Study on the Correlation Between Alveolar Macrophage-derived Autophagosomes and the Severity of Lung Injury in ARDS

• Conditions: ARDS

• Registration Number: NCT05101694
• Lead Sponsor: Southeast University, China

Brief Summary

In the process of acute respiratory distress syndrome (ARDS), alveolar macrophages can secrete a large number of autophagosomes to mediate the inflammatory response of ARDS and aggravate the pathological damage of the lungs. At the same time, the meta-transcriptome can detect the expression of all genes without a reference genome. This study intends to explore that Whether the alveoli macrophage-derived autophagosomes are related to the severity and prognosis of ARDS, and try to construct a recognition model to predict the prognosis of ARDS.

Detailed Description

Nowadays, acute respiratory distress syndrome (ARDS) is a major clinical problem in the world. Infection and other factors induce immune cells to release inflammatory mediators, and the following uncontrolled inflammatory response is the fundamental reason for the poor prognosis of ARDS. So, it's important to explore the mechanism of ARDS and reduce lung injury.

In the lung tissue, the activation of alveolar macrophages (including alveolar resident macrophages and macrophages recruited in the blood) is an important way that mediates the ARDS inflammatory response. The previous study of the investigator's team proved that alveolar macrophages could not only directly secrete inflammatory mediators, but also mediated the release of inflammatory factors through the secretion of autophagosomes. At the same time, ARDS has been extensively studied in molecular biology, but the prospective exploration of the relationship between the host response and the development mechanism of ARDS is lacking.

The formation of autophagosomes is the marker of autophagy. In the process of ARDS, alveolar macrophages can secrete a large number of autophagosomes to mediate the inflammatory response of ARDS and aggravate the pathological damage of the lungs. At the same time, the meta-transcriptome can detect the expression of all genes without a reference genome, so it has an irreplaceable advantage in exploring the host's response when pathogenic microorganisms invade the body. The investigators speculate that there may be differences in the host response between patients with different types of ARDS.

However, the above results are derived from cell or animal experiments. It hasn't been known whether autophagosomes could be secreted in the alveoli of ARDS patients, and it has not been proven that whether there is a difference in host response between ARDS patients and controls. Therefore, this study intends to explore that Whether the alveoli macrophage-derived autophagosomes are related to the severity and prognosis of ARDS, and try to construct a recognition model to predict the prognosis of ARDS.

Study Timeline

• Study First Submitted: 2021-09-25
• Study First Submitted QC: 2021-10-24
• Study First Posted: 2021-11-01
• Study Start: 2022-01-01
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-17
• Last Update Posted: 2022-07-19
• Primary Completion: 2023-12-30
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Age 18-85 years old
2. Meet ARDS Berlin diagnostic criteria
3. Artificial airway has been established (tracheal intubation, tracheotomy)
4. Sign informed consent
5. Within 7 days of diagnosis of ARDS

Exclusion Criteria

1. Younger than 18 years old or older than 85 years old
2. Pregnant women, cancer and immune system diseases
3. There are contraindications for bronchoscopy (poor oxygenation/severe heart disease, cardiac insufficiency/abnormal blood clotting, massive hemoptysis/aortic aneurysm risk of rupture, etc.)
4. Patients undergoing other clinical trials
5. Estimated survival time <24h

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The link between the proportion of macrophage-derived autophagosomes in alveolar lavage fluid of ARDS patients with the severity of ARDS	at the first day of enrolling the patients	Getting these data through Flow cytometer and analyzing the link between these data with the severity of ARDS
Autophagosomes in alveolar lavage fluid of ARDS patients with the prognosis of ARDS	at the twenty-eighth day of enrolling the patients	Getting these data through Flow cytometer and analyzing the link between these data with the prognosis of ARDS

Secondary Outcome Measures

Name	Time	Method
Mortality	During hospitalization	ICU, 28 day and hospital mortality
Autophagosomes and macrophage-derived autophagosomes in blood	day 1，day 3 or day 7	Getting these data through Flow cytometer and analyzing the link between these data with the prognosis of ARDS
length of stay	During hospitalization	ICU and hospital length of stay
extracellular vesicles	day 1，day 3 or day 7	extracellular vesicles in alveolar lavage fluid and blood through Flow cytometer

Trial Locations

Locations (1)

Nanjing Zhong-Da Hospital, Southeast University; 🇨🇳 Nanjing, Jiangsu, China