Pediatric Acute Respiratory Distress Syndrome Research Articles

PP180 Topic: AS16–Medical, Nursing and AHP Workforce & Education: Staff Education and Development/Equity, Diversity, Inclusion/Other: EVALUATION OF RESIDENTS’ MECHANICAL VENTILATION MANAGEMENT BEHAVIORS IN A SIMULATED ONLINE PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME CASE SCENARIO

PP180 Topic: AS16–Medical, Nursing and AHP Workforce & Education: Staff Education and Development/Equity, Diversity, Inclusion/Other: EVALUATION OF RESIDENTS’ MECHANICAL VENTILATION MANAGEMENT BEHAVIORS IN A SIMULATED ONLINE PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME CASE SCENARIO

RNA Sequencing Analysis of Monocytes Exposed to Airway Fluid From Children With Pediatric Acute Respiratory Distress Syndrome.

Monocytes are plastic cells that assume different polarization states that can either promote inflammation or tissue repair and inflammation resolution. Polarized monocytes are partially defined by their transcriptional profiles that are influenced by environmental stimuli. The airway monocyte response in pediatric acute respiratory distress syndrome (PARDS) is undefined. To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor monocytes exposed to the airway fluid of intubated children with and at-risk for PARDS. To determine differences in gene expression at two time points using the donor monocyte assay exposed to airway fluid from intubated children with PARDS obtained 48-96 hours following initial tracheal aspirate sampling. In vitro pilot study carried out using airway fluid supernatant. Academic 40-bed PICU. Fifty-seven children: 44 children with PARDS and 13 children at-risk for PARDS. None. We performed bulk RNA sequencing using a transcriptomic reporter assay of monocytes exposed to airway fluid from intubated children to discover gene networks differentiating PARDS from at-risk for PARDS and those differentiating mild/moderate from severe PARDS. We also report differences in gene expression in children with PARDS 48-96 hours following initial tracheal aspirate sampling. We found that interleukin (IL)-10, IL-4, and IL-13, cytokine/chemokine signaling, and the senescence-associated secretory phenotype are upregulated in monocytes exposed to airway fluid from intubated children with PARDS compared with those at-risk for PARDS. Signaling by NOTCH, histone deacetylation/acetylation, DNA methylation, chromatin modifications (B-WICH complex), and RNA polymerase I transcription and its associated regulatory apparatus were upregulated in children with PARDS 48-96 hours following initial tracheal aspirate sampling. We identified gene networks important to the PARDS airway immune response using bulk RNA sequencing from a monocyte reporter assay that exposed monocytes to airway fluid from intubated children with and at-risk for PARDS. Mechanistic investigations are needed to validate our findings.

Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. NCT03266016; August 23, 2017.

CIRCULATING HEPARAN SULFATE PROFILES IN PEDIATRIC ACUTE RESPIRATORY DISTRESS SYNDROME.

Introduction: Sepsis-induced degradation of endothelial glycocalyx heparan sulfate (HS) contributes to the pulmonary microvascular endothelial injury characteristic of acute respiratory distress syndrome (ARDS) pathogenesis. Our objectives were to (1) examine relationships between plasma indices of HS degradation and protein biomarkers of endothelial injury and (2) identify patient subgroups characterized by distinct profiles of HS degradation in children with ARDS. Methods: We analyzed prospectively collected plasma (2018-2020) from a cohort of invasively mechanically ventilated children (aged >1 month to <18 years) with ARDS. Mass spectrometry characterized and quantified patterns of HS disaccharide sulfation. Protein biomarkers reflective of endothelial injury (e.g., angiopoietin-2, vascular cell adhesion molecule-1, soluble thrombomodulin) were measured with a multiplex immunoassay. Pearson correlation coefficients were used to construct a biomarker correlation network. Centrality metrics detected influential biomarkers (i.e., network hubs). K-means clustering identified unique patient subgroups based on HS disaccharide profiles. Results: We evaluated 36 patients with pediatric ARDS. HS disaccharide sulfation patterns, 6S, NS, and NS2S, positively correlated with all biomarkers of endothelial injury (all P < 0.05) and were classified as network hubs. We identified three patient subgroups, with cluster 3 (n = 5) demonstrating elevated levels of 6S and N-sulfated HS disaccharides. In cluster 3, 60% of children were female and nonpulmonary sepsis accounted for 60% of cases. Relative to cluster 1 (n = 12), cluster 3 was associated with higher oxygen saturation index (P = 0.029) and fewer 28-day ventilator-free days (P = 0.016). Conclusions: Circulating highly sulfated HS fragments may represent emerging mechanistic biomarkers of endothelial injury and disease severity in pediatric ARDS.

Impact of the transpulmonary pressure on right ventricle impairment incidence during acute respiratory distress syndrome: a pilot study in adults and children

BackgroundRight ventricle impairment (RVI) is common during acute respiratory distress syndrome (ARDS) in adults and children, possibly mediated by the level of transpulmonary pressure (PL). We sought to investigate the impact of the level of PL on ARDS-associated right ventricle impairment (RVI).MethodsAdults and children (> 72 h of life) were included in this two centers prospective study if they were ventilated for a new-onset ARDS or pediatric ARDS, without spontaneous breathing and contra-indication to esophageal catheter. Serial measures of static lung, chest wall, and respiratory mechanics were coupled to critical care echocardiography (CCE) for 3 days. Mixed-effect logistic regression models tested the impact of lung stress (ΔPL) along with age, lung injury severity, and carbon dioxide partial pressure, on RVI using two definitions: acute cor pulmonale (ACP), and RV dysfunction (RVD). ACP was defined as a dilated RV with septal dyskinesia; RVD was defined as a composite criterion using tricuspid annular plane systolic excursion, S wave velocity, and fractional area change.Results46 patients were included (16 children, 30 adults) with 106 CCE (median of 2 CCE/patient). At day one, 19% of adults and 4/7 children > 1 year exhibited ACP, while 59% of adults and 44% of children exhibited RVD. In the entire population, ACP was present on 17/75 (23%) CCE. ACP was associated with an increased lung stress (mean ΔPL of 16.2 ± 6.6 cmH2O in ACP vs 11.3 ± 3.6 cmH2O, adjusted OR of 1.33, CI95% [1.11–1.59], p = 0.002) and being a child. RVD was present in 59/102 (58%) CCE and associated with lung stress. In children > 1 year, PEEP was significantly lower in case of ACP (9.3 [8.6; 10.0] cmH2O in ACP vs 15.0 [11.9; 16.3] cmH2O, p = 0.03).ConclusionLung stress was associated with RVI in adults and children with ARDS, children being particularly susceptible to RVI.Trial registration Clinical trials identifier: NCT0418467.

Transpulmonary Pressure-Guided Mechanical Ventilation in Severe Acute Respiratory Distress Syndrome in PICU: Single-Center Retrospective Study in North India, 2018–2021

Objectives: In this study, we have reviewed the association between esophageal pressure-guided positive end-expiratory pressure (PEEP) setting and oxygenation and lung mechanics with a conventional mechanical ventilation (MV) strategy in patient with moderate to severe pediatric acute respiratory distress syndrome (PARDS). Design: Retrospective cohort, 2018–2021. Setting: Tertiary PICU. Patients: Moderate to severe PARDS patients who required MV with PEEP of greater than or equal to 8 cm H2O. Interventions: Esophageal pressure (i.e., transpulmonary pressure [PTP]) guided MV vs. not. Measurements and Main Results: We identified 26 PARDS cases who were divided into those who had been managed with PTP-guided MV (PTP group) and those managed with conventional ventilation strategy (non-PTP). Oxygenation and lung mechanics were compared between groups at baseline (0 hr) and 24, 48, and 72 hours of MV. There were 13 patients in each group in the first 24 hours. At 48 and 72 hours, there were 11 in PTP group and 12 in non-PTP group. On comparing these groups, first, use of PTP monitoring was associated with higher median (interquartile range) mean airway pressure at 24 hours (18 hr [18–20 hr] vs. 15 hr [13–18 hr]; p = 0.01) and 48 hours (19 hr [17–19 hr] vs. 15 hr [13–17 hr]; p = 0.01). Second, use of PTP was associated with higher PEEP at 24, 48, and 72 hours (all p &lt; 0.05). Third, use of PTP was associated with lower Fio 2 and greater Pao 2 to Fio 2 ratio at 72 hours. Last, there were 18 of 26 survivors, and we failed to identify an association between use of PTP monitoring and survival. Conclusions: In this cohort of moderate to severe PARDS cases undergoing MV with PEEP greater than or equal to 8 cm H2O, we have identified some favorable associations of oxygenation status when PTP-guided MV was used vs. not. Larger studies are required.

The impact of PEEP on mechanical power and driving pressure in children with pediatric acute respiratory distress syndrome.

Positive end-expiratory pressure (PEEP) is widely used to improve oxygenation and avoid alveolar collapse in mechanically ventilated patients with pediatric acute respiratory distress syndrome (PARDS). However, its improper use can be harmful, impacting variables associated with ventilation-induced lung injury, such as mechanical power (MP) and driving pressure (∆P). Our main objective was to assess the impact of increasing PEEP on MP and ∆P in children with PARDS. Mechanically ventilated children on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8, and again to 5 cm H2O. After 10 min at each PEEP level, ventilatory data were collected and then variables of interest were determined. Respiratory system mechanics were measured using the least squares fitting method. Thirty-one patients were included, with median age and weight of 6 months and 6.3 kg. Most subjects were admitted for acute viral bronchiolitis (45%) or community-acquired pneumonia (32%) and were diagnosed with mild (45%) or moderate (42%) PARDS. There was a significant increase in MP and ∆P at PEEP levels of 10 and 12 cm H2O. When PEEP was increased from 5 to 12 cm H2O, there was a relative increase in MP of 60.7% (IQR 49.3-82.9) and in ΔP of 33.3% (IQR 17.8-65.8). A positive correlation was observed between MP and ΔP (ρ = 0.59). Children with mild or moderate PARDS may experience a significant increase in MP and ∆P with increased PEEP. Therefore, respiratory system mechanics and lung recruitability must be carefully evaluated during PEEP titration.

Respiratory Syncytial Virus Infections in Pediatric Intensive Care: Association of Sociodemographic Data and Clinical Outcomes with Viral and Bacterial Co-infections.

The aim of the study was to evaluate respiratory syncytial virus (RSV) infections in cases followed in the pediatric intensive care unit (PICU). The study was designed as a prospective cohort in 6 PICUs. There were 3 groups: only RSV (+), RSV (v+) who were positive for another viral agent(s) in addition to RSV, and RSV (b+) who were positive for a bacterial agent(s) in addition to RSV. A total of 119 cases were included in the study, 67 (56.3%) of whom were male. The RSV (+) group had a lower pH compared to the other groups and a higher rate of acute bronc hiolitis/bronchitis diagnoses compared to the RSV (v+) group. The RSV (v+) group had higher bicarbonate levels, higher creatinine levels, longer hospital stays, and higher Pediatric Risk of Mortality-3 scores (PRISM-3) compared to the RSV (+) group. Cases with RSV (b+) were younger and also had lower body weight compared to the other groups. Furthermore, the RSV (b+) group had higher C-reactive protein and Procalcitonin (PCT) levels and higher rates of High Flow Nasal Cannula-Oxygen Therapy (HFNC-OT) use. Multiple linear regression analysis revealed that PRISM-3 score, PCT levels, Pediatric Acute Respiratory Distress Syndrome diagnoses, inhaled steroid use, chronic illness status, and heart rate on admission were associated with the length of stay in the PICU. High flow nasal cannula-oxygen therapy continues to be the most frequently preferred respiratory support method in RSV infections. Viral infections accompanying RSV can increase the severity of the disease.

Mechanical Power in Decelerating Flow versus Square Flow Ventilation in Pediatric Acute Respiratory Distress Syndrome.

Mechanical power is a summary variable quantifying the risk of ventilator-induced lung injury. The original mechanical power equation was developed using square flow ventilation. However, most children are ventilated using decelerating flow. It is unclear whether mechanical power differs according to mode of flow delivery. This study compared mechanical power in children with acute respiratory distress syndrome who received both square and decelerating flow ventilation. This was a secondary analysis of a prospectively enrolled cohort of pediatric acute respiratory distress syndrome. Patients were ventilated on decelerating flow and then placed in square flow and allowed to stabilize. Ventilator metrics from both modes were collected within 24 h of acute respiratory distress syndrome onset. Paired t tests were used to compare differences in mechanical power between the modes. This study enrolled 185 subjects with a median oxygenation index of 9.5 (interquartile range, 7 to 13) and median age of 8.3 yr (interquartile range, 1.8 to 14). Mechanical power was lower in square flow mode (mean, 0.46 J · min-1 · kg-1; SD, 0.25; 95% CI, 0.42 to 0.50) than in decelerating flow mode (mean, 0.49 J · min-1 · kg-1; SD, 0.28; 95% CI, 0.45 to 0.53) with a mean difference of 0.03 J · min-1 · kg-1 (SD, 0.08; 95% CI, 0.014 to 0.038; P < 0.001). This result remained statistically significant when stratified by age of less than 2 yr in square flow compared to decelerating flow and also when stratified by age of 2 yr or greater in square flow compared to decelerating flow. The elastic contribution in square flow was 70%, and the resistive contribution was 30%. Mechanical power was marginally lower in square flow than in decelerating flow, although the clinical significance of this is unclear. Upward of 30% of mechanical power may go toward overcoming resistance, regardless of age. This is nearly three-fold greater resistance compared to what has been reported in adults.

MiR-629-5p May serve as a biomarker for pediatric acute respiratory distress syndrome and can regulate the inflammatory response

ObjectiveCirculating microRNAs (miRNAs) are associated with pediatric acute respiratory distress syndromes (PARDS). This study analyzed the clinical significance and potential mechanism of microRNA (miR)-629-5p in PARDS. Methods82 children with PARDS and 82 controls were enrolled. Serum levels of miR-629-5p were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and its diagnostic significance with respect to for PARDS in children was assessed by the receiver operating characteristic (ROC). Kaplan-Meier curve and multivariate Cox regression were utilized to examine the prognostic significance of miR-629-5p. An in vitro cell model was established using lipopolysaccharide (LPS)-induced alveolar epithelial cells A549. The cell proliferation, apoptosis, and inflammatory factors were assessed using cell counting kit-8 (CCK-8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA). miR-629-5p target genes were identified in the database and validated using the dual-luciferase report assay. ResultsSerum miR-629-5p levels were significantly higher in children with PARDS than in controls (P < 0.05). miR-629-5p exhibited 86.6% sensitivity and 91.5% specificity in distinguishing children with PARDS. miR-629-5p was an independent risk factor for mortality, and high levels of miR-629-5p have a poor prognosis. LPS promoted apoptosis and overproduction of inflammatory factors in A549 and upregulated miR-629-5p expression (P < 0.05); however, they were partially reversed by the weakened miR-629-5p (P < 0.05). Syndecan-4 (SDC4) is a target of miR-629-5p. The inhibition of SDC4 induced by LPS can be alleviated through the reduction of miR-629-5p. ConclusionmiR-629-5p serves as a diagnostic biomarker for children with PARDS and it is associated with poor prognosis. Diminished miR-629-5p may alleviate PARDS by targeting SDC4 to suppress apoptosis and inflammation of alveolar epithelial cells.

The Impact of Increased PEEP on Hemodynamics, Respiratory Mechanics, and Oxygenation in Pediatric ARDS.

PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS. Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected. A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8-12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O). Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability.

Prognostic factors of extracorporeal membrane oxygenation in the treatment of severe pediatric acute respiratory distress syndrome

Objective: To explore the factors affecting the prognosis of severe pediatric acute respiratory distress syndrome (ARDS) after receiving extracorporeal membrane oxygenation (ECMO) support. Methods: It was a multicenter prospective observational study. A total of 95 children with severe ARDS who were treated with ECMO salvage therapy from January 2018 to December 2022 in 9 pediatric ECMO centers in China were enrolled in the study. The general data, disease severity, organ function, comprehensive treatment and prognosis were recorded, and they were divided into survival group and death group according to the outcome at discharge. T test, chi-square test, multivariate Logistic regression and mixed linear model were used to analyze the relationship among baseline before ECMO treatment, some important indicators (pediatric critical scores, platelet count, albumin, fibrinogen, etc) during ECMO treatment and prognosis. Results: Among the 95 children with severe ARDS who received ECMO, 55 (58%) were males and 40 (42%) were females, aged 36.9 (0.5, 72.0) months. Twelve children (13%) were immunodeficient. Sixty-eight (72%) children were treated with venous artery (VA) mode and 27 (28%) with venous vein (VV) mode. The discharge survival rates of overall, VA, and VV mode children were 51% (48/95), 47% (32/68), and 59% (16/27), respectively. The number of immunodeficient children in the death group was higher, and there were lower pediatric critical scores, platelet count, albumin, fibrinogen and arterial oxygen partial pressure/fraction of inspired oxygen (PaO2/FiO2), higher ventilator driving pressure (ΔP), oxygenaion index (OI), and longer ARDS duration before ECMO (all P<0.05). There were no statistically significant differences in other indicators, including age, gender, weight, and ECMO mode among different prognostic groups (all P>0.05). High ΔP, high OI, low P/F, and low albumin were high-risk factors affecting prognosis(all P<0.05). After further grouping, it was found that ΔP≥25 cmH2O (1 cmH2O=0.098 kPa), P/F≤67 mmHg (1 mmHg=0.133 kPa) and OI≥35 were the thresholds for predicting poor prognosis (P<0.05). From 24 h after ECMO, there were significant differences in ΔP, P/F and OI between the dead group and the survival group (all P<0.05), and the differences gradually increased with the ECMO process. The platelet level was significant from 7 days after ECMO (P<0.05) and gradually expanded. Blood lactate levels showed a significant difference between the 2 groups on before and after ECMO (P<0.05) and gradually increased from 24 h after ECMO. Conclusions: The risk factors affecting the prognosis of severe ARDS in ECMO include high ΔP, high OI, low P/F and low albumin purification therapy before ECMO. The gradual decrease of ΔP, OI and increase of P/F from 24 h of ECMO predicted a good prognosis, while the gradual increase of lactate after ECMO application showed a poor prognosis.

The Association between Dynamic Pressure Gradient and Mortality in Patients with Acute Respiratory Distress Syndrome in a Pediatric Intensive Care Unit: A Single-Center Retrospective Cohort

Abstract Background: Lung-protective ventilation strategies, one of which is to limit peak inspiratory pressure (PIP), are recommended in the management of acute respiratory distress syndrome (ARDS). The purpose of this study was to determine whether dynamic pressure gradient, defined as the difference between PIP and positive end-expiratory pressure (PEEP), is associated with pediatric ARDS mortality in the pediatric intensive care unit (PICU). Materials and Methods: This was a retrospective, single-center cohort study with consecutive sampling. Children aged 1 month to 18 years with ARDS who were admitted to PICU and used invasive mechanical ventilator between January and December 2023 were included. Patient’s demographic data, pediatric logistic organ dysfunction 2 (PELOD-2) score, oxygenation index (OI), oxygen saturation index (OSI), PEEP, and dynamic pressure gradient were collected from the patient’s medical record. The outcome is mortality, which is measured upon discharge. Results: The subjects’ median age was 6 months, predominantly male (64.06%). The etiology of ARDS was pneumonia (90.63%) and sepsis (9.37%). Bivariate analysis showed that dynamic pressure gradient (OR = 4.77, 95% CI=1.47–15.5, P = 0.003), PEEP (OR = 3.21, 95% CI = 1.07–9.52, P = 0.033), and PELOD-2 score at 24–72 h (OR = 3.68, 95% CI = 1.146–11.83, P = 0.024) had a significant association with mortality of ARDS patients at PICU. The results of multivariate analysis showed that dynamic pressure gradient had a significant relationship with the mortality of ARDS patients at PICU (OR = 5.22, 95% CI = 1.47–18.56, P = 0.015). Conclusion: Dynamic pressure gradient was associated with mortality in pediatric patients with ARDS who were treated in PICU.

Infant feeding and criticality in children.

Data support the protective effects of human breast milk (HBM) feeding in acute illness but little is known about the impact of HBM feeding on the criticality of infants. To explore the relationship between early HBM feeding and severity of illness and recovery in critically ill children requiring intubation and mechanical ventilation for acute respiratory failure (ARF). Prospective cohort study of mothers of patients aged 1-36 months who participated in the acute and follow-up phases of the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial. Participants completed a survey describing HBM dose fed during their infant's first month of life. Of 138 patients, 70 (51%) received exclusive HBM feedings (90%-100% total feeds) and 68 (49%) did not. We found no group differences in severity of illness on paediatric intensive care unit (PICU) admission or severity of paediatric acute respiratory distress syndrome (PARDS) within the first 24-48 h of intubation/mechanical ventilation (Pediatric Risk of Mortality [PRISM] III-12 score median: 5 vs. 5, p = .88; moderate/severe PARDS: 53% vs. 54%, p = .63). While median time to recovery from ARF was reduced by 1 day in patients who received exclusive HBM feedings, the difference between groups was not statistically significant (median 1.5 vs. 2.6 days, hazard ratio 1.40 [95% confidence interval, 0.99-1.97], p = .06). Human breast milk dose was not associated with severity of illness on PICU admission in children requiring mechanical ventilation for ARF. Data support the protective effects of HBM during acute illness and data from this study support a clinically important reduction in time to recovery of ARF. Paediatric nurses should continue to champion HBM feeding to advance improvements in infant health.

New Right Ventricular Dysfunction in Pediatric Acute Respiratory Distress Syndrome on Venovenous Extracorporeal Membrane Oxygenation.

The development of new right ventricular (RV) dysfunction after cannulation to venovenous (VV) extracorporeal membrane oxygenation (ECMO) and its association with worse outcomes is increasingly recognized in adult patients, however, no studies have evaluated this phenomenon in pediatric patients. We report results of a single-center retrospective cohort study at a large academic children's hospital. New RV systolic dysfunction was present in 48% (12/25) of pediatric patients on VV ECMO for acute respiratory distress syndrome (ARDS). There was no statistically significant difference in survival, duration of mechanical ventilation, or hospital length of stay between those with and without RV dysfunction. Over half (5/9, 56%) of survivors with RV dysfunction on ECMO had RV dilation or RV hypertrophy on post-ECMO echocardiograms, and in two patients the RV dysfunction persisted for months following decannulation. Cardiac catheterization and autopsy reports suggested that echocardiographic assessment of RV systolic function alone may not be sufficient to diagnose clinically relevant RV injury. This is the first study to report the prevalence of RV dysfunction on VV ECMO for pediatric ARDS. Future multicenter collaboration is needed to create a clinically relevant definition of pediatric "RV injury" and to further evaluate risk factors and outcomes of RV dysfunction.

Pediatric Acute Respiratory Distress Syndrome Severity and Health-Related Quality of Life Outcomes: Single-Center Retrospective Cohort, 2011-2017.

To determine factors associated with health-related quality of life (HRQL) decline among pediatric acute respiratory distress syndrome (PARDS) survivors. Retrospective cohort study. Academic children's hospital. Three hundred fifteen children 1 month to 18 years old with an unplanned PICU admission from December 2011 to February 2017 enrolled in the hospital's Outcomes Assessment Program. None. Pre-admission baseline and median 6-week post-discharge HRQL were assessed using the Pediatric Quality of Life Inventory or the Functional Status II-R. Patients meeting retrospectively applied Second Pediatric Acute Lung Injury Consensus Conference criteria for PARDS were identified, and PARDS severity was classified using binary (mild/moderate, severe) and trichotomous (mild, moderate, severe) categorization for noninvasive ventilation and invasive mechanical ventilation (IMV). PARDS occurred in 41 of 315 children (13.0%). Clinically important HRQL decline (≥ 4.5 points) occurred in 17 of 41 patients (41.5%) with PARDS and 64 of 274 without PARDS (23.4%). On multivariable generalized linear regression adjusted for age, baseline Pediatric Overall Performance Category, maximum nonrespiratory Pediatric Logistic Organ Dysfunction score, diagnosis, length of stay, and time to follow-up, PARDS was associated with HRQL decline (adjusted relative risk [aRR], 1.70; 95% CI, 1.03-2.77). Four-hour and maximum PARDS severity were the only factors associated with HRQL decline. HRQL decline occurred in five of 18 patients with mild PARDS at 4 hours, five of 13 with moderate PARDS (aRR 2.35 vs. no PARDS [95% CI, 1.01-5.50]), and seven of ten with severe PARDS (aRR 2.56 vs. no PARDS [95% CI, 1.45-4.53]). The area under the receiver operating characteristic curve for discrimination of HRQL decline for IMV patients was 0.79 (95% CI, 0.66-0.91) for binary and 0.80 (95% CI, 0.69-0.93) for trichotomous severity categorization. HRQL decline is common among children surviving PARDS, and risk of decline is associated with PARDS severity. HRQL decline from baseline may be an efficient and clinically meaningful endpoint to incorporate into PARDS clinical trials.

Potential risk factors of pediatric acute respiratory distress syndrome in sepsis

Background Sepsis in children is characterized by a dysregulated host response to infection and life-threatening organ dysfunction. Pediatric acute respiratory distress syndrome (PARDS) is a severe complication of sepsis. Several known risk factors of PARDS are immunodeficiency, obesity, source of infection, and genetic factors. Objective To describe the potential risk factors of PARDS in septic children at Haji Adam Malik General Hospital, Medan, North Sumatera. Methods This descriptive study using eligible medical record data from sepsis patients aged 1 month – 18 years was conducted at Haji Adam Malik General Hospital in 2020–2022. A total sampling method was used for subject selection. Patients’ demographic and clinical characteristics, mechanical ventilation modes and parameters, laboratory results, and outcomes were collected from medical records. Patients were classified as having sepsis with PARDS if Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria of ARDS was met. Results Of 112 pediatric sepsis patients, 33.9% developed PARDS. The mortality rates for PARDS was 73.7%. Of the patients with PARDS, 57.9% had immunodeficiency, 60.5% patients had an intrapulmonary infection, 39.5% had an extrapulmonary infection, and 23.7% of patients had a suspected genetic disorder. In addition, 39.5% had good nutritional status, followed by 21.1% with obese. Conclusion The majority of patients with PARDS have intrapulmonary infection and immunodeficiency. Some of patients with PARDS have suspected genetic disorders and well nourished.

Time to split: biomarker trajectories in pediatric acute respiratory distress syndrome hint at underlying disease.

Pediatric acute respiratory distress syndrome (ARDS) is severe, noncardiac hypoxemic respiratory failure that carries a substantial risk of death. Given the complexity of this clinically defined syndrome and the repeated failure of therapeutic trials, there has been an effort to identify subphenotypes of ARDS that may share targetable mechanisms of disease. In this issue of the JCI, Yehya and colleagues measured 19 plasma biomarkers in 279 children over the first seven days of ARDS. Increases in select tissue injury makers and inflammatory cytokines in peripheral blood were associated with multiple organ dysfunction syndrome and death, but not persistent ARDS. These findings argue that splitting patients by clinical and molecular phenotype may be more informative than lumping them under the umbrella diagnosis of ARDS. However, future studies are needed to determine whether these plasma factors represent targetable pathways in lung injury or are a consequence of systemic organ dysfunction.

Yes-associated Protein Mediates Acute Lung Injury in Adult but not Juvenile Mice

Objective: Adults with The Acute Respiratory Distress Syndrome (ARDS) have worse outcomes than children with Pediatric ARDS. This finding can be reproduced in animal models, suggesting a difference in Acute Lung Injury (ALI) mechanisms. Understanding these mechanistic differences could inform age-specific treatment. Hypothesis: Since Yes-associated protein (YAP) is important for lung development and reactive to mechanical stretch, we hypothesized that YAP is important for ALI mechanisms. Methods: To induce ALI, we intranasally instilled mice with Pseudomonas aeruginosa strain K (2.5 x 105 colony forming units (c.f.u.)) in juvenile (3-week-old) and adult (10-week-old) C57BL/6J mice. 24 h later, we collected bronchoalveolar lavage (BAL) fluid and measured protein, cell count, and c.f.u. To knockdown YAP expression, we injected siRNA 24 h before P. aeruginosa instillation. We removed the lungs and enriched for CD45+ and CD41+ fraction, and CD31+ fraction using Dynabeads sheep anti-rat IgG (Invitrogen). In separate experiments, lungs were separated into nuclear and cytosolic fractions for immunoblot analysis. For immunoprecipitation, the cytosolic fraction was added to beads coated with anti-YAP antibody (rabbit monoclonal). We washed the beads and eluted bound proteins, which were identified by label-free mass spectrometry. Data and results: While both juvenile and adult mice had significantly increased BAL cell counts and protein 24 h after P. aeruginosa instillation, adult mice had significantly greater cell counts and protein than juveniles. BAL c.f.u. were similar in both groups, suggesting equal instillation of P. aeruginosa. P. aeruginosa instillation increased whole lung YAP expression in both cytosolic and nuclear fractions in adult mice by &gt;3-fold, but YAP expression was not increased in P. aeruginosa-treated juvenile mice. YAP protein increases occurred in CD31+ fraction (endothelial cells), but no YAP was quantified in CD45+/CD41+ fraction (leukocytes and platelets). Vascular knockdown of YAP expression by ~75% in adult mice blocked P. aeruginosa-induced BAL cell count increases. Proteomics analysis revealed 62 proteins that had significantly altered YAP binding upon P. aeruginosa treatment (47 with increased YAP binding). The complement factors H and I had a log2-fold-change for YAP binding of 4.56 and 2.26, respectively, upon P. aeruginosa treatment. Conclusions: Adult mice exhibited YAP-dependent Acute Lung Injury; juveniles did not. YAP-dependent mechanisms of injury may be secondary to YAP binding to the complement inhibitory proteins H and I. More work is needed to establish the cell-specificity of YAP-complement factor binding and to determine the location of complement signaling. HL148403, Parker B Francis, and Columbia University Department of Pediatrics Children’s Health Innovation Nucleation Fund to RFH; Ernest E Just Summer Scholarship to AMD. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Master Protocol Template for Pediatric ARDS Studies.

Pediatric ARDS is associated with significant morbidity and mortality. High-quality data from clinical trials in children are limited due to numerous barriers to their design and execution. Here we describe the collaborative development of a master protocol as a tool to address some of these barriers and support the conduct of pediatric ARDS studies. Using PubMed, we performed a literature search of randomized controlled trials (RCTs) in pediatric ARDS to characterize the current state and evaluate potential benefit of harmonized master protocols. We used a multi-stakeholder, collaborative, and team science-oriented process to develop a master protocol template with links to common data elements (CDEs) for pediatric ARDS trials. We identified 11 RCTs that enrolled between 14-200 total subjects per trial. Interventions included mechanical ventilation, prone positioning, corticosteroids, and surfactant. Studies displayed significant heterogeneity in ARDS definition, design, inclusion and exclusion criteria, and reported outcomes. Mortality was reported in 91% of trials and ventilator-free days in 73%. The trial heterogeneity made pooled analysis unfeasible. These findings underscore the need for a method to facilitate combined analysis of future trials through standardization of trial elements. As a potential solution, we developed a master protocol, iteratively revised with input from a multidisciplinary panel of experts and organized into 3 categories: instructions and general information, templated language, and a series of text options of common pediatric ARDS trial scenarios. Finally, we linked master protocol sections to relevant CDEs previously defined for pediatric ARDS and captured in a series of electronic case report forms. The majority of pediatric ARDS trials identified were small and heterogeneous in study design and outcome reporting. Using a master protocol template for pediatric ARDS trials with CDEs would support combining and comparing pediatric ARDS trial findings and increase the knowledge base.