Daily Ards Research Analysis
Three studies advance ARDS-related science across physiology, biomarkers, and endothelial biology. A prospective intraoperative study shows the recruitment-to-inflation (R/I) ratio tracks recruitability and optimal PEEP; a proteomics case series proposes a serum signature predicting response to MSC therapy in COVID-19 ARDS; and endothelial circRNA profiling implicates MAPK signaling and shear-stress pathways in barrier dysfunction.
Summary
Three studies advance ARDS-related science across physiology, biomarkers, and endothelial biology. A prospective intraoperative study shows the recruitment-to-inflation (R/I) ratio tracks recruitability and optimal PEEP; a proteomics case series proposes a serum signature predicting response to MSC therapy in COVID-19 ARDS; and endothelial circRNA profiling implicates MAPK signaling and shear-stress pathways in barrier dysfunction.
Research Themes
- Personalized ventilation and lung recruitability assessment
- Biomarker-driven stratification for ARDS therapeutics
- Endothelial barrier dysfunction and noncoding RNA networks
Selected Articles
1. Evaluation of the Potential for Lung Recruitment with the Recruitment-to-Inflation Ratio during General Anesthesia.
In 20 surgical patients, the recruitment-to-inflation (R/I) ratio derived from a single-breath PEEP-release maneuver correlated with recruitable volume by tomography (r=0.82) and gas dilution (r=0.48). Patients with higher R/I (>0.40) required higher optimal PEEP and experienced greater reductions in dead space, regional collapse, and dynamic strain, supporting R/I as a bedside tool to individualize PEEP.
Impact: Provides a practical, equipment-free metric to stratify intraoperative recruitability and guide safer PEEP titration. Bridges ARDS physiology to perioperative care with multimodal validation.
Clinical Implications: R/I ratio can help identify patients who benefit from higher PEEP while minimizing overdistension, supporting individualized ventilation during general anesthesia.
Key Findings
- R/I correlated with recruitable volume normalized to FRC by gas dilution (r=0.48; slope 0.27 [0.03, 0.52]).
- R/I strongly correlated with recruited volume relative to PEEP-induced inflation by EIT tomography (r=0.82; slope 1.2 [0.77, 1.64]).
- High R/I (>0.40) required higher optimal PEEP (10 vs 8 cmH2O; P=0.03) and showed greater decreases in dead space (P=0.013), regional collapse (P=0.016), and dynamic lung strain (P=0.04).
Methodological Strengths
- Prospective physiologic protocol with multimodal measurements (EIT, gas dilution, ventilator waveforms).
- Standardized single-breath PEEP-release maneuver enabling bedside R/I calculation.
Limitations
- Small, single-center sample (N=20) without clinical outcome endpoints.
- Conducted in anesthetized surgical patients; generalizability to ICU ARDS requires testing.
Future Directions: Validate R/I-guided PEEP strategies in larger perioperative and ICU cohorts with clinical outcomes, and integrate with automated ventilator decision support.
BACKGROUND: During general anesthesia, the effect of positive end-expiratory pressure (PEEP) on lung injury depends on the potential for lung recruitment, which is variable among patients. The recruitment-to-inflation ratio (R/I) is measured from ventilator data during a single-breath PEEP-release maneuver and has been proposed to assess recruitability without the need for additional equipment during acute respiratory distress syndrome. This study hypothesized that R/I reliably estimates the individual potential for lung recruitment during general anesthesia. METHODS: Twenty patients undergoing open abdominal surgery received mechanical ventilation with PEEP of 12 cm H 2 O for 30 min, which was then abruptly reduced to 2 cm H 2 O. Finally, a decremental PEEP trial was performed to measure collapse and overdistension at each level. Gas exchange, end-tidal carbon dioxide, respiratory mechanics by ventilator waveform analysis, regional overdistension and collapse by electrical impedance tomography, end-expiratory lung volume, and functional residual capacity by nitrogen dilution were measured. The R/I was calculated during the single-breath derecruitment maneuver from ventilator data. RESULTS: The R/I (median = 0.41, range = 0 to 0.86) was linearly correlated with recruited volume normalized to functional residual capacity measured by gas dilution (r = 0.48, slope = 0.27 [0.03, 0.52]), and recruited volume scaled to PEEP-induced inflation volume measured by tomography (r = 0.82, slope = 1.2 [0.77, 1.64]). Compared to patients with R/I of less than or equal to 0.40 (n = 10), those with R/I greater than 0.40 (n = 10) required higher PEEP to optimize regional mechanics and balance collapse and overdistension (median [quartile 1, quartile 3]: 10 [8, 11] cm H 2 O vs . 8 [7, 9]; P = 0.03) and showed decreases in dead space (-2 [-5, 1] % vs . 3 [0, 5]%; P = 0.013) and greater reductions in collapse (-44 [-31, -47] % vs . -30 [-20, -38]%; P = 0.016) and dynamic lung strain (-0.06 [-0.09, -0.05] vs . -0.04 [-0.05, -0.02]; P = 0.04) with higher PEEP. CONCLUSIONS: During general anesthesia, the R/I reflects potential for lung recruitment. The R/I may help identify patients in whom higher PEEP improves physiology and may favor less injurious ventilation.
2. Personalized serum proteome profiles of COVID-19-associated acute respiratory distress syndrome in response to mesenchymal stem cell therapy.
In five COVID-19 ARDS patients receiving compassionate placenta-derived MSCs, paired serum proteomics revealed differential activation of inflammation, coagulation, and metabolism depending on ventilatory support. A candidate panel (CD44, MMP2, MMP9, CRP) is proposed to distinguish responders and guide patient selection.
Impact: Introduces a personalized proteomic approach to stratify MSC therapy response in ARDS, offering a testable biomarker panel to improve trial design and patient selection.
Clinical Implications: If validated, the CD44/MMP2/MMP9/CRP panel could support selecting ARDS patients most likely to benefit from MSCs and enable response monitoring.
Key Findings
- Paired proteomics before/after pc-MSC infusion showed improved lung injury clinically.
- Inflammation, coagulation, and glucose metabolism pathways were activated in invasively ventilated patients but inhibited in those on high-flow oxygen.
- Complement and HIF1α signaling upregulation suggested links to fibrosis risk.
- A serum panel (CD44, MMP2, MMP9, CRP) was proposed to discriminate treatment response.
Methodological Strengths
- Within-patient paired pre/post design enhances signal detection with limited N.
- Quantitative serum proteomics aligned with clinical phenotypes and ventilatory support.
Limitations
- Very small, uncontrolled compassionate-use case series (N=5) limits inference.
- Short-term molecular readouts without long-term outcomes or external validation.
Future Directions: Prospective controlled trials with serial proteomics to validate the panel and define predictive thresholds; integrate with imaging and lung mechanics for multi-omic stratification.
BACKGROUND: Mesenchymal stem cell (MSC) therapy is one of the therapeutic options for COVID-19-related acute respiratory distress syndrome (ARDS). However, not all patients benefit equally and the mechanism of action of the treatment remains unknown. Herein, we aimed to elucidate the molecular response to MSC treatment in COVID-19-related ARDS, and proposed protein signature to advocate for patient selection to maximize the benefit. METHOD: Five COVID-19-related ARDS patients who consented to compassionate placenta-derived (pc)-MSC treatment were followed for clinical response and disease progression. Serum samples were collected before and after pc-MSC infusion for quantitative proteomics analysis. RESULTS: Following treatment, lung injury was significantly improved. Patients with invasive mechanical ventilation exhibited activation of inflammation, coagulation, and glucose metabolism, while it was inhibited in patients with high-flow oxygenation maintenance. Upregulations of complement system and HIF1α signaling may suggest a correlation to lung fibrosis. We proposed CD44, MMP2, MMP9, and CRP as a distinction panel to advise the response to pc-MSC treatment. CONCLUSION: We exploited molecular regulations in response to pc-MSC treatment for COVID-19-related ARDS and proposed protein signatures to assist treatment decisions. Large cohort study to observe the long-term impact should be implemented in the future.
3. Transcriptome sequencing showed the differential expression of circRNAs in human pulmonary microvascular endothelial cells in acute respiratory distress syndrome.
Endothelial transcriptomics in ARDS revealed 379 upregulated and 448 downregulated circRNAs, implicating DNA damage responses and MAPK signaling. ceRNA network analysis linked differentially expressed circRNAs to shear stress response, angiogenesis, vascular development, and cell adhesion, highlighting candidates for barrier regulation and early biomarkers.
Impact: Provides a systems-level map of endothelial circRNA dysregulation in ARDS, pointing to mechanistic pathways of permeability and candidate biomarkers/targets.
Clinical Implications: While preclinical, the circRNA signatures may inform early ARDS prediction and endothelial-targeted therapies after validation.
Key Findings
- Identified 379 upregulated and 448 downregulated circRNAs in HPMECs under ARDS-related conditions.
- GO enrichment indicated roles in cellular response to DNA damage and repair.
- KEGG implicated MAPK signaling; ceRNA network linked targets to shear-stress response, angiogenesis, vascular development, and cell adhesion.
Methodological Strengths
- Comprehensive transcriptome-wide circRNA profiling with functional enrichment analyses.
- Integration of ceRNA network analysis to infer regulatory interactions.
Limitations
- Incomplete methodological details and lack of experimental validation for specific circRNA functions.
- In vitro endothelial model limits direct clinical extrapolation.
Future Directions: Validate top circRNA candidates in patient samples and in vivo models; perturbation experiments to test effects on endothelial permeability and ARDS outcomes.
BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by elevated pulmonary microvascular permeability; however, the role of circular RNAs (circRNAs) in this process remains unclear. Our study aims to discover the mechanism underlying the role of circRNA in pulmonary microvascular permeability in ARDS. METHODS: We developed an RESULTS: The genome sequencing results identified 379 significantly upregulated circRNAs and 448 significantly downregulated circRNAs. The 10 circRNAs with the greatest degree of upregulation and the 10 circRNAs with the greatest degree of downregulation were identified. The GO enrichment analysis results indicated that differential circRNA expression may mediate the cellular response to DNA damage, including DNA repair. The KEGG analysis results indicated that the mechanism by which differential circRNA expression exerts these effects may involve the mitogen-activated protein kinases (MAPK) signaling pathway. The GO enrichment analysis of the target genes in the ceRNA network showed that the circRNAs were mainly involved in the fluid shear stress response, angiogenesis regulation, vascular development, and cell adhesion. CONCLUSIONS: The differential expression of circRNAs may play an important role in ARDS, especially in the control of HPMEC permeability. The circRNAs that were shown to have differential expression in response to vascular development and shear stress response could be used as biomarkers for the early prediction of ARDS disease and potential future therapeutic targets.