Extrapulmonary Acute Respiratory Distress Syndrome Research Articles

Lactobacillus rhamnosus (LR) ameliorates pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS) via targeting neutrophils

Pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure associated with high mortality. Despite progress in our understanding of the pathological mechanism causing the crippling illness, there are currently no targeted pharmaceutical treatments available for it. Recent discoveries have emphasized the existence of a potential nexus between gut and lung health fueling novel approaches including probiotics for the treatment of ARDS. We thus investigated the prophylactic-potential of Lactobacillus rhamnosus-(LR) in lipopolysaccharide (LPS)-induced pulmonary and cecal ligation puncture (CLP) induced extrapulmonary ARDS mice. Our in-vivo findings revealed that pretreatment with LR significantly ameliorated vascular-permeability (edema) of the lungs via modulating the neutrophils along with significantly reducing the expression of inflammatory-cytokines in the BALF, lungs and serum in both pulmonary and extrapulmonary mice-models. Interestingly, our ex-vivo immunofluorescence and flow cytometric data suggested that mechanistically LR via short chain fatty acids (butyrate being the most potent and efficient in ameliorating the pathophysiology of both pulmonary and extra-pulmonary ARDS) targets the phagocytic and neutrophils extracellular traps (NETs) releasing potential of neutrophils. Moreover, our in-vivo data further corroborated our ex-vivo findings and suggested that butyrate exhibits enhanced potential in ameliorating the pathophysiology of ARDS via reducing the infiltration of neutrophils into the lungs. Altogether, our study establishes the prophylactic role of LR and its associated metabolites in the prevention and management of both pulmonary and extrapulmonary ARDS via targeting neutrophils.

Expression and significance of serum KL-6 in patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a common and serious complication that occurs in the ICU. the determination of early ARDS indicators, along with timely treatment, can potentially diminish medical costs and reduce ARDS-related mortality. In this report, we evaluated the clinical significance of circulating Krebs von den Lungen-6 (KL-6) content among patients with intra- and extrapulmonary ARDS to investigate the clinical significance of serum KL-6. Patients who met the ARDS Berlin criteria and were hospitalized in the intensive care unit of the China-Japan Union Hospital of Jilin University between September 2021 and September 2022 were recruited for analysis. ARDS patients were divided into an intrapulmonary ARDS group (n=23) and an extrapulmonary ARDS group (n=27) based on their primary diagnosis. Baseline demographic data, including age and sex, and clinical data, including underlying diseases and mortality, of the two groups were collected and analyzed. Peripheral venous blood was collected on Day 0 (baseline), Day 1, Day 3, and Day 7. The kinetic levels of serum KL-6 were compared between patients who survived and those who died within one week of ARDS diagnosis. The prognosis, survival times, and status of patients within 28 days after diagnosis were evaluated. In the intrapulmonary ARDS group, patients who died had significantly higher serum KL-6 levels in the seven days following diagnosis than those who survived. In contrast, in the extrapulmonary group, the difference in KL-6 values between patients who survived and died was only significant on the first day after diagnosis. The peak levels of serum KL-6 in the death group were significantly higher than those in the survival group for both intra- and extrapulmonary ARDS (P=0.0253). The optimal cutoff value of the serum KL-6 level was 1,452.3 U/mL in intrapulmonary ARDS patients and 828.2 U/mL in extrapulmonary patients. Serum KL-6 levels higher than the cutoff levels were confirmed to be a significant prognostic predictor of poor survival within 28 days of diagnosis in patients with intra- and extrapulmonary ARDS. The serum KL-6 level is potentially a good indicator for predicting the prognosis of patients with ARDS.

Evaluation of Patients with Acute Respiratory Distress Syndrome Followed on Mechanical Ventilator in a Tertiary Pediatric Intensive Care and the Factors That May Be Associated with Death in These Patients.

We aimed to evaluate the clinical, demographic, and laboratory characteristics of the patients followed up with pediatric acute respiratory distress syndrome in our pediatric intensive care unit and to determine the factors that have an effect on the outcomes. The medical records of 40 patients with acute respiratory distress syndrome who were followed up on mechanical ventilators in the pediatric intensive care unit of Adıyaman University were retrospectively scanned. From the medical records, the demographic data, clinical features, and laboratory characteristics were recorded. Eighteen of the patients were female and 22 were male. The mean age was 45.25 ± 56.63 months. A total of 27 (67.5%) of the patients were classified as pulmonary and 13 (32.5%) as extrapulmonary acute respiratory distress syndrome. Sixteen (40%) patients were followed in pressure-controlled mode only, 2 (5%) patients in volume-controlled mode only, and 22 (55%) patients in alternate modes. A total of 17 (42.5%) patients died. The median pediatric index of mortality, pediatric index of mortality-II, pediatric risk of mortality, and pediatric logistic organ dysfunction score values of the surviving patients were significantly lower than the dead patients. Median aspartate aminotransferase (P = .003) and lactate dehydrogenase (P = .008) values were found to be significantly higher in patients who died, while median pH values (P = .049) were found to be lower. The median length of stay in pediatric intensive care unit and duration of mechanical ventilators were significantly shorter in patients who died. Also, the median pediatric index of mortality, pediatric index of mortality-II, pediatric risk of mortality, and pediatric logistic organ dysfunction values of pulmonary acute respiratory distress syndrome patients were significantly lower than those of extrapulmonary acute respiratory distress syndrome patients. Despite advances in follow-up and management, mortality due to acute respiratory distress syndrome is still high. Mechanical ventilator duration, length of stay in pediatric intensive care unit, some mechanical ventilator parameters, mortality scores, and laboratory tests were associated with mortality. Alternatively, mechanical ventilator applications may reduce mortality rates.

Whole pulmonary assessment 1 year after paediatric acute respiratory distress syndrome: prospective multicentre study

BackgroundLong-term pulmonary sequelae, including 1-year thoracic computed tomography (CT) sequelae of paediatric acute respiratory distress syndrome (ARDS) remain unknown. The purpose of the study was to determine pulmonary abnormalities in child survivors of pulmonary (p-ARDS) and extra-pulmonary ARDS (ep-ARDS) 1 year after paediatric intensive care unit discharge (PICUD).MethodsProspective multicentre study in four paediatric academic centres between 2005 and 2014. Patients with ARDS were assessed 1 year after PICUD with respiratory symptom questionnaire, thoracic CT and pulmonary function tests (PFT).Results39 patients (31 p-ARDS) aged 1.1–16.2 years were assessed. Respiratory symptoms at rest or exercise and/or respiratory maintenance treatment were reported in 23 (74%) of children with p-ARDS but in 1 (13%) of those with ep-ARDS. Thoracic CT abnormalities were observed in 18 (60%) of children with p-ARDS and 4 (50%) of those with ep-ARDS. Diffuse and more important CT abnormalities, such as ground glass opacities or mosaic perfusion patterns, were observed in 5 (13%) of children, all with p-ARDS. PFT abnormalities were observed in 30 (86%) of patients: lung hyperinflation and/or obstructive pattern in 12 (34%) children, restrictive abnormalities in 6 (50%), mild decrease in diffusing capacity in 2 (38%) and 6-min walking distance decrease in 11 (73%). Important PFT abnormalities were observed in 7 (20%) children, all with p-ARDS. Increasing driving pressure (max plateau pressure—max positive end-expiratory pressure) was correlated with increasing CT-scan abnormalities and increasing functional residual capacity (more hyperinflation) (p < 0.005).ConclusionsChildren surviving ARDS requiring mechanical ventilation present frequent respiratory symptoms, significant CT-scan and PFT abnormalities 1 year after PICUD. This highlights the need for a systematic pulmonary assessment of these children.Trial registration The study was registered on Clinical Trials.gov PRS (ID NCT01435889)

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.

Prevalence, risk, and outcome of deep vein thrombosis in acute respiratory distress syndrome

BackgroundFew data exist on deep vein thrombosis (DVT) in patients with acute respiratory distress syndrome (ARDS), a group of heterogeneous diseases characterized by acute hypoxemia.Study design and methodsWe retrospectively enrolled 225 adults with ARDS admitted to the Beijing Chao-Yang Hospital and the First Affiliated Hospital of Shandong First Medical University between 1 January 2015 and 30 June 2020. We analyzed clinical, laboratory, and echocardiography data for groups with and without DVT and for direct (pulmonary) and indirect (extrapulmonary) ARDS subgroups.ResultsNinety (40.0%) patients developed DVT. Compared with the non-DVT group, patients with DVT were older, had lower serum creatinine levels, lower partial pressure of arterial oxygen/fraction of inspired oxygen, higher serum procalcitonin levels, higher Padua prediction scores, and higher proportions of sedation and invasive mechanical ventilation (IMV). Multivariate analysis showed an association between age, serum creatinine level, IMV, and DVT in the ARDS cohort. The sensitivity and specificity of corresponding receiver operating characteristic curves were not inferior to those of the Padua prediction score and the Caprini score for screening for DVT in the three ARDS cohorts. Patients with DVT had a significantly lower survival rate than those without DVT in the overall ARDS cohort and in the groups with direct and indirect ARDS.ConclusionsThe prevalence of DVT is high in patients with ARDS. The risk factors for DVT are age, serum creatinine level, and IMV. DVT is associated with decreased survival in patients with ARDS.

An assessment of esophageal balloon use for the titration of airway pressure release ventilation and controlled mechanical ventilation in a patient with extrapulmonary acute respiratory distress syndrome: a case report

BackgroundEsophageal pressure measurement is a minimally invasive monitoring process that assesses respiratory mechanics in patients with acute respiratory distress syndrome. Airway pressure release ventilation is a relatively new positive pressure ventilation modality, characterized by a series of advantages in patients with acute respiratory distress syndrome.Case presentationWe report a case of a 55-year-old chilean female, with preexisting hypertension and recurrent renal colic who entered the cardiosurgical intensive care unit with signs and symptoms of urinary sepsis secondary to a right-sided obstructive urolithiasis. At the time of admission, the patient showed signs of urinary sepsis, a poor overall condition, hemodynamic instability, tachycardia, hypotension, and needed vasoactive drugs. Initially the patient was treated with volume control ventilation. Then, ventilation was with conventional ventilation parameters described by the Acute Respiratory Distress Syndrome Network. However, hemodynamic complications led to reduced airway pressure. Later she presented intraabdominal hypertension that compromised the oxygen supply and her ventilation management. Considering these records, an esophageal manometry was used to measure distending lung pressure, that is, transpulmonary pressure, to protect lungs. Initial use of the esophageal balloon was in a volume-controlled modality (deep sedation), which allowed the medical team to perform inspiratory and expiratory pause maneuvers to monitor transpulmonary plateau pressure as a substitute for pulmonary distension and expiratory pause and determine transpulmonary positive end-expiratory pressure. On the third day of mechanical respiration, the modality was switched to airway pressure release ventilation. The use of airway pressure release ventilation was associated with reduced hemodynamic complications and kept transpulmonary pressure between 0 and 20 cmH2O despite a sustained high positive end-expiratory pressure of 20 cmH2O.ConclusionThe application of this technique is shown in airway pressure release ventilation with spontaneous ventilation, which is then compared with a controlled modality that requires a lesser number of sedative doses and vasoactive drugs, without altering the criteria for lung protection as guided by esophageal manometry.

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.

Significance of monitoring pulmonary arterial pressure and cardiac function in neonates with pulmonary or extra-pulmonary acute respiratory distress syndrome

To evaluate the dynamic changes of pulmonary arterial pressure (PAP) and cardiac function in neonates with pulmonary or extra-pulmonary acute respiratory distress syndrome (ARDSp/ARDSexp). An observational study was conducted. A total of 128 neonates with ARDS admitted to neonatology department of the Affiliated Yancheng Hospital of Southeast University Medical College from January 2016 to December 2020 were enrolled, with 67 neonates in ARDSp group and 61 neonates in ARDSexp group. After starting mechanical ventilation, oxygenation index [OI, OI = mean airway pressure (Pmean)×fraction of inspired oxygen (FiO2)/arterial partial pressure of oxygen (PaO2)×100], PAP, cardiac function parameters [cardiac index (CI), left ventricular ejection fraction (LVEF), right ventricular Tei (RV-Tei)], and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) were compared between the two groups; the incidence of pulmonary arterial hypertension [PAH, pulmonary artery systolic pressure (PASP) was more than 35 mmHg (1 mmHg = 0.133 kPa) or more than 2/3 of the systolic blood pressure of the body circulation] of neonates was recorded. The correlation between PAP and NT-proBNP was analyzed by Pearson correlation method. The dynamically changes in PAP and RV-Tei before and after using Milrinone in neonates with ARDSp and ARDSexp combined with moderate-severe PAH (PASP 50-69 mmHg was moderate, and PASP ≥ 70 mmHg was severe) were observed. The duration of mechanical ventilation, total length of hospital stay and prognosis were recorded; Kaplan-Meier survival curve was drawn to analyze the 28-day survival of the two groups. The occurrence rate of PAH in ARDSp group was significantly higher than that in ARDSexp group (97.01% vs. 70.49%, P < 0.01). OI, PAP, NT-proBNP and RV-Tei were also higher [OI: 17.61±6.12 vs. 11.04±5.35, PAP (mmHg): 64.27±9.54 vs. 53.61±6.47, NT-proBNP (ng/L): 23 126.32±1 485.14 vs. 18 624.24±1 647.15, RV-Tei: 0.61±0.22 vs. 0.52±0.19, all P < 0.05], but there was no significant difference in CI or LVEF between the two groups. Pearson correlation analysis showed that PAP was significantly positively correlated with NT-proBNP (r = 0.918, P < 0.01). There were 97 ARDS neonates with moderate-severe PAH with 63 in ARDSp group and 34 in ARDSexp group. Both PAP and RV-Tei in the two group showed a decreasing trend with the prolongation of Milrinone treatment, the decrease was more significant in the ARDSexp group compared with ARDSp group, the difference was statistically significant at 72 hours of treatment [PAP (mmHg): 38.42±8.95 vs. 45.67±13.32, RV-Tei: 0.58±0.19 vs. 0.61±0.13, both P < 0.05]; there was no significant difference in PAP or RV-Tei before extubation between the two groups. The duration of mechanical ventilation and the total length of hospital stay in ARDSp group were significantly longer than those in ARDSexp group [duration of mechanical ventilation (days): 10.12±1.36 vs. 6.31±1.31, total length of hospital stay (days): 16.52±3.25 vs. 13.12±3.57, both P < 0.01]. Kaplan-Meier survival curve showed that neonate in ARDSp group had a significantly lower 28-day cumulative survival rate as compared with ARDSexp group (82.09% vs. 95.01%; Log-Rank test: χ2 = 5.062, P = 0.025). Both PAP and RV-Tei were significantly increased in neonates with ARDS, PAP in neonates with ARDSp were significantly higher than that in neonates with ARDSexp. Dynamic monitoring of PAP and RV-Tei can reflect the severity of ARDS in neonates, and targeted intervention of pulmonary surfactant combined with Milinone for improving oxygenation and reducing PAP is one of the effective methods for the treatment of PAH.

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study

BackgroundHeterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described.MethodsIn this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal–Wallis rank tests and Chi-squared tests were used to compare between-etiology differences.ResultsFrom 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia.ConclusionThis study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

Prognostic Value of Angiopoietin-like 4 in Patients with Acute Respiratory Distress Syndrome.

Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that plays an important role in endothelial injury and the inflammatory response. Experimental models have implicated ANGPTL4 in acute respiratory distress syndrome (ARDS), but its impact on the progression of ARDS is unclear. Paired bronchoalveolar lavage fluid (BALF) and serum samples were obtained from patients with ARDS (n = 56) within 24 h of diagnosis and from control subjects (n = 32). ANGPTL4, angiopoietin-2, interleukin (IL)-6, and TNF-α levels were measured by magnetic Luminex assay. BALF albumin (BA) and serum albumin (SA) were evaluated by enzyme-linked immunosorbent assay. BALF and serum ANGPTL4 concentrations were higher in patients with ARDS than in controls and were even higher in non-survivors than in survivors. The serum ANGPTL4 level was higher in indirect (extrapulmonary) ARDS than in direct (pulmonary) ARDS. Furthermore, BALF and serum ANGPTL4 levels correlated well with angiopoietin-2, IL-6, and TNF-α levels in BALF and serum. BALF ANGPTL4 was positively correlated with the BA/SA ratio (an indicator of pulmonary vascular permeability), and serum ANGPTL4 was associated with the severity of multiple organ dysfunction syndrome based on SOFA and APACHE II scores. Moreover, serum ANGPTL4 was better able to predict 28-day ARDS-related mortality (AUC 0.746, P < 0.01) than the APACHE II score or PaO2/FiO2 ratio. Serum ANGPTL4 was identified as an independent risk factor for mortality in a univariate Cox regression model (P < 0.001). ANGPTL4 levels were elevated in patients with ARDS and significantly correlated with disease severity and mortality. ANGPTL4 may be a novel prognostic biomarker in ARDS.

Gut-lymph-lung pathway mediates sepsis-induced acute lung injury.

This review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of “gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome.” Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.

Effect of positive end-expiratory pressure on functional residual capacity in two experimental models of acute respiratory distress syndrome.

ObjectiveMeasurement of positive end-expiratory pressure (PEEP)-induced recruitment lung volume using passive spirometry is based on the assumption that the functional residual capacity (FRC) is not modified by the PEEP changes. We aimed to investigate the influence of PEEP on FRC in different models of acute respiratory distress syndrome (ARDS).MethodsA randomized crossover study was performed in 12 pigs. Pulmonary (n = 6) and extra-pulmonary (n = 6) ARDS models were established using an alveolar instillation of hydrochloric acid and a right atrium injection of oleic acid, respectively. Low (5 cmH2O) and high (15 cmH2O) PEEP were randomly applied in each animal. FRC and recruitment volume were determined using the nitrogen wash-in/wash-out technique and release maneuver.ResultsFRC was not significantly different between the two PEEP levels in either pulmonary ARDS (299 ± 92 mL and 309 ± 130 mL at 5 and 15 cmH2O, respectively) or extra-pulmonary ARDS (305 ± 143 mL and 328 ± 197 mL at 5 and 15 cmH2O, respectively). The recruitment volume was not significantly different between the two models (pulmonary, 341 ± 100 mL; extra-pulmonary, 351 ± 170 mL).ConclusionsPEEP did not influence FRC in either the pulmonary or extra-pulmonary ARDS pig model.

Pulmonary versus Extrapulmonary Acute Respiratory Distress Syndrome: Clinical Characteristics and Outcome

Abstract Background: Acute respiratory distress syndrome is a clinical syndrome characterized by a refractory hypoxemia due to an inflammatory and high permeability pulmonary edema secondary to direct or indirect lung insult (pulmonary and extrapulmonary form). These two categories of ARDS patients are different regarding the respiratory mechanics, lung recruitment, gas exchange, and positive end-expiratory pressure response. Aim of Study: The aim of this work was to compare the clinical characteristics and outcomes between the two major ARDS subtypes; pulmonary and extrapulmonary. Patients and Methods: A prospective study was conducted during the period from July 2014 to January 2016 in Intensive Care Unit, El-Hussein University Hospital. It included 60 patients diagnosed as ARDS. They were subclassified into pulmonary and extrapulmonary ARDS groups according to the cause of lung injury. Both groups were compared regarding the clinical features, response to treatment and clinical outcome. Results: Patients with extrapulmonary ARDS developed more deteriorated liver and renal functions and arterial blood gases with a better response to elevated levels of PEEP and vasopressors with a mortality rate of 75%. In patients with pulmonary ARDS, mild organs dysfunction were developed with a better response to low levels of PEEP and a mortality rate of 25%. Conclusion: Subdivision of ARDS into pulmonary and extrapulmonary categories has worthy effect on both treatment and clinical outcome. Additionally, they are different in the degree of organ dysfunction and severity of clinical pictures. Recommendation: Proper assessment of patients with ARDS at admission to put them within a major category whether pulmonary or extrapulmonary ARDS. This simple classification will help physician to decide on treatment and to predict prognosis.

Aetiology and Short-Term Outcome of Acute Respiratory Distress Syndrome: A Real-World Experience from a Medical Intensive Care Unit in Southern India

Background Acute respiratory distress syndrome (ARDS) is a highly fatal syndrome especially in resource constrained settings. In this study we prospectively studied the aetiology of ARDS and its short-term outcome. Methods Consecutive adults with suspected ARDS were screened. ARDS was diagnosed by the Berlin criteria. Aetiology was determined clinically, and by imaging and microbiological investigations. Patients presenting with fever, prominent cough and expectoration had a throat swab tested for influenza H1N1 virus. Outcome was discharge from hospital or death. Results A total of 42 patients, mean age 42.6 years, were studied. All received mechanical ventilation. Thirteen (31%) had pulmonary ARDS: H1N1 virus infection (n = 5), pneumonia (n = 7) and tuberculosis (n = 1). Twenty nine (69%) had extrapulmonary ARDS: sepsis (n = 16) and scrub typhus (n = 8). Thirty three (79%) died, of the nine survivors scrub typhus was diagnosed in seven patients. Conclusion The aetiology of ARDS in tropical medical setting is infection related. ARDS due to scrub typhus appeared to be mild with good outcome.

Outcome Comparison Between Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome in Pediatric Intensive Care Unit

Acute respiratory distress syndrome (ARDS) is a lung disease characterized by severe diffuse inflammation and hypoxemia. The cause of ARDS can be pulmonary or extrapulmonary originated. The outcome of pulmonary and extrapulmonary pediatric ARDS are poorly described. The objective of this study was to determine the outcome differences between pulmonary and extrapulmonary pediatric ARDS. A retrospective study was carried out in 60 patients who admitted to the Pediatric Intensive Care Unit (PICU), Sanglah Hospital, between January 2018 until December 2019. All children aged 0-18 years old diagnosed with ARDS according to Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria were included in this study. Length of ventilation, ventilator-free days, PICU length of stay, and PICU mortality as the outcome of this study were obtained from medical records. Statistical analysis was done using Chi-square and Mann-Whitney test. Most of the patients were supported by invasive ventilation with the severity of ARDS was mild to moderate. The underlying disease of pulmonary ARDS (ARDSp) was pneumonia (100%), whereas in extrapulmonary ARDS (ARDSexp) was sepsis (100%). Analysis of outcome showed significant difference in mortality (33.3% vs 73.3%, p=0.002). The mortality was higher among those in the moderate severity of oxygenation index (64.5%, p=0.001). No significant difference was found in length of ventilation and PICU length of stay. The ventilator-free days in ARDSp was higher (22 days vs 0 days, p=0.000) compared with the ARDSexp. This study concluded that patients with extrapulmonary ARDS had poorer outcomes (higher mortality and less ventilator-free day) compared with pulmonary ARDS. The severity of ARDS based on the oxygenation index measurement can be used to discriminate mortality.

Serial changes in biomarkers in pulmonary and extrapulmonary acute respiratory distress syndrome

Objective: To compare the serial changes of circulating angiopoietin-2 (Ang-2), surfactant protein D (SP-D) and soluble receptor for advanced glycation end product (sRAGE) in patients with pulmonary acute respiratory distress syndrome (ARDS) and extrapulmonary ARDS. Methods: A total of 36 eligible patients with ARDS were included from the Department of Respiratory Intensive Care Unit(RCU) and Department of Intensive Care Unit (ICU), the Central Hospital of Wuhan, during April 2017 to February 2018, and divided into pulmonary ARDS group (n=20) and extrapulmonary ARDS group (n=16) according to primary causes. The levels of Ang-2, SP-D and sRAGE in serum of each group were measured on Day 1, 4 and 7 after diagnosis. Results: The serum level of Ang-2 in extrapulmonary ARDS group declined gradually during the course. The serum level of Ang-2 on Day 1 was significantly higher than that on Day 7 [2 801 (1 386, 7 526) vs 1 461 (737, 2 135) ng/L, P<0.05]. There was no significant difference in serum levels of Ang-2 on Day 1, 4, 7 in pulmonary ARDS group [1 462 (545, 3 715) vs 1 353 (659, 5 847) vs1 616 (754, 3 460) ng/L, all P>0.05]. There was no significant difference in serum levels of SP-D on Day 1,4, 7 in each group [pulmonary ARDS group: 5.6(1.8, 14.0) vs 5.7(1.8, 14.5) vs 7.9(3.0, 16.8) mg/L, all P>0.05; extrapulmonary ARDS group: 3.4(0.5, 9.1) vs 1.6(0.6, 6.3) vs 1.6(0.7, 7.9)mg/L, all P>0.05]. The serum level of sRAGE in each group declined gradually during the course. The serum level of sRAGE on Day 1 in each group was significantly higher than that on Day 7 [pulmonary ARDS group: 328(107, 595) vs 66 (50,171) ng/L, extrapulmonary ARDS group: 237 (98, 410) vs 81 (38, 154) ng/L, all P<0.05]. Conclusion: The serum level of Ang-2 in extrapulmonary ARDS declines significantly in the early stage of disease, while there is no significant difference in that of pulmonary ARDS.

Mesenchymal Stromal Cells Are More Effective Than Their Extracellular Vesicles at Reducing Lung Injury Regardless of Acute Respiratory Distress Syndrome Etiology.

Although mesenchymal stromal cells (MSCs) have demonstrated beneficial effects on experimental acute respiratory distress syndrome (ARDS), preconditioning may be required to potentiate their therapeutic effects. Additionally, administration of cell-free products, such as extracellular vesicles (EVs) obtained from MSC-conditioned media, might be as effective as MSCs. In this study, we comparatively evaluated the effects of MSCs, preconditioned or not with serum collected from mice with pulmonary or extrapulmonary ARDS (ARDSp and ARDSexp, respectively), and the EVs derived from these cells on lung inflammation and remodeling in ARDSp and ARDSexp mice. Administration of MSCs (preconditioned or not), but not their EVs, reduced static lung elastance, interstitial edema, and collagen fiber content in both ARDSp and ARDSexp. Although MSCs and EVs reduced alveolar collapse and neutrophil cell counts in lung tissue, therapeutic responses were superior in mice receiving MSCs, regardless of preconditioning. Despite higher total cell, macrophage, and neutrophil counts in bronchoalveolar lavage fluid in ARDSp than ARDSexp, MSCs and EVs (preconditioned or not) led to a similar decrease. In ARDSp, both MSCs and EVs, regardless of preconditioning, reduced levels of tumor necrosis factor- (TNF-) α, interleukin-6, keratinocyte chemoattractant (KC), vascular endothelial growth factor (VEGF), and transforming growth factor- (TGF-) β in lung homogenates. In ARDSexp, TNF-α, interleukin-6, and KC levels were reduced by MSCs and EVs, preconditioned or not; only MSCs reduced VEGF levels, while TGF-β levels were similarly increased in ARDSexp treated either with saline, MSCs, or EVs, regardless of preconditioning. In conclusion, MSCs yielded greater overall improvement in ARDS in comparison to EVs derived from the same number of cells and regardless of the preconditioning status. However, the effects of MSCs and EVs differed according to ARDS etiology.

Respiratory Mechanics, Lung Recruitability, and Gas Exchange in Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome is a clinical syndrome characterized by a refractory hypoxemia due to an inflammatory and high permeability pulmonary edema secondary to direct or indirect lung insult (pulmonary and extrapulmonary form). Aim of this study was to evaluate in a large database of acute respiratory distress syndrome patients, the pulmonary versus extrapulmonary form in terms of respiratory mechanics, lung recruitment, gas exchange, and positive end-expiratory pressure response. A secondary analysis of previously published data. One-hundred eighty-one sedated and paralyzed acute respiratory distress syndrome patients (age 60 yr [46-72 yr], body mass index 25 kg/m [22-28 kg/m], and PaO2/FIO2 184 ± 66). Lung CT scan performed at 5 and 45 cm H2O. Two levels of positive end-expiratory pressure (5 and 15 cm H2O) were randomly applied. Ninety-seven and 84 patients had a pulmonary and extrapulmonary acute respiratory distress syndrome. The median time from intensive care admission to the CT scan and respiratory mechanics analysis was 4 days (interquartile range, 2-6). At both positive end-expiratory pressure levels, pulmonary acute respiratory distress syndrome presented a significantly lower PaO2/FIO2 and higher physiologic dead space compared with extrapulmonary acute respiratory distress syndrome. The lung and chest wall elastance were similar between groups. The intra-abdominal pressure was significantly higher in extrapulmonary compared with pulmonary acute respiratory distress syndrome (10 mm Hg [7-12 mm Hg] vs 7 mm Hg [5-8 mm Hg]). The lung weight and lung recruitability were significantly higher in pulmonary acute respiratory distress syndrome (1,534 g [1,286-1,835 g] vs 1,342 g [1,090-1,507 g] and 16% [9-25%] vs 9% [5-14%]). In the early stage, pulmonary acute respiratory distress syndrome is characterized by a greater impairment of gas exchange and higher lung recruitability. The recognition of the origin of acute respiratory distress syndrome is important for a more customized ventilatory management.

The time-controlled adaptive ventilation protocol: mechanistic approach to reducing ventilator-induced lung injury.

Airway pressure release ventilation (APRV) is a ventilator mode that has previously been considered a rescue mode, but has gained acceptance as a primary mode of ventilation. In clinical series and experimental animal models of extrapulmonary acute respiratory distress syndrome (ARDS), the early application of APRV was able to prevent the development of ARDS. Recent experimental evidence has suggested mechanisms by which APRV, using the time-controlled adaptive ventilation (TCAV) protocol, may reduce lung injury, including: 1) an improvement in alveolar recruitment and homogeneity; 2) reduction in alveolar and alveolar duct micro-strain and stress-risers; 3) reduction in alveolar tidal volumes; and 4) recruitment of the chest wall by combating increased intra-abdominal pressure. This review examines these studies and discusses our current understanding of the pleiotropic mechanisms by which TCAV protects the lung. APRV set according to the TCAV protocol has been misunderstood and this review serves to highlight the various protective physiological and mechanical effects it has on the lung, so that its clinical application may be broadened.