Clinical trial NCT04008225: Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System
Official title: Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ARDS, Human
Keywords: Bronchoalveolar lavage
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 42
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * ARDS Group : Inpatients hospitalized in medical intensive care with an ARDS defined according to the Berlin criteria and requiring an BAL(for diagnostic purpose in suspicion of pneumopathy acquired under mechanical ventilation).
* Control group : The control population is made up with patients with a BAL considered normal (endoscopy patients from the pneumology department). The normality of the BAL is defined by a normocellular wash with cellularity: \< 150,000 to 200,000 cells/mL Cell composition (formula): macrophages: 80-90%, lymphocytes 5 to 10% (\< 20%), neutrophils: \< 5%, eosinophils: \< 2%.

Brief summary: Firstly, the study assesses the effect of bronchoalveolar lavage fluid (BAL) from patients in (acute respiratory distress syndrome (ARDS) on the life span of PNNs and on the phagocytosis of apoptotic cells by macrophages and polynuclear neutrophil (PNN).

Then, the effect of an antibody directed against "high-mobility group box 1" protein (HMGB1) and the effect of metformin on efferocytosis are studied.

Detailed description: ARDS (acute respiratory distress syndrome) is a syndrome that causes significant mortality and morbidity. This syndrome is characterized by an alveolitis with polynuclear neutrophil (PNN). PNNs play an important role in the persistence and in injuries induced by ARDS. Several animal studies have shown that lesional edema can be increased by two important mechanisms: the increase in the lifespan of PNNs in the lung and the decrease in the phagocytosis capacities of apoptotic cells (efferocytosis) by macrophages and PNNs.

However, confirmation of these data in humans does not exist, and knowledge of the mechanisms that may increase lung damage during ARDS will limit it and thus reduce the mechanical ventilation time of these patients as well as the mortality associated with ARDS.

" high-mobility group box 1 " (HMGB1) protein may be involved in reducing efferocytosis capacity. Similarly, activation of AMP-activated protein kinase (AMPk) could restore the clearance capacity of apoptotic cells in macrophages and PNNs.

Eligibility criteria: Inclusion Criteria:

* ARDS Group : Inpatients hospitalized in medical intensive care with an ARDS defined according to the Berlin criteria and requiring an BAL(for diagnostic purpose in suspicion of pneumopathy acquired under mechanical ventilation).
* Control group : The control population is made up with patients with a BAL considered normal (endoscopy patients from the pneumology department). The normality of the BAL is defined by a normocellular wash with cellularity: \< 150,000 to 200,000 cells/mL Cell composition (formula): macrophages: 80-90%, lymphocytes 5 to 10% (\< 20%), neutrophils: \< 5%, eosinophils: \< 2%.

Exclusion Criteria:

* Age \< 18 years;
* Pregnant women ;
* Persons deprived of their liberty by judicial or administrative decision;
* Persons legally incapable;
* Persons not affiliated to a social security system;
* Previously immunocompromised patients (HIV infection, hematopathy, organ transplantation, immunosuppression);
* Patients who do not require a lung sample.

Primary outcomes:
measure: Lifespan of the PNNs
timeFrame: 24 hours after BAL
Secondary outcomes:
measure: PNNs phagocytic index
timeFrame: 24 hours after BAL
measure: Efferocytosis index
timeFrame: 24 hours after BAL
measure: Increase of PNNs phagocytic index with HMGB1 activator
timeFrame: 24 hours after BAL
measure: Increase of Efferocytosis index metformin
timeFrame: 24 hours after BAL
Other outcomes:
Locations:
city: Rennes
country: France
facility: CHU de Rennes
Study officials:
affiliation: University Hospital of Rennes
name: Jean-Marc TADIE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: