Daily Ards Research Analysis
Analyzed 13 papers and selected 3 impactful papers.
Summary
Three ARDS-focused studies advance precision support and stratification. A translational physiology study shows that PEEP’s benefits and harms are region-dependent and detectable by EIT. A meta-analysis suggests prolonged prone positioning improves oxygenation without confirmed survival benefit and may increase pressure injuries, while pediatric nasal methylomics identifies two epigenetic subgroups with divergent clinical trajectories.
Research Themes
- EIT-guided, regionally personalized ventilation and PEEP titration
- Trade-offs of prolonged prone positioning in ARDS
- Epigenetic endotyping in pediatric ARDS for precision medicine
Selected Articles
1. Global vs. regional effects of PEEP on recruitment and strain: Insights from Preclinical and Clinical Studies.
In porcine ALI and human ARDS (mixed and COVID-19), dorsal lung regions showed the highest recruitability, while increasing PEEP reduced ventral dynamic strain but could paradoxically increase dorsal strain, especially in less recruitable lungs. Electrical impedance tomography detected these regional patterns and predicted paradoxical dorsal strain using a ventral-to-dorsal ventilation shift metric.
Impact: This translational study links global recruitability to regional strain behavior and provides an EIT-based signal to anticipate harmful strain during PEEP titration.
Clinical Implications: PEEP titration should be individualized using bedside EIT to balance recruitment and overdistension; in low-recruitability lungs, high PEEP may increase dorsal strain despite global improvements.
Key Findings
- Global recruitability ranked: symmetrical ALI pigs highest (R/I 1.39 [1.04–1.66]), then mixed ARDS (1.06 [0.70–1.23]), COVID-19 ARDS (0.66 [0.51–0.98]), asymmetrical ALI pigs lowest (0.45 [0.22–0.85]).
- Dorsal regions had the highest recruitability (p=0.001) and greater dorsal–ventral differences in more recruitable subjects.
- Increasing PEEP decreased ventral dynamic strain (p<0.01) but could paradoxically increase dorsal strain due to ventral hyperinflation, more often in less recruitable lungs.
- EIT metrics (ventral-to-dorsal shift normalized to dorsal volume change) predicted paradoxical dorsal strain (p<0.001).
Methodological Strengths
- Integrated preclinical porcine models with human ARDS cohorts for translational inference
- Standardized derecruitment maneuver with R/I ratio and regional EIT to quantify recruitability and strain
Limitations
- Non-randomized design; moderate sample sizes and potential selection bias
- EIT spatial resolution limits and single-breath maneuvers may not reflect long-term dynamics
Future Directions: Prospective trials testing EIT-guided PEEP titration stratified by recruitability; validation of EIT-derived strain predictors against outcomes and imaging.
In Acute Respiratory Distress Syndrome (ARDS), regional aeration is often gravity-dependent, with Positive End-Expiratory Pressure (PEEP) recruiting the lung dorsally. While recruitability can be assessed globally, our aim was to determine the impact of PEEP on regional recruitability and regional strain. To achieve a large representation of recruitability, we studied two preclinical porcine models of acute lung injury ([ALI] 19 symmetrical and 10 asymmetrical ALI), 20 patients with ARDS of mixed etiology (mixed ARDS) and 15 with COVID-19 ARDS. All study subjects underwent a single-breath derecruitment maneuver from high to low PEEP to quantify recruitability using the recruitment-to-inflation ratio (R/I). The regional effects of PEEP on strain were assessed using Electrical Impedance Tomography (EIT). Symmetrical ALI animals had the highest R/I (1.39[1.04-1.66]), followed by mixed ARDS (1.06[0.70-1.23]), COVID-19 ARDS (0.66[0.51-0.98]), and asymmetrical ALI (0.45[0.22-0.85]). Dorsal regions had the highest recruitability (p=0.001), and differences between dorsal and ventral regions were higher in recruitable subjects. Increasing PEEP decreased ventral dynamic strain (p<0.01), with varying effects on dorsal dynamic strain. A paradoxical increase in dorsal dynamic strain associated with ventral hyperinflation could be observed across all groups, but more frequently in the less recruitable subjects. It was predicted by the EIT ventral-to-dorsal shift in ventilation normalized to the change in dorsal lung volume (p<0.001). In animals and patients with varying recruitability, a higher global R/I is associated with a higher effect on the dorsal versus ventral R/I. PEEP can paradoxically increase dorsal strain due to ventral overdistention, and this is detectable by EIT.
2. Clinical benefits of prolonged versus standard prone positioning in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: A systematic review, meta-analysis, and trial-sequential analysis.
Across 7 studies (n=996), prolonged prone sessions (>24 h) in COVID-19 ARDS improved oxygenation during and after sessions but did not demonstrate a significant mortality benefit and showed a borderline increase in pressure injuries. Trial sequential analysis indicates that current evidence is underpowered to confirm benefit or harm.
Impact: This synthesis clarifies the current evidence balance for prolonged prone positioning, highlighting improved oxygenation but uncertain survival and safety signals that warrant definitive RCTs.
Clinical Implications: Clinicians should individualize prone session duration, weighing oxygenation gains against pressure injury risk, and avoid assuming mortality benefit until high-quality RCTs are available.
Key Findings
- Seven studies (6 observational, 1 RCT; n=996) compared >24 h vs ≤24 h prone sessions in COVID-19 ARDS.
- Mortality: RR 0.81 (95% CI 0.60–1.09; P=0.16) favoring prolonged prone, not statistically significant.
- Pressure injuries: RR 1.27 (95% CI 1.00–1.62; P=0.05), borderline increase with prolonged sessions.
- Oxygenation improved during (PaO2/FiO2 MD +17.42 mmHg; P=0.003) and after prone positioning (MD +23.83 mmHg; P=0.008); ICU length of stay and ventilatory pressures unchanged.
- Trial sequential analysis indicates insufficient information size to confirm benefit or harm.
Methodological Strengths
- Systematic review and meta-analysis with predefined exposure threshold and inclusion of both RCT and observational studies
- Trial sequential analysis to assess information size and conclusiveness
Limitations
- Predominance of observational studies with potential confounding and heterogeneity in proning protocols
- COVID-19-specific population limits generalizability to non-COVID ARDS; possible publication bias not excluded
Future Directions: Well-powered, pre-registered RCTs testing session duration with standardized skin protection bundles and patient-centered outcomes, ideally stratified by recruitability/phenotype.
OBJECTIVES: The optimal duration of prone positioning for improving outcomes in acute respiratory distress syndrome remains uncertain. This meta-analysis compared clinical outcomes of prolonged versus standard prone positioning in adult coronavirus disease 2019 patients with moderate-to-severe acute respiratory distress syndrome. METHODS: PubMed, SCOPUS, and Cochrane databases were systematically searched for randomised controlled trials (RCTs) and observational studies. Prolonged prone positioning was defined as a mean duration >24 h per session and standard as ≤ 24 h. Outcomes included mortality, pressure injuries, oxygenation, and respiratory parameters. A trial sequential analysis was conducted for mortality and pressure injuries. RESULTS: Seven studies (six observational and one RCT) involving 996 patients (592 prolonged and 404 standard) were included in the study. Prolonged prone positioning showed a nonsignificant trend towards lower mortality (33.8% vs. 39.8%, RR: 0.81, 95% confidence interval: 0.60-1.09; P = 0.16) and a borderline increase in pressure injuries (30.2% vs. 26.2%; relative risk (RR) 1.27, 95% confidence interval: 1.00-1.62; P = 0.05). The trial sequential analysis indicated that current evidence is insufficient to confirm benefit or harm. No significant differences were observed in intensive care unit length of stay (mean difference [MD]: 2.74 days; P = 0.13) or changes in positive end-expiratory pressure or driving pressure in both groups. Oxygenation improved significantly during (partial pressure of arterial oxygen-to-fraction of inspired oxygen ratio MD: 17.42 mmHg; P = 0.003) and after prone positioning (partial pressure of arterial oxygen-to-fraction of inspired oxygen ratio MD: 23.83 mmHg; P = 0.008). CONCLUSION: Prolonged prone positioning was associated with trends towards lower mortality and higher frequency of pressure injury risk, but evidence remains inconclusive. While oxygenation improved, clinical outcomes of intensive care unit length of stay and respiratory parameters were unchanged. Additional high-quality RCTs are needed to clarify the balance of benefits and risks and guide future recommendations.
3. Methylomic Analysis of Nasal Brushings Reveals Two Subgroups in Pediatric Acute Respiratory Distress Syndrome.
In a prospective single-center cohort, day-1 nasal methylomes in PARDS revealed two epigenetic subgroups differentiated by methylation of immune, repair, and regeneration gene regions. One subgroup trended toward worse outcomes, suggesting early, noninvasive endotyping may enable risk stratification and targeted therapy development.
Impact: Introduces a practical, airway-accessible epigenetic biomarker approach to identify PARDS subgroups at admission, addressing biological heterogeneity that hinders trials.
Clinical Implications: Nasal methylomics could inform early risk stratification and enrollment in phenotype-targeted trials; eventual methylation-guided therapies might emerge if validated.
Key Findings
- Prospective PICU cohort with day-1 nasal brushing methylomes identified two PARDS clusters by PCA and hierarchical clustering.
- Clusters were defined by differential methylation in promoters and gene bodies involved in immune, repair, and regeneration pathways.
- One epigenetic subgroup trended toward worse clinical outcomes; the other resembled controls.
Methodological Strengths
- Prospective design with sampling at a uniform early time point (day 1) and concurrent clinical outcome collection
- Unsupervised clustering with methylome-wide assessment enabling unbiased subgroup discovery
Limitations
- Single-center study with unspecified sample size; external validity uncertain
- Preprint status; lack of replication and mechanistic validation; potential confounders (e.g., etiology, therapies) not fully addressed
Future Directions: Multi-center validation cohorts, integration with transcriptomics/proteomics, and testing whether methylation-defined subgroups predict response to targeted interventions.
Pediatric acute respiratory distress syndrome (PARDS) is a significant cause of mortality in the pediatric intensive care unit (PICU), and supportive care remains the mainstay of treatment. The biological heterogeneity of PARDS hampers the development of new therapies. One source of heterogeneity is the epigenetic regulation of gene expression via methylation. We hypothesized that PARDS patients could be classified into at least two subgroups defined by differential methylation of immune-related genes. We conducted a prospective, single-center cohort study of PARDS and control patients under 18 years of age admitted to the PICU. Nasal brushings were obtained on day 1 for methylomic analysis, and clinical information and outcomes were recorded until discharge. We identified two groups of PARDS subjects using PCA and hierarchical clustering, which were defined by the differential methylation of promoters and bodies of genes involved in immune, repair, and regeneration processes. One group trended toward worse clinical outcomes. The other group had a methylation pattern very similar to control subjects. PARDS patients can be divided into two subgroups based on patterns of differential methylation around genes involved in immune, repair, and regeneration processes. These findings, if confirmed, could represent potential targets for future therapies.