Daily Ards Research Analysis
Three ARDS-related papers span biomarkers, supportive positioning, and inhaled prostacyclin therapy. NET surrogate markers in plasma (cfDNA, MPO-DNA) correlated with worse outcomes in moderate-to-severe ARDS, while multicenter real-world data examined gas-exchange changes after prone positioning. A narrative review concludes inhaled epoprostenol does not improve hard outcomes in invasively ventilated ARDS but may help select subgroups with pulmonary vascular disease.
Summary
Three ARDS-related papers span biomarkers, supportive positioning, and inhaled prostacyclin therapy. NET surrogate markers in plasma (cfDNA, MPO-DNA) correlated with worse outcomes in moderate-to-severe ARDS, while multicenter real-world data examined gas-exchange changes after prone positioning. A narrative review concludes inhaled epoprostenol does not improve hard outcomes in invasively ventilated ARDS but may help select subgroups with pulmonary vascular disease.
Research Themes
- Biomarkers and pathophysiology of ARDS (NETs, cfDNA, MPO-DNA)
- Prone positioning and gas exchange effects in ARDS
- Inhaled epoprostenol in acute hypoxemic respiratory failure and pulmonary hypertension
Selected Articles
1. Plasma surrogate markers of neutrophil extracellular traps correlate with disease severity in patients with moderate to severe acute respiratory distress syndrome.
In a secondary analysis of 200 non-COVID ARDS patients from the ROSE trial with serial sampling over 48 hours, plasma NET surrogates were elevated versus healthy controls and remained stable early after enrollment. Both cfDNA and MPO-DNA levels correlated with fewer ventilator-free days, and cfDNA uniquely correlated with higher mortality and illness severity.
Impact: This work links mechanistic NET biology to clinically relevant outcomes, supporting NETs as prognostic biomarkers in moderate-to-severe ARDS and motivating anti-NET therapeutic strategies.
Clinical Implications: Plasma cfDNA and MPO-DNA could help risk-stratify ARDS patients early in ICU care and serve as enrichment criteria for trials testing NET-targeted therapies; however, external validation and threshold standardization are needed before routine use.
Key Findings
- Plasma NET surrogates (cfDNA, MPO-DNA) were significantly higher in ARDS than in healthy controls.
- Marker levels remained largely unchanged over the first 48 hours after enrollment.
- Higher cfDNA and MPO-DNA were associated with fewer ventilator-free days; cfDNA also correlated with higher mortality and illness severity scores.
Methodological Strengths
- Nested analysis within an RCT cohort with adjudicated outcomes and standardized data capture (ROSE trial).
- Use of two orthogonal NET surrogates and inclusion of healthy controls; serial sampling at 0, 24, and 48 hours.
Limitations
- Secondary, retrospective biomarker-outcome correlation; causality cannot be inferred.
- Surrogate markers of NETs were used; limited to first 48 hours; generalizability to COVID-19 ARDS uncertain.
Future Directions: Prospective external validation, determination of clinically actionable thresholds, integration with multimodal biomarkers, and interventional trials of anti-NET strategies in enriched ARDS subgroups.
BACKGROUND: Although studies have evaluated the presence of cell-free DNA and neutrophil extracellular traps (NETs) in acute respiratory distress syndrome (ARDS), the kinetics of NET formation during the early ICU admission and whether plasma NET markers correlate with clinical outcomes in patients with moderate-to-severe hypoxemia remain unknown. We sought to determine whether serial plasma NET marker levels in study participants collected over 48 h post enrollment predict disease severity and mortality in non-COVID-19 ARDS patients. METHODS: We obtained previously collected plasma samples (trial enrollment, 24 h, 48 h) from 200 randomly selected ARDS participants in the completed Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) Trial, as well as from 20 healthy control donors. We determined plasma levels of surrogate biomarkers for NETs using a cell-free DNA fluorescence assay and a plasma myeloperoxidase (MPO)-DNA complex ELISA. We correlated these surrogate biomarker levels with clinical outcomes from the ROSE trial study participants. RESULTS: ROSE plasma samples demonstrated significantly higher NET levels compared to healthy donor controls. Individual study participant NET levels did not change over the forty-eight hours after trial enrollment. Higher levels of both surrogate markers correlated with fewer ventilator-free days, but only cell free-DNA correlated with mortality and higher illness severity scores. CONCLUSION: Surrogate markers for plasma NET levels measured in patients with moderate or severe ARDS correlate directly with adverse clinical outcomes and may serve as biomarkers for predicting severe disease. Further studies of surrogate biomarkers for NET formation in moderate-to-severe ARDS are warranted.
2. Inhaled epoprostenol for management of acute respiratory failure and pulmonary vascular disease.
This narrative review synthesizes pharmacology and clinical use of inhaled epoprostenol. It highlights lack of improvements in ventilator-free days, ICU length of stay, or mortality among invasively ventilated ARDS, while noting potential benefits in select populations, particularly those with pulmonary hypertension and right ventricular dysfunction.
Impact: Clarifies where inhaled epoprostenol adds value, guiding rational use as a physiologic adjunct and identifying subgroups for future trials.
Clinical Implications: Use inhaled epoprostenol as a rescue or adjunct in refractory hypoxemia with suspected pulmonary vascular dysfunction, and in ICU management of pulmonary hypertension; it should not be expected to improve mortality in ARDS without specific indications.
Key Findings
- Inhaled epoprostenol improves ventilation–perfusion matching while minimizing systemic adverse effects.
- Among invasively ventilated ARDS patients, it has not improved ventilator-free days, ICU length of stay, or mortality.
- Potential benefits exist in select populations, including those with pulmonary hypertension and right ventricular dysfunction.
Methodological Strengths
- Integrated pharmacologic overview with clinical application across ARDS and pulmonary hypertension.
- Synthesizes outcomes across multiple studies to contextualize benefits and limitations.
Limitations
- Narrative review without a pre-registered protocol or systematic bias assessment.
- Heterogeneity of included studies limits comparability and precludes meta-analytic effect estimates.
Future Directions: Conduct randomized or pragmatic trials in ARDS subgroups with pulmonary vascular dysfunction; compare inhaled epoprostenol vs nitric oxide; optimize dosing and aerosol delivery strategies.
Inhaled epoprostenol has remained an attractive and viable option for the delivery of prostacyclin to offset abnormalities in ventilation and perfusion mismatch while minimizing the typical adverse effects associated with systemic administration. There is a need to better understand pharmacologic properties of inhaled epoprostenol and its application to diseases affecting the cardiopulmonary system. The goal of this review is to provide an overview of inhaled epoprostenol and outline its use specifically in the medical management of acute hypoxemic respiratory failure and pulmonary vascular disease. Among patients with acute respiratory distress syndrome who ultimately required invasive ventilation, inhaled epoprostenol has not improved ventilator-free days, intensive care unit length of stay, or mortality. However, it may be beneficial in certain select patient populations. In the management of pulmonary hypertension, inhaled epoprostenol has allowed for continued maintenance of chronic pulmonary arterial hypertension-specific therapy and for possibly improving right ventricular function as an attractive option in the critical care management of pulmonary hypertension.
3. PaCO
A multicenter retrospective cohort from eight tertiary centers examined gas-exchange effects of prone positioning in moderate-to-severe ARDS, collecting arterial blood gases before and 24 hours after initiation. The cohort included 138 patients; analyses focused on PaCO2 and related gas-exchange parameters.
Impact: Provides real-world, multicenter data characterizing CO2-related gas-exchange responses to prone positioning, informing physiologic understanding and potential responder identification.
Clinical Implications: Characterizing PaCO2 and gas-exchange trajectories after prone positioning may help tailor ventilation strategies and identify patients who benefit most, though clinical decision-making requires complete results and prospective validation.
Key Findings
- Multicenter retrospective cohort spanning eight tertiary referral centers.
- Arterial blood gases collected before and 24 hours after prone positioning under supine conditions.
- A total of 138 ARDS patients undergoing prone positioning were included; analyses centered on PaCO2-related gas-exchange effects.
Methodological Strengths
- Multicenter design enhances generalizability and reflects real-world practice.
- Objective physiologic measurements (arterial blood gases) pre- and post-intervention.
Limitations
- Retrospective design with potential selection bias and missing data; incomplete abstract limits accessible outcome details.
- Heterogeneity in ventilator settings and prone protocols across centers may confound gas-exchange assessments.
Future Directions: Prospective multicenter studies to define PaCO2 trajectories and identify predictors of response to prone positioning, with standardized ventilator protocols.
BACKGROUND: Prone positioning has demonstrated decreased mortality in moderate to severe acute respiratory distress syndrome (ARDS) patients. This study aimed to investigate the gas exchange effect of prone positioning in moderate to severe ARDS patients. METHODS: This retrospective study includes eight tertiary referral centers. Demographic data, laboratory data, treatment records, ventilator setting data, and outcomes were collected. Arterial blood gas data were collected before and 24 h after the initiation of prone positioning and under the supine position. PaO RESULTS: One hundred thirty-eight patients receiving prone positioning were enrolled, with 86 (62.3 %) being PaO CONCLUSIONS: In this multicenter retrospective cohort study of patients with ARDS receiving prone positioning, PaCO