Acute respiratory distress syndrome (ARDS) is a serious lung condition in which fluid builds up in the air sacs, making it hard to breathe and often requiring intensive care. Older adults fare worse because their lung-lining cells lose the ability to heal properly after injury This study will explore two key molecules-RSPO3 and Syndecan-1 (SDC-1)-that normally help alveolar (air-sac) cells regenerate. We will collect small blood samples from ARDS patients and, when patients undergo elective lung surgery, tiny pieces of healthy lung tissue. In the lab, we will also grow three-dimensional "lung organoids" from these samples to see how boosting or blocking RSPO3/SDC-1 affects cell repair
Our goals are to:
Measure RSPO3/SDC-1 activity alongside inflammatory markers (e.g., IL-6, TNF-α) to understand their roles in age-related repair failure.
Build an integrated platform for early diagnosis, disease monitoring, and treatment evaluation in older ARDS patients.
Identify molecular targets that could lead to new therapies, helping older adults recover lung function more effectively.
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ARDS Group: 500 adult patients with acute respiratory distress syndrome, enrolled across five age brackets (20-30, 30-40, 50-60, 70-80, and \> 80 years), with 100 participants per stratum Lung Resection Control Group: 500 patients undergoing elective lobectomy for non-infectious pulmonary conditions (e.g., lung tumors, interstitial lung disease), matched by age bracket and size to the ARDS cohort
Other
Prospective
RSPO3/SDC-1 pathway profiling assay
Procedure/SurgeryPeripheral Blood: 5 mL collected into EDTA tubes; PBMCs isolated within 2 h for RT-qPCR analysis of RSPO3/SDC-1 mRNA and sandwich ELISA quantification of protein levels. Saliva: 2-3 mL unstimulated saliva naturally expectorated into sterile tubes, kept at 4 °C and processed within 2 h (centrifuged, aliquoted) before -80 °C storage Subcutaneous Fat: 100-200 mg obtained during elective procedures, preserved in RNAlater at 4 °C for 24 h, then frozen at -80 °C 3D Alveolar Organoid Assay: Lung tissue-derived organoids are cultured in Matrigel and treated ex vivo with recombinant RSPO3 or SDC-1 neutralizing antibody; epithelial repair is assessed over 7 days by Ki-67 immunostaining and wound-closure measurement
Blood and Saliva
Procedure/SurgeryPeripheral Blood: 5 mL collected into EDTA tubes; PBMCs isolated within 2 h for RT-qPCR analysis of RSPO3/SDC-1 mRNA and sandwich ELISA quantification of protein levels. Saliva: 2-3 mL unstimulated saliva naturally expectorated into sterile tubes, kept at 4 °C and processed within 2 h (centrifuged, aliquoted) before -80 °C storage
Correlation Between Peripheral Blood RSPO3/SDC-1 Pathway Activity and Alveolar Epithelial Injury Marker Levels
Quantify RSPO3 and Syndecan-1 expression in peripheral blood (by RT-qPCR and ELISA) and measure alveolar injury biomarkers (SP-A, SP-D) in serum. Calculate Pearson or Spearman correlation coefficients between RSPO3/SDC-1 levels and SP-A/SP-D concentrations in elderly ARDS patients at baseline.
Effect of RSPO3/SDC-1 Pathway Modulation on Alveolar Organoid Repair Capacity
Assess lung organoid epithelial repair by measuring (1) percentage of Ki-67-positive cells and (2) wound-closure area in 3D alveolar organoid cultures treated with recombinant RSPO3 protein or SDC-1 neutralizing antibody versus untreated controls.
Diagnostic Performance of the RSPO3/SDC-1-Based Integrated Platform
Evaluate the multi-marker platform combining RSPO3/SDC-1 activity and inflammatory cytokines (IL-6, TNF-α) by calculating AUC, sensitivity, specificity, PPV, and NPV for predicting impaired alveolar repair in elderly ARDS patients.
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