Daily Ards Research Analysis
Analyzed 9 papers and selected 3 impactful papers.
Summary
A harmonized bi-national ARDS cohort study links inflammatory phenotypes with mortality and differential sensitivity to lung-protective ventilation metrics, informing enrichment strategies for future trials. Large-scale neonatal registry data highlight stark global disparities in surfactant access, timing, and outcomes, while a retrospective cohort suggests measurable oxygenation gains with surfactant retreatment in very preterm infants.
Research Themes
- ARDS precision phenotyping and ventilatory risk
- Global equity in neonatal respiratory care
- Optimization of surfactant dosing and retreatment
Selected Articles
1. Effects of inflammatory phenotypes in acute respiratory distress syndrome on mortality and partitioning of lung and chest wall mechanics in patients in the USA and Canada: a retrospective cohort study.
In a harmonized cohort of 890 adults with moderate-to-severe ARDS monitored by esophageal manometry, 60-day mortality was 55% in the hyperinflammatory phenotype versus 29% in the hypoinflammatory phenotype. High respiratory system driving pressure and transpulmonary driving pressure had a stronger association with mortality in the hypoinflammatory phenotype, despite broadly similar lung mechanics across phenotypes.
Impact: This study bridges biological phenotypes with respiratory mechanics and ventilatory exposures, sharpening risk stratification and informing trial enrichment for ARDS precision medicine.
Clinical Implications: For ARDS (acute respiratory distress syndrome), hypoinflammatory patients may derive particular benefit from stringent control of driving and transpulmonary driving pressures; however, immediate phenotype-based ventilation changes are not yet supported. The findings support phenotype-enriched trial designs and vigilant prevention of extrapulmonary organ failure in hyperinflammatory ARDS.
Key Findings
- Among 890 ARDS patients, 60-day mortality was 55% (hyperinflammatory) vs 29% (hypoinflammatory).
- Higher respiratory system driving pressure and transpulmonary driving pressure were more strongly associated with mortality in the hypoinflammatory phenotype.
- Lung mechanics were broadly similar across phenotypes; excess mortality in hyperinflammatory ARDS was driven by extrapulmonary organ failure.
- Data harmonized across EPVent-2 trial sites and a tertiary-center cohort with esophageal manometry.
Methodological Strengths
- Harmonized multi-cohort dataset including randomized-trial monitoring and real-world cohort with esophageal manometry
- Phenotype-stratified multivariable Cox models assessing ventilatory metrics and mortality
Limitations
- Retrospective observational design limits causal inference
- Potential misclassification of phenotypes and residual confounding; generalizability limited to patients monitored with esophageal manometry
Future Directions: Prospective, phenotype-enriched trials testing ventilatory targets (e.g., driving pressure) and organ-support strategies; integration of biological markers with continuous respiratory mechanics monitoring.
BACKGROUND: Inflammatory phenotypes of acute respiratory distress syndrome (ARDS) predict outcomes and can respond differently to treatment strategies. We aimed to establish whether these phenotypes differ in respiratory mechanics and in response to lung-protective ventilation strategies. METHODS: In this retrospective cohort study, data from two cohorts were harmonised. Patients with moderate-to-severe ARDS with oesophageal manometry data from the EPVent-2 trial (14 hospitals across the USA and Canada) and a retrospective cohort at Beth Israel Deaconess Medical Center (Boston, MA, USA) were merged and lung mechanics were compared. Patients had to be aged 18 years or older, have moderate to severe ARDS, and be monitored with oesophageal manometry. To analyse the primary outcome of 60-day mortality after ARDS onset, we used multivariable Cox models for each inflammatory phenotype to study the associations between measures of lung-protective ventilation (driving pressure, transpulmonary driving pressure, and end-expiratory transpulmonary pressure) and 60-day mortality in all patients who had complete data for all variables. FINDINGS: Between Jan 1, 2008, and Jan 31, 2024, 5778 patients were assessed for eligibility (200 in the EPVent-2 cohort and 5578 in the BIDMC cohort). Of these patients, 890 were included in this study cohort (200 from the EPVent-2 trial and 690 from the retrospective cohort), of whom 424 (48%) had the hyperinflammatory phenotype and 466 (52%) had the hypoinflammatory phenotype. 232 (55%) patients in the hyperinflammatory group and 136 (29%) patients in the hypoinflammatory group died within 60 days (p<0·0001). The effects on 60-day mortality were more pronounced among patients with the hypoinflammatory phenotype than the hyperinflammatory phenotype for high respiratory system driving pressure (≥15 cm H
2. Surfactant use and outcomes in middle-income versus high-income countries.
In 271,826 very low birth weight infants, surfactant use and timing varied markedly by income setting and sector: private MIC centers had the highest use (64.1%) and fastest administration (median 60 min), while public MIC centers had the lowest use (43.5%) and slowest timing (120 min). Survival after SRT was highest in HICs (88.1%) and lowest in public MIC centers (69.5%), with higher sepsis burden in MICs.
Impact: This study quantifies global inequities in access and timing of a life-saving therapy for neonatal RDS at unprecedented scale, linking systems factors to survival and sepsis.
Clinical Implications: For neonatal RDS, prioritizing early SRT access and delivery room CPAP uptake, especially in public MIC centers, could reduce mortality and sepsis. Health systems interventions (procurement, protocols, and training) should target timely administration within the first hour when indicated.
Key Findings
- Surfactant use: private MIC centers 64.1%, HICs 55.3%, public MIC centers 43.5%.
- Median time to first dose: private MIC 60 min vs public MIC 120 min; HICs used earlier surfactant with more delivery room CPAP.
- Post-SRT survival: highest in HICs (88.1%) and lowest in public MIC centers (69.5%); sepsis burden higher in MICs.
Methodological Strengths
- Very large, prospectively collected multicenter registry (Vermont Oxford Network)
- Stratified analysis by national income level and facility ownership capturing system-level effects
Limitations
- Observational secondary analysis with potential residual confounding and variable local protocols
- Limited granularity on illness severity and resource constraints; causality cannot be inferred
Future Directions: Implementation trials and health policy interventions to improve early SRT access in MIC public centers; benchmarking dashboards for time-to-surfactant and infection control.
Preterm birth remains a leading cause of neonatal mortality, disproportionately affecting low-and middle-income countries (LMICs). Surfactant replacement therapy (SRT) is a key intervention for neonatal respiratory distress syndrome (RDS). However, due to cost and differing guidelines there are likely differences in SRT in different parts of the world. This study compared surfactant use, timing of administration, and associated neonatal outcomes in very low birth weight (VLBW) infants born in high-income countries (HICs) versus middle-income countries (MICs), with further analysis of public and private centers within MICs. This secondary analysis of prospectively collected data using the Vermont Oxford Network database included 271 826 inborn VLBW infants from 2018 to 23. Data were stratified by country income classification and ownership (public center vs. private center) in MICs. Surfactant use was highest in private MIC centers (64.1%), followed by HICs (55.3%), and public MIC centers (43.5%). Median time to first surfactant dose was shortest in private MIC centers (60 min) and longest in public MIC centers (120 min). Infants in HICs were more likely to receive delivery room continuous positive airway pressure and earlier surfactant. Survival post-SRT was highest in HICs (88.1%) and lowest in public MIC centers (69.5%) with sepsis being a particular problem in MICs. Disparities in the proportion of infants receiving SRT, the timing of doses, and neonatal outcomes such as mortality and sepsis rates persist between HICs and MICs, and between public and private sectors in MICs.
3. Surfactant retreatment in very preterm infants with respiratory distress syndrome: an observational cohort study.
In a retrospective cohort of 140 very preterm infants with RDS, 39% received a single surfactant dose and 61% received multiple doses. Oxygenation improved after both the first and second doses, supporting the physiological effectiveness of retreatment when clinically indicated.
Impact: Fills a guidance gap by quantifying oxygenation responses to sequential surfactant doses, informing retreatment decisions in very preterm infants.
Clinical Implications: For neonatal RDS, clinicians may consider a second surfactant dose guided by objective oxygenation indices and clinical trajectory when initial response is incomplete.
Key Findings
- Among 140 very preterm infants, 39% received one surfactant dose and 61% received multiple doses.
- Oxygenation (SpO2) improved after the first and second surfactant administrations.
- Addresses a lack of guideline direction by reporting physiological response to retreatment.
Methodological Strengths
- Clearly defined clinical question focused on retreatment effectiveness
- Real-world cohort including both single- and multiple-dose exposures
Limitations
- Retrospective single-setting analysis with limited sample size
- Lack of standardized retreatment criteria and potential confounding by illness severity
Future Directions: Prospective studies to define standardized retreatment thresholds integrating oxygenation metrics, lung ultrasound/radiography, and noninvasive ventilation parameters.
BACKGROUND: Data on surfactant retreatment in preterm infants with respiratory distress syndrome (RDS) are limited, and international guidelines do not provide specific recommendations on this issue. The objective of this study was to evaluate the effectiveness of surfactant retreatment in very preterm infants (VPI). METHODS: We retrospectively studied 140 VPI born at 23 RESULTS: Fifty-four (39%) infants received one dose of surfactant and 86 (61%) multiple doses. SpO CONCLUSIONS: The first and second doses of surfactant were effective in improving SpO