Daily Ards Research Analysis
A multicentre randomized trial shows that multimodal prehabilitation, including high-intensity respiratory muscle training, significantly reduces postoperative pulmonary complications and shortens hospital stay after lung resection. Two ARDS-focused translational studies elucidate pathophysiologic mechanisms: longitudinal plasma/BALF proteomics highlights acute-phase B-cell signaling activation with suppressed HSP90 chaperone activity, while an integrative single-cell/transcriptomic analysis ide
Summary
A multicentre randomized trial shows that multimodal prehabilitation, including high-intensity respiratory muscle training, significantly reduces postoperative pulmonary complications and shortens hospital stay after lung resection. Two ARDS-focused translational studies elucidate pathophysiologic mechanisms: longitudinal plasma/BALF proteomics highlights acute-phase B-cell signaling activation with suppressed HSP90 chaperone activity, while an integrative single-cell/transcriptomic analysis identifies CD19 and GPR65 as sialylation-linked genes and CD14 monocytes as key cells in sepsis-induced ARDS.
Research Themes
- Prehabilitation reduces postoperative pulmonary complications
- B-cell and chaperone pathway dysregulation in ARDS pathophysiology
- Sialylation-linked immune signatures and key cell types in sepsis-induced ARDS
Selected Articles
1. Multimodal prehabilitation before lung resection surgery: a multicentre randomised controlled trial.
In high-risk patients scheduled for lung resection, multimodal prehabilitation (including high-intensity respiratory muscle training) reduced postoperative pulmonary complications from 55% to 34% and shortened hospital stay from 9 to 7 days. The trial was prospectively registered and multicentre, supporting generalizability.
Impact: This RCT provides actionable evidence that targeted prehabilitation improves postoperative pulmonary outcomes and resource utilization. It can inform perioperative pathways for thoracic surgery.
Clinical Implications: Incorporate structured, multimodal prehabilitation (with high-intensity respiratory muscle training) into preoperative care for high-risk lung resection candidates to reduce PPCs and hospital length of stay.
Key Findings
- Postoperative pulmonary complications were reduced with prehabilitation (34% vs 55%; OR 2.29; P=0.029).
- Hospital length of stay decreased from 9 to 7 days with prehabilitation (P=0.038).
- Intervention included high-intensity respiratory muscle training as part of a multimodal program.
Methodological Strengths
- Prospective, multicentre randomized controlled design with trial registration (NCT04826575).
- Clear high-risk inclusion criteria and clinically meaningful outcomes (PPCs, length of stay).
Limitations
- Non-blinded design may introduce performance bias.
- Detailed physiologic endpoints are truncated in the abstract and may require full-text review for interpretation.
Future Directions: Define optimal components, intensity, and timing of prehabilitation; evaluate cost-effectiveness and scalability across healthcare systems; assess effects on specific complications (e.g., pneumonia, respiratory failure).
BACKGROUND: Respiratory muscle training may improve ventilatory efficiency (V METHODS: We conducted a prospective multicentre, randomised controlled trial (NCT04826575) to examine the effect of prehabilitation in individuals undergoing lung resection. Participants were defined as high-risk for postoperative pulmonary complications if they achieved V RESULTS: A total of 122 patients (46% female; age range: 64-75 yr) completed the study. Postoperative pulmonary complications occurred in 20/58 (34%) of patients randomised to multimodal prehabilitation, compared with 35/64 (55%) patients receiving usual care (odds ratio 2.29 [95% confidence interval 1.10-4.77]; P=0.029). Hospital length of stay was shorter after multimodal rehabilitation compared with patients randomised to receive usual care (from 9 [7-11] days to 7 [6-9] days; P=0.038). After prehabilitation, mean (sd) V CONCLUSIONS: In high-risk patients undergoing elective lung resection surgery, multimodal prehabilitation, including high-intensity respiratory muscle training to target V
2. Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS.
Prospective longitudinal proteomics in ARDS revealed that acute-phase BALF is characterized by heightened humoral immune/B-cell receptor signaling and suppression of HSP90 chaperone and protein-folding pathways, with IFN-γ predicted as an upstream activator and NOTCH1 suppressed. Coagulation and complement activation were more pronounced in the acute than subacute phase in both plasma and BALF.
Impact: This study provides time-resolved, compartment-specific proteomic signatures in ARDS, offering mechanistic insight into immune-chaperone imbalance that may guide biomarker development and targeted interventions.
Clinical Implications: Phase-specific biomarker panels and therapeutic strategies could target acute-phase B-cell signaling and restore chaperone/protein-folding capacity (e.g., HSP90-related pathways) in ARDS.
Key Findings
- Identified 694 plasma and 2017 BALF proteins; coagulation and complement were more pronounced in the acute phase.
- Acute-phase BALF showed activated humoral immunity/B-cell receptor signaling and suppressed HSP90 chaperone cycle and protein-folding pathways.
- Upstream regulator analysis predicted IFN-γ activation and NOTCH1 suppression in acute BALF.
Methodological Strengths
- Prospective, longitudinal sampling of both plasma and BALF across acute and subacute phases.
- Comprehensive mass spectrometry with pathway and upstream regulator analyses (including IPA).
Limitations
- Single-center study with a small ARDS cohort (n=21), limiting generalizability.
- Observational design precludes causal inference; pathway predictions require functional validation.
Future Directions: Validate proteomic signatures in multicentre cohorts; test whether modulating B-cell activity or enhancing HSP90/protein-folding pathways improves ARDS outcomes.
BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a significant clinical challenge, and its pathogenesis is not fully understood. Proteomic analyses of plasma and bronchoalveolar lavage fluid (BALF) in patients with ARDS have been performed to uncover diagnostic and prognostic markers, although previous studies have not adequately focused on longitudinal comparison of biomarkers. This study aimed to elucidate the proteomic profiles of patients with ARDS in the acute and subacute phases to better understand the pathophysiological progression of ARDS. METHODS: This was a single-center, prospective, observational study of adult patients with ARDS in whom plasma and BALF samples were collected in the acute and subacute phases of ARDS and comprehensive proteins were identified and analyzed by mass spectrometry. RESULTS: Plasma and BALF were collected from 21 ARDS patients and plasma from 24 healthy donors, from which 694 plasma proteins and 2017 BALF proteins were analyzed. Processes related to coagulation and complement commonly activated in plasma and BALF were more pronounced in the acute phase than in the subacute phase. In BALF in the acute phase, pathways related to humoral and immune responses were activated, whereas processes related to chaperones and protein folding were suppressed. IPA analysis showed that B cell receptor signaling was most activated, whereas heat shock protein 90 (HSP90) chaperone cycle, protein folding, and other pathways associated with cellular stress responses and proper protein processing were suppressed. The most activated upstream regulator was interferon gamma (IFN-γ) and the most suppressed was notch receptor 1 (NOTCH1). CONCLUSIONS: The proteomics of plasma and BALF from patients with ARDS were compared in both the acute and subacute phases. In BALF in the acute phase, humoral immunity, mainly B-cell receptor signaling, was activated, whereas the HSP90 cycle and protein folding mechanisms were inactivated.
3. Integrating single-cell sequencing and transcriptome analysis to unravel the mechanistic role of sialylation-related genes in sepsis-induced acute respiratory distress syndrome.
Integrative multi-omics identified CD19 and GPR65 as sialylation-related genes with predictive value for sepsis-induced ARDS and implicated CD14 monocytes as key cells. Pathway analyses linked these genes to apoptosis and B-cell receptor signaling, with predicted regulators (NEAT1, OIP5-AS1) and potential drugs (alprostadil, tacrolimus).
Impact: The study advances mechanistic understanding of sepsis-induced ARDS by connecting sialylation biology to specific genes and cell types, generating testable biomarkers and therapeutic hypotheses.
Clinical Implications: CD19 and GPR65, particularly within CD14 monocytes, may serve as biomarkers for risk stratification and as targets for immunomodulation in sepsis-induced ARDS.
Key Findings
- CD19 and GPR65 were identified as sialylation-related key genes with predictive performance via a nomogram model.
- scRNA-seq highlighted CD14 monocytes as key cells; GPR65 expression changed dynamically during their differentiation.
- Regulatory/drug predictions implicated NEAT1, OIP5-AS1, alprostadil, and tacrolimus; CD19 was upregulated in ARDS clinical samples.
Methodological Strengths
- Multi-dataset integration with differential expression, WGCNA, machine learning, and scRNA-seq.
- External validation using clinical samples enhances translational relevance.
Limitations
- Bioinformatic analyses rely on retrospective public datasets and may be affected by batch effects.
- Functional in vivo validation is lacking; clinical sample size and demographics are not detailed.
Future Directions: Prospective validation of CD19/GPR65 as biomarkers, functional studies of sialylation modulation in CD14 monocytes, and early-phase trials of candidate modulators.
BACKGROUND: Studies have shown that sialylation of C1 esterase inhibitors is crucial for their interaction with histones, and histone-C1 esterase inhibitor complexes are detected in acute respiratory distress syndrome (ARDS), suggesting a potential role of sialylation in ARDS. However, the specific function of sialylation in ARDS remains unclear. Therefore, this study aimed to investigate the mechanism of sialylation-related genes (SRGs) in sepsis-induced ARDS. METHODS: The ARDS related datasets (GSE32707, GSE66890, and GSE151263) were included in this study. Candidate genes were identified by implementing differential expression analysis and weighted gene co-expression network analysis (WGCNA). Subsequently, further selection by machine learning and expression assessment confirmed the key genes related to sialylation in sepsis-induced ARDS. Following this, the predictive ability of key genes as a whole for sepsis-induced ARDS was evaluated by creating a nomogram model. Afterwards, enrichment analysis, construction of regulatory networks, and drug prediction analysis were implemented to further understand the molecular mechanisms of action of key genes. Furthermore, single-cell RNA sequencing (scRNA-seq) data analysis was conducted to obtain key cells. Additionally, cell communication and pseudo-time analyses were implemented. In the end, the expression levels of the key genes were assessed by collecting clinical samples. RESULTS: CD19 and GPR65 were identified as key genes associated with sialylation in sepsis-induced ARDS. The constructed nomogram model demonstrated that CD19 and GPR65 as a whole exhibited robust predictive capability for sepsis-induced ARDS. Meanwhile, CD19 and GPR65 were also found to be significantly co-enriched in the apoptosis and B-cell receptor signaling pathway. In addition, some important regulators and drugs with targeting effects on key genes were predicted, such as NEAT1, OIP5-AS1, alprostadil, and tacrolimus. Further, the scRNA-seq data analysis identified nine cell types, among which CD14 monocytes (CD14Mono) was designated as the key cell. Importantly, GPR65 expression exhibited dynamic changes during differentiation of CD14Mono. Also, we found that CD19 was significantly up-regulated in ARDS group. CONCLUSION: We identified CD19 and GPR65 as key genes associated with sialylation in sepsis-induced ARDS, highlighting CD14Mono as key cell type implicated in sepsis-induced ARDS. These findings offered theoretical support for understanding the mechanism of sialylation on sepsis-induced ARDS.