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OBJECTIVE: To compare two methods for defining and classifying the severity of pediatric acute respiratory distress syndrome: the Berlin classification, which uses the relationship between the partial pressure of oxygen and the fraction of inspired oxygen, and the classification of the Pediatric Acute Lung Injury Consensus Conference, which uses the oxygenation index.
METHODS: This was a prospective study of patients aged 0 - 18 years with a diagnosis of acute respiratory distress syndrome who were invasively mechanically ventilated and provided one to three arterial blood gas samples, totaling 140 valid measurements. These measures were evaluated for correlation using the Spearman test and agreement using the kappa coefficient between the two classifications, initially using the general population of the study and then subdividing it into patients with and without bronchospasm and those with and without the use of neuromuscular blockers. The effect of these two factors (bronchospasm and neuromuscular blocking agent) separately and together on both classifications was also assessed using two-way analysis of variance.
RESULTS: In the general population, who were 54 patients aged 0 - 18 years a strong negative correlation was found by Spearman\'s test (ρ -0.91; p < 0.001), and strong agreement was found by the kappa coefficient (0.62; p < 0.001) in the comparison between Berlin and Pediatric Acute Lung Injury Consensus Conference. In the populations with and without bronchospasm and who did and did not use neuromuscular blockers, the correlation coefficients were similar to those of the general population, though among patients not using neuromuscular blockers, there was greater agreement between the classifications than for patients using neuromuscular blockers (kappa 0.67 versus 0.56, p < 0.001 for both). Neuromuscular blockers had a significant effect on the relationship between the partial pressure of oxygen and the fraction of inspired oxygen (analysis of variance; F: 12.9; p < 0.001) and the oxygenation index (analysis of variance; F: 8.3; p = 0.004).
CONCLUSIONS: There was a strong correlation and agreement between the two classifications in the general population and in the subgroups studied. Use of neuromuscular blockers had a significant effect on the severity of acute respiratory distress syndrome.

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A significant proportion of septic patients with acute lung injury (ALI) are recognized late due to the absence of an efficient diagnostic test, leading to the postponed treatments and consequently higher mortality. Identifying diagnostic biomarkers may improve screening to identify septic patients at high risk of ALI earlier and provide the potential effective therapeutic drugs. Machine learning represents a powerful approach for making sense of complex gene expression data to find robust ALI diagnostic biomarkers.
The datasets were obtained from GEO and ArrayExpress databases. Following quality control and normalization, the datasets (GSE66890, GSE10474 and GSE32707) were merged as the training set, and four machine learning feature selection methods (Elastic net, SVM, random forest and XGBoost) were applied to construct the diagnostic model. The other datasets were considered as the validation sets. To further evaluate the performance and predictive value of diagnostic model, nomogram, Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) were constructed. Finally, the potential small molecular compounds interacting with selected features were explored from the CTD database.
The results of GSEA showed that immune response and metabolism might play an important role in the pathogenesis of sepsis-induced ALI. Then, 52 genes were identified as putative biomarkers by consensus feature selection from all four methods. Among them, 5 genes (ARHGDIB, ALDH1A1, TACR3, TREM1 and PI3) were selected by all methods and used to predict ALI diagnosis with high accuracy. The external datasets (E-MTAB-5273 and E-MTAB-5274) demonstrated that the diagnostic model had great accuracy with AUC value of 0.725 and 0.833, respectively. In addition, the nomogram, DCA and CIC showed that the diagnostic model had great performance and predictive value. Finally, the small molecular compounds (Curcumin, Tretinoin, Acetaminophen, Estradiol and Dexamethasone) were screened as the potential therapeutic agents for sepsis-induced ALI.
This consensus of multiple machine learning algorithms identified 5 genes that were able to distinguish ALI from septic patients. The diagnostic model could identify septic patients at high risk of ALI, and provide potential therapeutic targets for sepsis-induced ALI.

Diagnostic guidelines for pediatric ARDS (PARDS) were developed at the 2015 Pediatric Acute Lung Injury Consensus Conference (PALICC). Although this was an improvement in creating pediatric-specific diagnostic criteria, there remains potential for variability in identification of PARDS.
What is the interrater reliability of the 2015 PALICC criteria for diagnosing moderate to severe PARDS? What clinical criteria and patient factors are associated with diagnostic disagreements?
Patients with acute hypoxic respiratory failure admitted from 2016 to 2021 who received invasive mechanical ventilation were retrospectively reviewed by two pediatric ICU physicians. Reviewers evaluated whether the patient met the 2015 PALICC definition of moderate to severe PARDS and rated their diagnostic confidence. Interrater reliability was measured using Gwet\'s agreement coefficient.
Thirty-seven of 191 encounters had a diagnostic disagreement. Interrater reliability was substantial (Gwet\'s agreement coefficient, 0.74; 95% CI, 0.65-0.83). Disagreements were caused by different interpretations of chest radiographs (56.8%), ambiguity in origin of pulmonary edema (37.8%), or lack of clarity if patient\'s current condition was significantly different from baseline (27.0%). Disagreement was more likely in patients who were chronically ventilated (OR, 4.66; 95% CI, 2.16-10.08; P < .001), had a primary cardiac admission diagnosis (OR, 3.36; 95% CI, 1.18-9.53; P = .02), or underwent cardiothoracic surgery during the admission (OR, 4.90; 95% CI, 1.60-15.00; P = .005). Reviewers were at least moderately confident in their decision 73% of the time; however, they were less likely to be confident if the patient had cardiac disease or chronic respiratory failure.
The interrater reliability of the 2015 PALICC criteria for diagnosing moderate to severe PARDS in this cohort was substantial, with diagnostic disagreements commonly caused by differences in chest radiograph interpretations. Patients with cardiac disease or chronic respiratory failure were more vulnerable to diagnostic disagreements. More guidance is needed on interpreting chest radiographs and diagnosing PARDS in these subgroups.

Diagnosis of pediatric acute respiratory distress syndrome (PARDS) in resource-limited settings (RLS) is challenging and remains poorly described. We conducted a review of the literature to optimize recognition of PARDS in RLS and to provide recommendations/statements for clinical practice and future research in these settings as part of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2).
MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).
We included studies related to precipitating factors for PARDS, mechanical ventilation (MV), pulmonary and nonpulmonary ancillary treatments, and long-term outcomes in children who survive PARDS in RLS.
Title/abstract review, full-text review, and data extraction using a standardized data collection form.
The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Seventy-seven studies were identified for full-text extraction. We were unable to identify any literature on which to base recommendations. We gained consensus on six clinical statements (good practice, definition, and policy) and five research statements. Clinicians should be aware of diseases and comorbidities, uncommon in most high-income settings, that predispose to the development of PARDS in RLS. Because of difficulties in recognizing PARDS and to avoid underdiagnosis, the PALICC-2 possible PARDS definition allows exclusion of imaging criteria when all other criteria are met, including noninvasive metrics of hypoxemia. The availability of MV support, regular MV training and education, as well as accessibility and costs of pulmonary and nonpulmonary ancillary therapies are other concerns related to management of PARDS in RLS. Data on long-term outcomes and feasibility of follow-up in PARDS survivors from RLS are also lacking.
To date, PARDS remains poorly described in RLS. Clinicians working in these settings should be aware of common precipitating factors for PARDS in their patients. Future studies utilizing the PALICC-2 definitions are urgently needed to describe the epidemiology, management, and outcomes of PARDS in RLS.

To develop evidence-based recommendations for the Second Pediatric Acute Lung Injury Consensus Conference (PALICC) regarding the effectiveness of noninvasive respiratory support for pediatric acute respiratory distress syndrome (PARDS). These include consideration of the timing and duration of noninvasive ventilation (NIV) and high-flow nasal cannula (HFNC), whether effectiveness varies by disease severity or by characteristics of treatment delivery, and best practices for the use of NIV.
MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).
Searches included all studies involving the use of NIV or HFNC in children with PARDS or hypoxemic respiratory failure.
Title/abstract review, full-text review, and data extraction using a standardized data extraction form.
The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Out of 6,336 studies, we identified 187 for full-text review. Four clinical recommendations were generated, related to indications, timing and duration of NIV in patients with PARDS, predictors of NIV failure and need for intubation (signs and symptoms of worsening disease including pulse oximetry saturation/Fio2 ratio), and use of NIV in resource-limited settings. Six good practice statements were generated related to how and where to deliver NIV, the importance of trained experienced staff and monitoring, types of NIV interfaces, the use of sedation, and the potential complications of this therapy. One research statement was generated related to indications of HFNC in patients with PARDS.
NIV is a widely used modality for the treatment of respiratory failure in children and may be beneficial in a subset of patients with PARDS. However, there needs to be close monitoring for worsening disease and NIV failure.

To systematically review and assimilate literature on children receiving extracorporeal membrane oxygenation (ECMO) support in pediatric acute respiratory distress syndrome (PARDS) with the goal of developing an update to the Pediatric Acute Lung Injury Consensus Conference recommendations and statements about clinical practice and research.
Electronic searches of MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).
The search used a medical subject heading terms and text words to capture studies of ECMO in PARDS or acute respiratory failure. Studies using animal models and case reports were excluded from our review.
Title/abstract review, full-text review, and data extraction using a standardized data collection form.
The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. There were 18 studies identified for full-text extraction. When pediatric data was lacking, adult and neonatal data from randomized clinical trials and observational studies were considered. Six clinical recommendations were generated related to ECMO indications, initiation, and management in PARDS. There were three good practice statements generated related to ECMO indications, initiation, and follow-up in PARDS. Two policy statements were generated involving the impact of ECMO team organization and training in PARDS. Last, there was one research statement.
Based on a systematic literature review, we propose clinical management, good practice and policy statements within the domains of ECMO indications, initiation, team organization, team training, management, and follow-up as they relate to PARDS.

Monitoring is essential to assess changes in the lung condition, to identify heart-lung interactions, and to personalize and improve respiratory support and adjuvant therapies in pediatric acute respiratory distress syndrome (PARDS). The objective of this article is to report the rationale of the revised recommendations/statements on monitoring from the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2).
MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).
We included studies focused on respiratory or cardiovascular monitoring of children less than 18 years old with a diagnosis of PARDS. We excluded studies focused on neonates.
Title/abstract review, full-text review, and data extraction using a standardized data collection form.
The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. We identified 342 studies for full-text review. Seventeen good practice statements were generated related to respiratory and cardiovascular monitoring. Four research statements were generated related to respiratory mechanics and imaging monitoring, hemodynamics monitoring, and extubation readiness monitoring.
PALICC-2 monitoring good practice and research statements were developed to improve the care of patients with PARDS and were based on new knowledge generated in recent years in patients with PARDS, specifically in topics of general monitoring, respiratory system mechanics, gas exchange, weaning considerations, lung imaging, and hemodynamic monitoring.

We conducted an updated review of the literature on pulmonary-specific ancillary therapies for pediatric acute respiratory distress syndrome (PARDS) to provide an update to the Pediatric Acute Lung Injury Consensus Conference recommendations and statements about clinical practice and research.
MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).
Searches were limited to children, PARDS or hypoxic respiratory failure and overlap with pulmonary-specific ancillary therapies.
Title/abstract review, full-text review, and data extraction using a standardized data collection form.
The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Twenty-six studies were identified for full-text extraction. Four clinical recommendations were generated, related to use of inhaled nitric oxide, surfactant, prone positioning, and corticosteroids. Two good practice statements were generated on the use of routine endotracheal suctioning and installation of isotonic saline prior to endotracheal suctioning. Three research statements were generated related to: the use of open versus closed suctioning, specific methods of airway clearance, and various other ancillary therapies.
The evidence to support or refute any of the specific ancillary therapies in children with PARDS remains low. Further investigation, including a focus on specific subpopulations, is needed to better understand the role, if any, of these various ancillary therapies in PARDS.