Daily Respiratory Research Analysis
Key advances span clinical, mechanistic, and data-resource fronts in respiratory medicine. A large multicenter JAMA RCT found that driving pressure–guided high PEEP with recruitment maneuvers did not reduce postoperative pulmonary complications versus standard low PEEP, while increasing intraoperative hypotension. Mechanistically, Science Translational Medicine reports that disrupted proteostasis in alveolar type 2 cells drives fibrogenic MIF–CD74 signaling to macrophages, and a Nucleic Acids Re
Summary
Key advances span clinical, mechanistic, and data-resource fronts in respiratory medicine. A large multicenter JAMA RCT found that driving pressure–guided high PEEP with recruitment maneuvers did not reduce postoperative pulmonary complications versus standard low PEEP, while increasing intraoperative hypotension. Mechanistically, Science Translational Medicine reports that disrupted proteostasis in alveolar type 2 cells drives fibrogenic MIF–CD74 signaling to macrophages, and a Nucleic Acids Research resource (ResMicroDb) aggregates 106k+ respiratory microbiome samples with standardized processing and cross-study tools.
Research Themes
- Perioperative ventilation strategies and postoperative pulmonary complication risk
- Epithelial–immune crosstalk and proteostasis in pulmonary fibrosis
- Standardized respiratory microbiome resources enabling cross-cohort analysis
Selected Articles
1. Dysregulated alveolar type 2 epithelial cell proteostasis promotes fibrogenic macrophage migration inhibitory factor-CD74 signaling.
Using multiple models, the authors demonstrate that disrupting the ubiquitin–proteasome system in AEC2s drives profibrotic macrophage signaling via MIF family proteins and CD74. The work implicates epithelial proteostasis as an upstream regulator of MIF–CD74 crosstalk in IPF pathogenesis and highlights this axis as a potential therapeutic target.
Impact: This study uncovers a previously unappreciated epithelial UPS–MIF–CD74 pathway that mechanistically links AEC2 proteostasis to fibrogenic macrophage activation in IPF. It opens a tractable therapeutic axis beyond conventional antifibrotic strategies.
Clinical Implications: Targeting MIF–CD74 signaling or restoring epithelial proteostasis in AEC2s may attenuate macrophage-driven fibrosis, offering new avenues for IPF treatment beyond current antifibrotic agents.
Key Findings
- AEC2-specific disruption of the ubiquitin–proteasome system amplifies profibrotic signaling toward macrophages.
- Macrophage migration inhibitory factor (MIF) family proteins and CD74 mediate the epithelial–macrophage crosstalk.
- Findings were consistent across several experimental models, supporting a generalizable mechanism.
Methodological Strengths
- Mechanistic dissection across several models, including epithelial cell–specific perturbation.
- Clear linkage of epithelial proteostasis to immune signaling via MIF–CD74 axis.
Limitations
- Abstract does not detail human validation or therapeutic intervention data.
- Specifics of the AEC2 cullin 3 model and downstream effectors beyond MIF–CD74 are truncated in the abstract.
Future Directions: Validate MIF–CD74 dependency in human IPF tissues and test pharmacologic modulation of MIF–CD74 or epithelial UPS pathways in preclinical models moving toward translational trials.
Aberrant proteostasis in alveolar type 2 epithelial cells (AEC2s) contributes to idiopathic pulmonary fibrosis (IPF), but the role of the ubiquitin-proteasome system (UPS) is unclear. Here, we show that UPS disruption in AEC2s amplifies profibrotic signaling to macrophages through macrophage migration inhibitory factor (MIF) family proteins in several models. Modeling UPS disruption with an AEC2-specific cullin 3 (
2. Intraoperative Driving Pressure-Guided High PEEP vs Standard Low PEEP for Postoperative Pulmonary Complications.
In 1435 high-risk adults undergoing open abdominal surgery, a strategy of driving pressure–guided high PEEP with recruitment maneuvers did not lower the incidence of postoperative pulmonary complications compared with standard low PEEP. High PEEP increased intraoperative hypotension and vasoactive use, while low PEEP had more transient desaturation events.
Impact: This definitive multicenter RCT challenges the presumed benefit of titrated high PEEP with recruitment in high-risk patients, informing perioperative ventilation protocols.
Clinical Implications: Standard low tidal volume ventilation with low PEEP remains appropriate for open abdominal surgery; routine use of high PEEP titrated to driving pressure with recruitment maneuvers should be reconsidered given lack of benefit and higher hypotension.
Key Findings
- Primary outcome (postoperative pulmonary complication composite) was similar: 19.8% (high PEEP) vs 17.4% (low PEEP), P=0.23.
- High PEEP increased intraoperative hypotension (54.0% vs 45.0%) and vasoactive agent use (32.0% vs 18.8%).
- Low PEEP group had more intraoperative desaturation events (2.8% vs 0.8%).
Methodological Strengths
- Large, multicenter randomized design with standardized low tidal volume ventilation.
- Clinically relevant composite endpoint with prespecified intraoperative safety outcomes.
Limitations
- Composite outcome may dilute effects on individual complications.
- Open-label intraoperative strategies could not be blinded; applicability to laparoscopic surgery is uncertain.
Future Directions: Identify subgroups (e.g., severe obesity, baseline atelectasis risk) that may benefit from higher PEEP, and refine individualized ventilation beyond PEEP titration (e.g., recruitment timing, monitoring).
IMPORTANCE: The effect of individualized high positive end-expiratory pressure (PEEP) and recruitment maneuvers, targeting a low driving pressure, on clinical outcomes in patients undergoing open abdominal surgery is uncertain. OBJECTIVE: To compare driving pressure-guided high PEEP and recruitment maneuvers with standard low PEEP without recruitment maneuvers with respect to postoperative pulmonary complications. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of 1435 adults at increased risk for postoperative pulmonary complications who were scheduled for open abdominal surgery. The trial was conducted at 29 sites in 5 countries across Europe from April 2019 to December 2024; final follow-up was in March 2025. Statistical analysis was conducted in May 2025. INTERVENTION: Patients were randomized to undergo intraoperative ventilation with driving pressure-guided high PEEP and recruitment maneuvers (n = 718) or to intraoperative ventilation with standard low PEEP (n = 717). All patients received low tidal volume ventilation. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including severe respiratory failure, bronchospasm, suspected pulmonary infection, pulmonary infiltrates, aspiration pneumonitis, atelectasis, acute respiratory distress syndrome, pleural effusion, cardiopulmonary edema, and pneumothorax. Among the 16 prespecified secondary outcomes, 4 concerned intraoperative complications, including hypotension (decrease in mean arterial pressure of >20% for >3 minutes) and desaturation (Spo2 <92% for >1 minute). RESULTS: Among 1468 adults, 1435 (98%) completed the trial (median [IQR] age, 66 [57-74] years; 52% female). In the primary analysis population, the primary outcome occurred in 142 of 718 patients (19.8%) in the driving pressure-guided high PEEP group compared with 125 of 717 patients (17.4%) in the low PEEP group (absolute difference, 2.5% [95% CI, -1.5% to 6.4%]; P = .23). The incidence of hypotension (382 [54.0%] vs 317 [45.0%]) and use of vasoactive agents (224 [32.0%] vs 130 [18.8%]) was higher in the high PEEP group; the incidence of intraoperative desaturation (6 [0.8%] vs 20 [2.8%]) was higher in the low PEEP group. CONCLUSIONS AND RELEVANCE: Among patients at increased risk for postoperative pulmonary complications undergoing open abdominal surgery under general anesthesia, intraoperative ventilation with driving pressure-guided high PEEP and recruitment maneuvers, compared with a strategy with standard low PEEP, did not reduce postoperative pulmonary complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03884543.
3. ResMicroDb: a comprehensive database and analysis platform for the human respiratory microbiome.
ResMicroDb aggregates 106,464 respiratory microbiome samples across 514 projects with standardized taxonomic profiling and curated metadata. It provides 11,908 microbe–disease associations and built-in tools for composition visualization, sample similarity search, and cross-study analysis, enabling reproducible, large-scale comparative studies.
Impact: As the largest curated respiratory microbiome repository with analysis utilities, ResMicroDb will underpin cross-cohort reproducibility, hypothesis generation, and biomarker discovery, likely becoming a widely cited community resource.
Clinical Implications: Standardized cross-study comparisons can accelerate identification of microbial signatures linked to respiratory diseases, informing diagnostics and potential microbiome-targeted interventions.
Key Findings
- Compiled 106,464 respiratory microbiome samples from 514 projects with standardized pipelines and 32 curated metadata fields.
- Reported 11,908 microbe–disease associations from 132 case–control studies.
- Provides three integrated analysis tools: composition visualization, sample similarity search, and cross-study analysis.
Methodological Strengths
- Large-scale harmonization with standardized bioinformatics workflows.
- Extensive manual curation of metadata to enhance interoperability and reuse.
Limitations
- Heterogeneity of source studies and platforms may introduce residual batch effects despite harmonization.
- Cross-sectional nature and variable clinical metadata depth may limit causal inference.
Future Directions: Incorporate longitudinal datasets, multi-omics layers (metagenomics, metabolomics), and standardized clinical phenotyping to enable causal modeling and translational applications.
The respiratory microbiome plays an important role in maintaining human health. Despite the rapid growth of literature and publicly accessible data on the respiratory microbiome, a large-scale, well-curated database is still lacking. Here, we introduced ResMicroDb, a comprehensive database and analysis platform for the human respiratory microbiome. ResMicroDb contains 106 464 samples from 514 projects, spanning 10 sample sites, 72 sample types, and 146 phenotypes. Notably, it includes ~7-fold more respiratory samples than existing multi-body-site resources. To improve the reusability and accessibility of data, a standardized bioinformatics pipeline was employed to generate taxonomic profiles, and 32 metadata fields were manually curated. ResMicroDb also provides 11 908 microbe-disease associations, identified from 132 case-control studies, to deepen the understanding of microbiome-disease relationships. Additionally, ResMicroDb offers three tools for in-depth analysis: "Microbiome Composition" for visualizing taxonomic profiles of user-selected samples; "Sample Similarity Search" for inferring the characteristics of new samples by comparing them to the database based on similarity; and "Cross-study Analysis" for identifying common and specific microbial characteristics across cohorts, phenotypes and sample sites. ResMicroDb serves as a versatile and valuable resource for advancing a broad spectrum of respiratory microbiome research and clinical relevance. ResMicroDb is freely accessed at https://resmicrodb.cncb.ac.cn.