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

ARDS Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05101694
• Other study ID #: 2021ZDSYLL215-P01
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: December 30, 2023

Study information

• Verified date: July 2022
• Source: Southeast University, China
• Contact: Dong Xuecheng, bachelor
• Phone: 15850501101
• Email: xuechengdong2020[@]163.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• ARDS
• Lung Injury

Locations

Country	Name	City	State
China	Nanjing Zhong-Da Hospital, Southeast University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Southeast University, China

Country where clinical trial is conducted

China, 

References & Publications (13)

Bel S, Pendse M, Wang Y, Li Y, Ruhn KA, Hassell B, Leal T, Winter SE, Xavier RJ, Hooper LV. Paneth cells secrete lysozyme via secretory autophagy during bacterial infection of the intestine. Science. 2017 Sep 8;357(6355):1047-1052. doi: 10.1126/science.aa — View Citation

Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, — View Citation

Davis S, Wang J, Ferro-Novick S. Crosstalk between the Secretory and Autophagy Pathways Regulates Autophagosome Formation. Dev Cell. 2017 Apr 10;41(1):23-32. doi: 10.1016/j.devcel.2017.03.015. Review. — View Citation

Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. 2018 Jun;19(6):349-364. doi: 10.1038/s41580-018-0003-4. Review. — View Citation

Gonzalez CD, Resnik R, Vaccaro MI. Secretory Autophagy and Its Relevance in Metabolic and Degenerative Disease. Front Endocrinol (Lausanne). 2020 May 5;11:266. doi: 10.3389/fendo.2020.00266. eCollection 2020. Review. — View Citation

Huang X, Xiu H, Zhang S, Zhang G. The Role of Macrophages in the Pathogenesis of ALI/ARDS. Mediators Inflamm. 2018 May 13;2018:1264913. doi: 10.1155/2018/1264913. eCollection 2018. Review. — View Citation

Irish Critical Care Trials Group. Acute lung injury and the acute respiratory distress syndrome in Ireland: a prospective audit of epidemiology and management. Crit Care. 2008;12(1):R30. doi: 10.1186/cc6808. Epub 2008 Feb 29. — View Citation

Liu L, Yang Y, Gao Z, Li M, Mu X, Ma X, Li G, Sun W, Wang X, Gu Q, Zheng R, Zhao H, Ao D, Yu W, Wang Y, Chen K, Yan J, Li J, Cai G, Wang Y, Wang H, Kang Y, Slutsky AS, Liu S, Xie J, Qiu H. Practice of diagnosis and management of acute respiratory distress — View Citation

Mizushima N, Levine B. Autophagy in Human Diseases. N Engl J Med. 2020 Oct 15;383(16):1564-1576. doi: 10.1056/NEJMra2022774. Review. — View Citation

Pourfathi M, Kadlecek SJ, Chatterjee S, Rizi RR. Metabolic Imaging and Biological Assessment: Platforms to Evaluate Acute Lung Injury and Inflammation. Front Physiol. 2020 Aug 31;11:937. doi: 10.3389/fphys.2020.00937. eCollection 2020. Review. — View Citation

Sakr Y, François B, Solé-Violan J, Kotfis K, Jaschinski U, Estella A, Leone M, Jakob SM, Wittebole X, Fontes LE, de Melo Gurgel M, Midega T, Vincent JL, Ranieri VM; SOAP and ICON Investigators. Temporal changes in the epidemiology, management, and outcome — View Citation

Thompson BT, Chambers RC, Liu KD. Acute Respiratory Distress Syndrome. N Engl J Med. 2017 Aug 10;377(6):562-572. doi: 10.1056/NEJMra1608077. Review. — View Citation

Wang J, Davis S, Zhu M, Miller EA, Ferro-Novick S. Autophagosome formation: Where the secretory and autophagy pathways meet. Autophagy. 2017 May 4;13(5):973-974. doi: 10.1080/15548627.2017.1287657. Epub 2017 Feb 15. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The link between the proportion of macrophage-derived autophagosomes in alveolar lavage fluid of ARDS patients with the severity of ARDS	Getting these data through Flow cytometer and analyzing the link between these data with the severity of ARDS	at the first day of enrolling the patients
Primary	Autophagosomes in alveolar lavage fluid of ARDS patients with the prognosis of ARDS	Getting these data through Flow cytometer and analyzing the link between these data with the prognosis of ARDS	at the twenty-eighth day of enrolling the patients
Secondary	Autophagosomes and macrophage-derived autophagosomes in blood	Getting these data through Flow cytometer and analyzing the link between these data with the prognosis of ARDS	day 1,day 3 or day 7
Secondary	extracellular vesicles	extracellular vesicles in alveolar lavage fluid and blood through Flow cytometer	day 1,day 3 or day 7
Secondary	Mortality	ICU, 28 day and hospital mortality	During hospitalization
Secondary	length of stay	ICU and hospital length of stay	During hospitalization