Mechanism of Delayed Neutrophil Apoptosis in Acute Lung Injury

NCT04607434 | Completed DMC

• 1 other identifier: jdyyicu3
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Literature basis Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by respiratory distress and progressive hypoxemia, which is caused by diffuse alveolar and pulmonary interstitial edema caused by various pulmonary and extrapulmonary factors other than cardiogenic factors. ARDS incidence rate is as high as 75 /10 000 per year, and sepsis and pulmonary infection are the most common causes. In the past, it was generally believed that excessive immune activation is the core of the pathophysiology of ARDS, and neutrophils are recognized as the core driver of inflammatory hyperactivity and lung injury in ARDS. Although some progress has been made in the epidemiology, pathogenesis and pathophysiology of ARDS in the past 50 years, and the clinical outcomes of some patients with ARDS have been improved by optimizing the mode of mechanical ventilation and fluid treatment, as well as prone ventilation and the use of muscle relaxants, ARDS is still one of the most common causes of death and disability in intensive care units, The mortality rate of the disease is currently as high as 30-40%. There is still a lack of effective drugs for the treatment of ARDS in clinic, and even glucocorticoids applied for immune overactivation have not achieved good results. This is related to the unclear pathogenesis of ARDS. Therefore, it is still a hot and difficult point to further explore the pathogenesis and progression of ARDS and find new therapeutic targets. In the past, mature PMN in peripheral blood was generally considered as a functional cell in the end stage, but it is widely involved in different innate immune responses (including inflammation, infection, tumor, autoimmunity, etc.) and can adopt very different effector mechanisms. Therefore, with the deepening of research, neutrophil subtypes with different functions (such as immune regulation and repair) have been identified in recent years: cd16dimcd62lbrightpmn and cd16brightcd62ldimmpmn. In the steady state of healthy people, the classic mature neutrophils (cd16brightcd62lbright) in peripheral blood account for more than 98% of the total PMN, and the proportion of the two neutrophil subtypes is relatively low. In the inflammatory state, the proportion of cd16dimcd62lbright and cd16brightcd62ldim neutrophils increased significantly. Proteomic analysis showed that there were significant differences between the two subtypes of neutrophils. The nucleus of cd16dimcd62lbright neutrophil subgroup is banded, which is released from bone marrow after being stimulated by lipopolysaccharide (LPS). It accounts for 20% - 25% of PMN in whole blood in LPS infection model. The apoptosis rate is significantly reduced, and the bacteriostatic effects such as oxidative burst and phagocytosis are significantly enhanced; On the contrary, cd16brightcd62ldim neutrophil subgroup has reduced antibacterial ability and shows immunosuppressive phenotype. It is a newly discovered neutrophil subtype with immunosuppressive function in recent years, which can inhibit T cell proliferation, which is related to immunosuppression in the experimental human endotoxemia model. In our previous studies, we have successfully obtained a new amino acid derivative of ocotillol ginsenoside, which may have the pharmacological activities of ocotillol ginsenoside and glycine, and has a potential role in improving the delay of apoptosis and immunosuppression of ARDS neutrophil subtypes, and has the potential of new drug development for the treatment of ARDS. The experimental steps are as follows: Firstly, the peripheral blood of ARDS patients in ICU was collected, and neutrophils were isolated from the peripheral blood. The proportion of neutrophil subtypes and the degree of apoptosis were detected by flow cytometry. Co culture with human T lymphocytes in vitro to observe its ability to inhibit T cell proliferation. Then, the neutrophils of ARDS patients were cultured with different doses of ginsenoside glycine derivatives, and the detection of the above indexes was repeated again. Finally, the mechanism of neutrophils in the pathogenesis and progression of ARDS was discussed.

Conditions

Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); Neutrophils; Apoptosis; Immunosuppression; Pathogenesis

Outcome Measures

Primary Outcomes (1)

• Inpatient mortality rate

  Inpatient mortality during ICU stay in the enrolled patients

  Within 28 days

Secondary Outcomes (2)

• New infection rate

  5 days after check-in at ICU

• the apoptosis rate

  20 hours

Interventions

Ocotillol Type Ginsenoside Derivatives DRUG

Peripheral blood PMN of patients with ARDS were taken. The neutrophils isolated from peripheral blood of ARDS patients were incubated with different doses of OCT glycine derivatives (20,50,100 UM) for 20 h

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

ICU patients admitted to the first hospital of Jilin University in Changchun City, Jilin Province, China

You may qualify if:

• ≥age ≥ 18 years old
• patients in ICU; within 24 hours of diagnosis of acute lung injury (Berlin criteria for acute lung injury)

You may not qualify if:

• death within 48 hours of admission
• Pregnancy or puerperium
• Patients with immunosuppression

Sponsors & Collaborators

• The First Hospital of Jilin University: lead

Study Sites (1)

first hospital of Jilin University

Changchun, 130021, China

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

The peripheral blood of the patient was centrifuged and the supernatant was reserved for cryopreservation

MeSH Terms

Conditions

Acute Lung Injury; Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• jing zhang, doctor

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of critical care medicine center

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: October 29, 2020
• Study Start: January 1, 2021
• Primary Completion: December 31, 2021
• Study Completion: February 1, 2022
• Last Updated: September 13, 2023

Record last verified: 2023-09

Locations

CN (1)