Weekly Ards Research Analysis
This week’s ARDS literature highlighted mechanistic advances linking metabolic reprogramming to endothelial dysfunction, precision diagnostic tools that map tissue injury noninvasively, and large-scale clinical evidence informing prevention strategies. A quantitative lactylome study identified ENO1 K193 lactylation as a nodal mechanism driving CXCL12 and endothelial injury. Plasma cfDNA methylomics in pediatric ARDS and a multicenter RSV vaccine effectiveness study (two seasons) point to transla
Summary
This week’s ARDS literature highlighted mechanistic advances linking metabolic reprogramming to endothelial dysfunction, precision diagnostic tools that map tissue injury noninvasively, and large-scale clinical evidence informing prevention strategies. A quantitative lactylome study identified ENO1 K193 lactylation as a nodal mechanism driving CXCL12 and endothelial injury. Plasma cfDNA methylomics in pediatric ARDS and a multicenter RSV vaccine effectiveness study (two seasons) point to translational diagnostics and prevention opportunities that may change clinical workflows.
Selected Articles
1. Global Lactylome Reveals Lactylation-Dependent Mechanisms Underlying CXC Motif Chemokine Ligand 12 Expression in Pulmonary Endothelium During Acute Respiratory Distress Syndrome.
Quantitative lactylome profiling linked elevated pulmonary lactate to lysine lactylation (Klac) of ENO1 at K193, which released translational repression of CXCL12 mRNA and increased ENO1 enzymatic activity, amplifying glycolysis and driving pulmonary endothelial dysfunction. Inhibition of lactylation attenuated chemokine release and mitigated experimental ARDS, connecting a metabolic post-translational modification to vascular injury.
Impact: Identifies a specific post-translational modification (ENO1 K193 lactylation) that causally links metabolism to chemokine-mediated endothelial injury, opening a directly druggable axis for endothelial protection in ARDS.
Clinical Implications: Supports development of therapies targeting lactylation or ENO1–CXCL12 signaling as adjunctive endothelial-protective strategies in ARDS; may inform biomarker selection for metabolic-targeted trials.
Key Findings
- Pulmonary lactate levels correlated with ARDS severity and prognosis.
- Lactate drives endothelial dysfunction via lysine lactylation; ENO1 K193 hyperlactylation identified by quantitative lactylomics.
- ENO1 K193 lactylation releases translational repression of CXCL12 and increases ENO1 enzymatic activity, amplifying glycolysis.
- Inhibiting lactylation reduced chemokine release and mitigated experimental ARDS.
2. Cell-free DNA methylomics identify tissue injury patterns in pediatric ARDS.
Plasma cell-free DNA methylation profiling was used to infer tissue-of-origin for injury in pediatric ARDS, enabling objective mapping of which organs are affected. This noninvasive approach can stratify patients by organ involvement and suggest targeted interventions or monitoring strategies.
Impact: Introduces a scalable, noninvasive precision-diagnostic platform that can deconvolute multiorgan injury in ARDS—critical for phenotype-driven therapies and trial enrichment in pediatric populations.
Clinical Implications: cfDNA methylome panels could guide risk stratification, targeted organ support, and enrollment criteria for trials testing organ-specific interventions in pediatric ARDS; prospective validation is needed.
Key Findings
- Plasma cfDNA methylation signatures can identify tissue injury patterns in children with severe lung injury/ARDS.
- This method provides objective, noninvasive mapping of organ involvement that can inform targeted therapies.
3. RSV Vaccine Effectiveness Against Hospitalization Among US Adults Aged 60 Years or Older During 2 Seasons.
A 26-hospital, test-negative case-control study across two RSV seasons (2023–24 and 2024–25) including 6,958 adults ≥60 years found overall vaccine effectiveness against RSV-associated hospitalization of 58%, with 69% effectiveness for same-season vaccination. Effectiveness was substantially lower in immunocompromised individuals and those with cardiovascular disease, informing prioritization and revaccination interval questions.
Impact: Large, multicenter effectiveness data across two seasons directly informs public health vaccination policy, booster timing, and risk-group prioritization to reduce severe respiratory illness and potential downstream ARDS.
Clinical Implications: Supports use of RSV vaccination in older adults to reduce hospitalizations; prompts consideration of earlier or alternative strategies in immunocompromised patients and targeting vaccination campaigns to reduce ARDS risk in vulnerable populations.
Key Findings
- Overall vaccine effectiveness against RSV-associated hospitalization was 58% across two seasons.
- Same-season vaccination effectiveness 69% vs prior-season 48%; effectiveness lower in immunocompromised (30%) and those with cardiovascular disease.
- Large test-negative, multicenter design (N=6,958) with stratified, adjusted analyses.