The Role and Mechanism of O-GlcNAc Glycosylation Modified HAS2 in the Hyaluronic Acid Synthesis in ARDS

Study Overview
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Brief Summary
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Maintaining the normal function of the pulmonary microvascular barrier is critical for ARDS treatment. To assess the relationship between the HAS2 protein level, HA content and the clinical prognosis of ARDS in patients with ARDS. Compare the HAS2 protein levels, HMW-HA and LMW-HA levels, endothelial injury indicators, and lungs in the blood of severe and non-ARDS severe patients and healthy adults admitted to the ICU. The correlation between permeability, disease severity and prognosis to explore the predictability of HAS2-HA on the clinical outcome of ARDS.

Official Title
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The Role and Mechanism of O-GlcNAc Glycosylation Modified HAS2 in the Hyaluronic Acid Synthesis in ARDS

Conditions
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Hyaluronic Acid

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.85 years≥Age≥18 years. 2.Moderate-to-severe ARDS, defined by the ARDS Definition Task Force in the Berlin definition (partial pressure of arterial oxygen [PaO2]:FiO2 ratio ≤200 mmHg with a PEEP ≥5 cmH2O). 3.Diagnosis of ARDS less than 72 hours. Exclusion Criteria: All patients who meet any of the following criteria will be excluded at enrollment and randomization. Severe chronic respiratory diseases requiring long-term home oxygen therapy or noninvasive MV. Undrained pneumothorax or subcutaneous emphysema. Severe neuromuscular disease. Hemodynamic instability (>30% increase in vasopressors within 6 hours or norepinephrine >0.5 ug/kg/min) (Am J Respir Crit Care Med. 2020; 201(2):178-187) . Contraindications to hypercapnia, such as intracranial hypertension or acute coronary syndrome. Severe other organs dysfunction with a low expected survival (7 days) or palliative care. Solid organ or hematologic tumors with the expected survival time less than 30 days. Participating in other clinical trials within 30 days. Pregnancy. Refusal to sign the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ARDS group<br>1.85 years≥Age≥18 years. 2.Moderate-to-severe ARDS, defined by the ARDS Definition Task Force in the Berlin definition (partial pressure of arterial oxygen [PaO2]:FiO2 ratio ≤200 mmHg with a PEEP ≥5 cmH2O). 3.Diagnosis of ARDS less than 72 hours. 4.Just observation | |
| Critically ill patients without ARDS group<br>Unstable vital signs, rapid changes in the condition, unstable function of more than two organ systems (excluding the respiratory system), decline or failure, the development of the disease may endanger the life of the patient. | |
| healthy adult group<br>Healthy adults, voluntarily join the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day fatality Rate | 28-day mortality (patients will be followed for 28 days) | 28 days after enrollment | 
| 90-day fatality rate | 90-day mortality (patients will be followed for 90 days) | 90 days after enrollment | 
| ICU hospital stay | Length of ICU stay | through study completion, an average of 4 week | 
| ICU fatality rate | The ratio of the total number of deaths from all causes of the enrolled patients during ICU hospitalization. | through study completion, an average of 4 week | 
| Wearing time from mechanical ventilation | successful weaning defined as the absence of the requirement for ventilatory support, without reintubation | through study completion，an average of 4 week | 
| Peripheral blood HMW-HA and LMW-HA levels | ELISA method to separate and detect HMW-HA and LMW-HA levels（Units of Measure unit nM/ml） | 0, 1, 3, 7 days after enrollment | 
| HAS2 protein content in peripheral blood | ELISA method detects HAS2 protein in peripheral blood | 0, 1, 3, 7 days after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ENOS, ET-1, vWF levels in peripheral blood | ELISA method to detect eNOS, ET-1, vWF in peripheral blood to evaluate endothelial cell damage（Measure unit ng/ml） | 0, 1, 3, 7 days after enrollment | 
| Levels of bound mucinoglycans-1, nitric oxide, and acetylheparin sulfate in peripheral blood | glycocalyx levels of the endothelium were assessed by measuring the levels of mucin polysaccharide-1, nitric oxide and acetyl heparan sulfate in peripheral blood by ELISA assay（Measure unit ng/ml） | 0, 1, 3, 7 days after enrollment | 
| In peripheral blood, IL-1α, IL-6, neutrophils, lymphocytes, descending Procalcin, C-reactive protein value | The ELISA method detects IL-1α and IL-6 in the blood, and records the blood neutrophils, lymphocytes, and vary in procalcin and C-reactive protein to assess the inflammatory response of ARDS(Measure unit pg/ml） | 0, 1, 3, 7 days after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyaluronic acid synthase 2, Acute respiratory distress syndrome, Pulmonary microvascular endothelial barrier;, Hyaluronic acid