respectively. The main cause of ARDS was pneumonia. The 7-day and 28-day mortalities, median LOS, and median MV duration were 31.1%, 69.3%, 18, and 11 days, respectively. Pressure control was the most favorite mode, used with average tidal volume (TV) of 8.63 (2.16) mL/kg ideal body weight (IBW). Recruitment maneuver was most frequently used as adjunctive intervention, whereas prone position was applied to 3.75% of the patients. One-third of the patients received neuromuscular blockades. The median 7-day fluid balance was +6,600 mL. The mean PaO2/FiO2 ratio during the first 3 days, cumulative fluid balance on day 3, and average daily calories during the first week were independent predictors for adjusted 7-day mortality, whereas Acute Physiology and Chronic Health Evaluation (APACHE II) score, fluid balance on day 1, cumulative fluid balance, and average daily calories during the first week were independent predictors for adjusted 28-day mortality. Conclusions The 28-day mortality of ARDS was high. In addition, TV and fluid balance were greater than protective limits. These findings indicated the potential improvement of ARDS outcomes in our hospital.

Clinical epidemiology and mortality on patients with acute respiratory distress syndrome (ARDS) in Vietnam.

BackgroundThe clinical epidemiology and disease prognosis in patients with acute respiratory distress syndrome (ARDS) have not yet been fully elucidated in Vietnam.MethodsWe conducted a retrospective observational study at a national tertiary hospital in Hanoi, Vietnam. Participants were adult patients (age ≥18 years) who were admitted and diagnosed with ARDS during 2015–2017. Data on patients’ general and clinical conditions, radiographic findings, ventilator settings, gas exchange, and treatment methods were collected and compared between survivors and non-survivors. Risk factors for mortality were assessed using logistic regression analysis.ResultsAmong 126 eligible patients with ARDS admitted to the central tertiary hospital in Vietnam, we observed high mortality (57.1%). Of the total patients, 91.3% were transferred from local hospitals with a diagnosis of severe pneumonia and then diagnosed with ARDS at the central hospital. At the time of admission, 53.2% of patients had severe ARDS, 37.3% had moderate ARDS, and 9.5% had mild ARDS. The mean (standard deviation) sequential organ failure assessment (SOFA) score was 9.5 (3.4) in non-survivors and 7.4 (3.4) in survivors (p = 0.002). Although there was no significant difference in PaO2/FiO2 on admission between non-survivors and survivors, that on day 3 after admission was significantly different (p = 0.002). Logistic regression revealed that PaO2/FiO2 on day 3 [odds ratio (OR), 1.010; 95% confidence interval (CI), 1.003–1.017], length of stay in a local hospital before admission to the central hospital (OR, 1.122; 95% CI, 1.042–1.210) due to stable condition, and SOFA score on Day 1 (OR, 0.842; 95% CI, 0.708–1.002) were independent factors in patient survival.ConclusionsPatients with ARDS admitted the central tertiary hospital had severe illness and high mortality. Most patients were transferred from local hospitals. Improvements in human, medical, and sociological resources in local will contribute to reducing the mortality of ARDS in Vietnam.

Partial liquid ventilation–induced mild hypothermia improves the lung function and alleviates the inflammatory response during acute respiratory distress syndrome in canines

Background Acute respiratory distress syndrome (ARDS), which is the severest form of pulmonary injury, is the leading cause of death in critical care. At present, the mortality remains high in ARDS. Partial liquid ventilation (PLV) using perfluorocarbon (PFC) has been proven to improve gas exchange and respiratory dynamics of the lungs during ARDS. However, PLV has not been shown to reduce the mortality of ARDS. Some studies have shown that mild hypothermia therapy can reduce lung injuries in animal models of ARDS by reducing inflammatory cytokine levels in lung tissues. However, hypothermia cannot produce a lung protection effect alone, and it may have a synergistic effect with other protective measures. To explore the possible role of PLV combined with mild hypothermia in the treatment of ARDS, in this study, we used PFC liquid ventilation to induce mild hypothermia in dogs suffering from ARDS and analyzed the effects of PFC liquid ventilation-induced mild hypothermia on the levels of inflammatory factors and lung histopathology in dogs with ARDS. The experimental dogs were randomly divided into conventional mechanical ventilation (CMV), normal temperature PFC liquid ventilation (NPLV), hypothermic PFC liquid ventilation (HPLV), and mechanical ventilation (MV) groups. After induction of ARDS, the CMV group was treated with CMV for respiratory support, the HPLV group was treated with PLV-induced mild hypothermia using 15 °C PFC and maintained the rectal temperature at 34–36 °C, the NPLV group was treated with PLV using 36 °C PFC and maintained the rectal temperature at 36–38 °C. The MV group served as the control group. Analyses of the pulmonary pathology, partial pressure of oxygen in the blood, and lung wet-dry weight ratio (W/T) of each dog revealed that PLV-induced mild hypothermia significantly increased the PaO2 values and attenuated lung injury, and there were no adverse effects on hemodynamics. Furthermore, treatment with PLV-induced mild hypothermia significantly increased the expression of the anti-inflammatory factor IL-10 in bronchoalveolar lavage fluid (BALF) and attenuated the expression of interleukin (IL-6) and tumor necrosis factor-α (TNF-α) in peripheral blood and in lung BALF. Moreover, the results showed that the expression of myeloperoxidase (MPO) and NF-κB p65 in lung tissues was significantly decreased by PLV-induced mild hypothermia compared with NPLV and CMV. Our results indicated that PLV combined with mild hypothermia can provide protection against oleic acid-induced ARDS in dogs.

Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality.

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

Pediatric Acute Respiratory Distress Syndrome Mortality in the 21st Century: Nature, Nurture, Location, and?*

Pediatric Acute Respiratory Distress Syndrome Mortality in the 21st Century: Nature, Nurture, Location, and?*

Association between age and acute respiratory distress syndrome development and mortality following trauma.

Improved understanding of the relationship between patient age and acute respiratory distress syndrome (ARDS) development and mortality following traumatic injury may help facilitate generation of new hypotheses about ARDS pathophysiology and the role of novel treatments to improve outcomes across the age spectrum. We conducted a retrospective cohort study of trauma patients included in the National Trauma Data Bank who were admitted to an intensive care unit from 2007 to 2016. We determined ARDS incidence and mortality across eight age groups for the entire 10-year study period and by year. We used generalized linear Poisson regression models adjusted for underlying mortality risk (injury mechanism, Injury Severity Score, admission Glasgow Coma Scale score, admission heart rate, and admission hypotension). Acute respiratory distress syndrome occurred in 3.1% of 1,297,190 trauma encounters. Acute respiratory distress syndrome incidence was lowest among pediatric patients and highest among adults aged 35 to 64 years. Acute respiratory distress syndrome mortality was highest among patients 80 years or older (43.9%), followed by 65 to 79 years (30.6%) and 4 years or younger (25.3%). The relative risk of mortality associated with ARDS was highest among the pediatric age groups, with an adjusted relative risk (aRR) of 2.06 (95% confidence interval [CI], 1.72-2.70) among patients 4 years or younger compared with an aRR of 1.51 (95% CI, 1.42-1.62) for the entire cohort. Acute respiratory distress syndrome mortality increased over the 10-year study period (aRR, 1.03 per year; 95% CI, 1.02-1.05 per year), whereas all-cause mortality decreased (aRR, 0.98 per year; 95% CI, 0.98-0.99 per year). While ARDS development following traumatic injury was most common in middle-aged adults, patients 4 years or younger and 65 years or older with ARDS experienced the highest burden of mortality. Children 4 years or younger were disproportionately affected by ARDS relative to their low underlying mortality following trauma that was not complicated by ARDS. Acute respiratory distress syndrome-associated mortality following trauma has worsened over the past decade, emphasizing the need for new prevention and treatment strategies. Prognostic/epidemiological study, level III.

Pulmonary Surfactant Preparations and Surfactant Therapy for ARDS in Surgical Intensive Care (a Literature Review)

Introduction.Despite the fact that clinical studies of pulmonary surfactants conducted over many years have demonstrated their efficacy for the treatment of acute respiratory distress syndrome (ARDS) which led to their approval for use inRussia andBelarus, only a few similar positive results have been achieved in other countries. This calls for an extensive literature review for intensive care professionals.Materials and methods.Using the data from 87 papers this review covers the composition, properties, methods of administration and delivery strategies of surfactant in the treatment and prevention of ARDS in patients with sepsis, severe complex injuries, inhalation injuries and a range of complications associated with thoracic and cardiovascular surgical procedures, massive blood transfusions, severe obstetric pathologies and the A/H1N1 pneumonia.Results.The early administration of natural pulmonary surfactants within 24 hours following the onset of ARDS as a part of the ARDS combination treatment or prevention drives down the time on mechanical ventilation to six days or shorter, prevents ventilator-associated and hospital-acquired pneumonias, bringing the respiratory failure mortality rate down to 15–20%.Discussion.Offering the first attempt to discuss the causes of failure of Phase III multicenter clinical trials outsideRussia andBelarus, this review outlines recent developments in synthetic and powdered pulmonary surfactant preparations.Conclusion. Pulmonary surfactants are highly effective as a part of complex therapy in ARDS treatment and prevention, resulting in two to four fold drop in ARDS mortality rate. The timing of administration is seen as the key factor of the efficacy of surfactant therapy, explaining the differences in clinical trials results from different countries.

Bronchoalveolar fluid and plasma inflammatory biomarkers in contemporary ARDS patients

Purpose: Bronchoalveolar fluid (BALF) and plasma biomarkers are often endpoints in early phase randomized trials (RCTs) in acute respiratory distress syndrome (ARDS). With ARDS mortality decreasing, we analyzed baseline biomarkers in samples from contemporary ARDS patients participating in a prior RCT and compared these to historical controls.Materials and methods: Ninety ARDS adult patients enrolled in the parent trial. BALF and blood were collected at baseline, day 4 ± 1, and day 8 ± 1. Interleukins-8/-6/-1β/-1 receptor antagonist/-10; granulocyte colony stimulating factor; monocyte chemotactic protein-1; tumour necrosis factor-α; surfactant protein-D; von Willebrand factor; leukotriene B4; receptor for advanced glycosylation end products; soluble Fas ligand; and neutrophil counts were measured.Results: Compared to historical measurements, our values were generally substantially lower, despite our participants being similar to historical controls. For example, our BALF IL-8 and plasma IL-6 were notably lower than in a 1999 RCT of low tidal volume ventilation and a 2007 biomarker study, respectively.Conclusions: Baseline biomarker levels in current ARDS patients are substantially lower than 6–20 years before collection of these samples. These findings, whether from ICU care changes resulting in less inflammation or from variation in assay techniques over time, have important implications for design of future RCTs with biomarkers as endpoints.

Distinct Metabolic Endotype Mirroring Acute Respiratory Distress Syndrome (ARDS) Subphenotype and its Heterogeneous Biology

Predisposing aetiologies in Acute Respiratory Distress Syndrome (ARDS), perpetuates to heterogeneous clinical course hampering therapeutic response. Therefore, physiological variables need to be identified by stratifying ARDS subphenotypes and endotype, to target ARDS heterogeneity. The present study is stimulated by the fact that the ARDS heterogeneity arises from diverse pathophysiological changes leading to distinct ARDS endotypes characterized by perturbed biological mechanism which can be exploited in terms of metabolic profile by metabolomics. Biological endotypes using (n = 464 patients and controls), mBALF and serum samples were identified by high – resolution NMR spectroscopy from two clinically diagnosed ARDS subtypes grouped under mild, moderate and severe ARDS as subphenotype1and pulmonary and extra – pulmonary ARDS as subphenotype2. The identified mBALF endotypes (isoleucine, leucine, valine, lysine/arginine, tyrosine, threonine) and serum endotypes (proline, glutamate, phenylalanine, valine) in both subphenotypes by statistical analysis were tested for their reproducibility and robustness. By combining metabolic endotypes with clinical based mortality score (APACHE and SOFA) added to their predictive performance as ARDS mortality predictors. Thus, a comprehensive set of mBALF endotypes representing compartmentalized lung milieu and serological endotypes representing systemic markers of ARDS subtypes were validated. The interlinked biological pathway of these disease specific endotype further elucidated their role as candidate biomarker in governing ARDS heterogeneous biology.

Lung fluid biomarkers for acute respiratory distress syndrome: a systematic review and meta-analysis

BackgroundWith the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in pulmonary disease diagnosis. We aimed to review and summarize lung fluid biomarkers associated with acute respiratory distress syndrome diagnosis and mortality.MethodsAfter searching PubMed, Embase, Web of Science, and the Cochrane Library for articles published prior to January 11, 2018, we performed a meta-analysis on biomarkers for acute respiratory distress syndrome diagnosis in at-risk patients and those related to disease mortality. From the included studies, we then extracted the mean and standard deviation of the biomarker concentrations measured in the lung fluid, acute respiratory distress syndrome etiologies, sample size, demographic variables, diagnostic criteria, mortality, and protocol for obtaining the lung fluid. The effect size was measured by the ratio of means, which was then synthesized by the inverse-variance method using its natural logarithm form and transformed to obtain a pooled ratio and 95% confidence interval.ResultsIn total, 1156 articles were identified, and 49 studies were included. Increases in total phospholipases A2 activity, total protein, albumin, plasminogen activator inhibitor-1, soluble receptor for advanced glycation end products, and platelet activating factor-acetyl choline were most strongly associated with acute respiratory distress syndrome diagnosis. As for biomarkers associated with acute respiratory distress syndrome mortality, interleukin-1β, interleukin-6, interleukin-8, Kerbs von Lungren-6, and plasminogen activator inhibitor-1 were significantly increased in the lung fluid of patients who died. Decreased levels of Club cell protein and matrix metalloproteinases-9 were associated with increased odds for acute respiratory distress syndrome diagnosis, whereas decreased levels of Club cell protein and interleukin-2 were associated with increased odds for acute respiratory distress syndrome mortality.ConclusionsThis meta-analysis provides a ranking system for lung fluid biomarkers, according to their association with diagnosis or mortality of acute respiratory distress syndrome. The performance of biomarkers among studies shown in this article may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.

Morbidity and Mortality Among Critically Injured Children With Acute Respiratory Distress Syndrome.

To evaluate morbidity and mortality among critically injured children with acute respiratory distress syndrome. Retrospective cohort study. Four-hundred sixty Level I/II adult or pediatric trauma centers contributing to the National Trauma Data Bank. One hundred forty-six thousand fifty-eight patients less than 18 years old admitted to an ICU with traumatic injury from 2007 to 2016. None. We assessed in-hospital mortality and need for postdischarge care among patients with and without acute respiratory distress syndrome and hospital resource utilization and discharge disposition among survivors. Analyses were adjusted for underlying mortality risk (age, Injury Severity Score, serious brain or chest injury, and admission heart rate and hypotension) and year, transfer status, and facility trauma level designation. Acute respiratory distress syndrome occurred in 2,590 patients (1.8%). Mortality was 20.0% among acute respiratory distress syndrome patients versus 4.3% among nonacute respiratory distress syndrome patients, with an adjusted relative risk of 1.76 (95% CI, 1.52-2.04). Postdischarge care was required in an additional 44.8% of acute respiratory distress syndrome patients versus 16.0% of patients without acute respiratory distress syndrome (adjusted relative risk, 3.59; 2.87-4.49), with only 35.1% of acute respiratory distress syndrome patients discharging to home versus 79.8% of patients without acute respiratory distress syndrome. Acute respiratory distress syndrome mortality did not change over the 10-year study period (adjusted relative risk, 1.01/yr; 0.96-1.06) nor did the proportion of acute respiratory distress syndrome patients requiring postdischarge care (adjusted relative risk, 1.04/yr; 0.97-1.11). Duration of ventilation, ICU stay, and hospital stay were all significantly longer among acute respiratory distress syndrome survivors. Tracheostomy placement occurred in 18.4% of acute respiratory distress syndrome survivors versus 2.1% of patients without acute respiratory distress syndrome (adjusted relative risk, 3.10; 2.59-3.70). Acute respiratory distress syndrome development following traumatic injury in children is associated with significantly increased risk of morbidity and mortality, even after adjustment for injury severity and hemodynamic abnormalities. Outcomes have not improved over the past decade, emphasizing the need for new therapeutic interventions, and prevention strategies for acute respiratory distress syndrome among severely injured children.

Deconstructing ARDS Variability: Platelet Count, an ARDS Intermediate Phenotype and Novel Mediator of Genetic Effects in ARDS.

Genome-wide association studies (GWASs) in acute respiratory distress syndrome (ARDS) have been hampered by the heterogeneity of the clinical phenotypes and the large sample size requirement. As the limitations of these studies to uncover the complex genetic architecture of ARDS are evident, new approaches intended to reduce data complexity need to be applied. Intermediate phenotypes are mechanism-related manifestations of the disease, located closer to the genetic substrate than to disease phenotype, and therefore able to reflect more directly and more strongly the effect of causal genes. The dissection of complex phenotypes into less complex intermediate phenotypes is a valuable strategy to facilitate the discovery of those genetic variants whose effect is not strong enough to be detected as markers of disease in traditional GWASs. Genetic causal inference methodologies can be then applied to estimate the implication of the intermediate trait in the causal circuit between genes and disease. By following this strategy, platelet count, a relevant intermediate quantitative trait in ARDS, has been recently identified as a novel mediator in the genetic contribution to ARDS risk and mortality. The use of intermediate phenotypes and causal inference are emerging methodological and statistical strategies that can help to overcome the limitations of traditional GWASs in ARDS. Moreover, these approaches can provide evidence for the mechanisms linking genes to ARDS and help to prioritize therapeutic targets for the treatment of this devastating syndrome.

Acute respiratory distress-syndrome in the general complications of severe acute pancreatitis.

Backgrounds/AimsImprovement of efficiency of treatment of patients with severe acute pancreatitis (SAP), complicated by acute respiratory distress-syndrome (ARDS).MethodsThe retrospective research of 67 SAP patients treated at the ICU of the NSSPCS has been conducted from 2008 to 2017. The basic criterion of patient inclusion was stable respiration impairment leading to hypoxia with PaO2/FiO2<300 mmHg that required mechanical ventilatory support.ResultsPancreatitis-associated ARDS was diagnosed in 36 cases (53.7%). The most frequent clinical form (15 cases) was ARDS of moderate severity (41.5%). The total mortality due to pancreatitis-associated ARDS made 44.5%. Close relationship between ARDS severity and mortality was evident. All lethal outcomes occurred due to progressing multiple organ dysfunction. No deaths were caused by uncontrollable hypoxemia.ConclusionsThe research has confirmed the leading role of pancreatitis-associated ARDS in development and high mortality rate of multiple organ dysfunction syndrome in SAP. Early recognition of the complication and application of ventilatory support techniques resulted in fast restoration of oxygenation and improvement of treatment efficiency.