Clinical trial NCT05101694: Study on the Correlation Between Alveolar Macrophage-derived Autophagosomes and the Severity of Lung Injury in ARDS
Official title: Study on the Correlation Between Alveolar Macrophage-derived Autophagosomes and the Severity of Lung Injury in ARDS
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: ARDS
Keywords: macrophage
autophagosome
gene
Lead sponsor: Southeast University, China
Sponsor class: OTHER
First posted: 2021-11-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients diagnosed with ARDS in the Department of Critical Care Medicine, Zhongda Hospital, Southeast University from October 2021 to May 2022

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.

Eligibility criteria: 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

Primary outcomes:
measure: The link between the proportion of macrophage-derived autophagosomes in alveolar lavage fluid of ARDS patients with the severity of ARDS
timeFrame: at the first day of enrolling the patients
measure: Autophagosomes in alveolar lavage fluid of ARDS patients with the prognosis of ARDS
timeFrame: at the twenty-eighth day of enrolling the patients
Secondary outcomes:
measure: Autophagosomes and macrophage-derived autophagosomes in blood
timeFrame: day 1，day 3 or day 7
measure: extracellular vesicles
timeFrame: day 1，day 3 or day 7
measure: Mortality
timeFrame: During hospitalization
measure: length of stay
timeFrame: During hospitalization
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Zhong-Da Hospital, Southeast University
state: Jiangsu
Study officials:
affiliation: Southeast University
name: Ling Liu, Dr
role: STUDY_DIRECTOR
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