Daily Respiratory Research Analysis
A phase 3 randomized trial (SESAR) found inhaled sevoflurane sedation led to fewer ventilator-free days and lower 90-day survival than intravenous propofol in ARDS, indicating potential harm. Metatranscriptomic profiling of pediatric acute sinusitis/URI captured both pathogens and host-response signatures with high concordance to standard tests and suggested diagnostic biomarkers. Mechanistic work in mice showed platelet 12-lipoxygenase deficiency worsens SARS-CoV-2 lung inflammation, highlighti
Summary
A phase 3 randomized trial (SESAR) found inhaled sevoflurane sedation led to fewer ventilator-free days and lower 90-day survival than intravenous propofol in ARDS, indicating potential harm. Metatranscriptomic profiling of pediatric acute sinusitis/URI captured both pathogens and host-response signatures with high concordance to standard tests and suggested diagnostic biomarkers. Mechanistic work in mice showed platelet 12-lipoxygenase deficiency worsens SARS-CoV-2 lung inflammation, highlighting a lipid pathway target.
Research Themes
- Sedation strategies and outcomes in ARDS
- Metatranscriptomic diagnostics for pediatric respiratory infections
- Platelet lipid metabolism in viral lung inflammation
Selected Articles
1. Inhaled Sedation in Acute Respiratory Distress Syndrome: The SESAR Randomized Clinical Trial.
In this phase 3 randomized, assessor-blinded trial of 687 ARDS patients, inhaled sevoflurane sedation led to fewer ventilator‑free days by day 28 and lower 90‑day survival compared with intravenous propofol. Early 7‑day mortality and ICU‑free days were also worse with sevoflurane.
Impact: This high‑quality RCT directly informs sedation choice in ARDS and indicates potential harm with inhaled sevoflurane. The negative but definitive findings can change ICU practice and guidelines.
Clinical Implications: For moderate-to-severe ARDS requiring deep sedation, prioritize intravenous propofol over inhaled sevoflurane outside of research protocols; review institutional sedation pathways and device availability. Monitor for early mortality risk when using inhaled agents.
Key Findings
- Sevoflurane resulted in fewer ventilator‑free days at day 28 vs propofol (median difference −2.1 days, 95% CI −3.6 to −0.7).
- 90‑day survival was lower with sevoflurane (47.1%) than propofol (55.7%; HR 1.31, 95% CI 1.05–1.62).
- Higher 7‑day mortality and fewer ICU‑free days through day 28 occurred with sevoflurane.
Methodological Strengths
- Phase 3 multicenter randomized design with assessor blinding
- Prespecified primary and key secondary endpoints with adequate sample size (n=687)
Limitations
- Open-label to treating teams may introduce performance bias
- Results reflect French ICUs and device availability; generalizability to other settings may vary
Future Directions: Conduct pragmatic trials on sedation bundles incorporating analgesia-first strategies; explore mechanistic reasons for harm with volatile agents in ARDS (e.g., alveolar inflammation, hemodynamics).
2. Metatranscriptomic profiling reveals pathogen and host response signatures of pediatric acute sinusitis and upper respiratory infection.
Untargeted RNA-seq of nasopharyngeal samples from 221 children achieved high sensitivity/specificity for common bacterial and viral pathogens versus culture/qRT‑PCR, detected additional untested pathogens, and reconstructed 196 viral genomes. Host-expression signatures distinguished bacterial from viral infections, nominating hundreds of diagnostic biomarker candidates.
Impact: This study integrates pathogen detection with host-response profiling at scale, creating a unique dataset and revealing actionable biomarker candidates for distinguishing bacterial from viral pediatric URIs.
Clinical Implications: While not yet ready for routine care, metatranscriptomic diagnostics could reduce unnecessary antibiotics by resolving viral vs bacterial etiologies; host-response markers may be translated into rapid assays.
Key Findings
- RNA-seq showed 87%/81% sensitivity/specificity for three AS‑associated bacteria and 86%/92% for 12 respiratory viruses vs clinical tests.
- Detected 22 additional pathogens not clinically tested and identified plausible agents in 58% of otherwise negative cases.
- Reconstructed 196 viral genomes (including novel strains) and defined host-response signatures distinguishing bacterial vs viral infections.
Methodological Strengths
- Parallel benchmarking against both culture and qRT‑PCR across 221 pediatric cases
- Dual profiling of pathogen reads and host transcriptome enabling biomarker discovery
Limitations
- Single time‑point sampling; no prospective clinical utility assessment or impact on antibiotic prescribing
- Cost, turnaround time, and bioinformatics infrastructure remain barriers for routine deployment
Future Directions: Prospective validation in pragmatic trials linking RNA‑seq outputs to antibiotic decisions; translate host‑response gene sets into rapid point‑of‑care assays.
3. Deficiency in platelet 12-lipoxygenase exacerbates inflammation and disease severity during SARS-CoV-2 infection.
In mice lacking platelet 12‑LOX, SARS‑CoV‑2 infection caused greater lung inflammation, altered platelet/lung transcriptomes (including NLRP1‑linked genes), decreased protective 12‑HETrE, and worse survival vs wild‑type. Platelet lipid enzymatic pathways modulate COVID‑19 severity.
Impact: Identifies platelet 12‑LOX–derived lipids as modulators of lung inflammation and survival in SARS‑CoV‑2 infection, suggesting a tractable therapeutic axis in viral respiratory disease.
Clinical Implications: Although preclinical, results caution against indiscriminate inhibition of platelet 12‑LOX in COVID‑19 and support exploring lipid‑mediator–based therapies to mitigate hyperinflammation.
Key Findings
- Platelet 12‑LOX deficiency increased lung inflammation, leukocyte infiltrates, cytokines, and reduced survival after SARS‑CoV‑2 infection in mice.
- Transcriptomic changes included NLRP1 inflammasome–related pathways in platelets and lungs.
- Lipidomics showed reduced 12‑HETrE levels inversely correlated with disease severity.
Methodological Strengths
- Integrated histopathology, transcriptomics, and lipidomics across platelet and lung compartments
- Genetic model enabling causal inference for the 12‑LOX pathway
Limitations
- Findings are in murine models; human translational relevance requires validation
- Specificity to SARS‑CoV‑2 vs generalizable to other respiratory viruses remains to be defined
Future Directions: Validate platelet 12‑LOX signatures and lipid mediators in human COVID‑19 cohorts; explore pharmacologic modulation of 12‑LOX–derived lipids as adjunctive therapy.