Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System

ARDS, Human Clinical Trial

— BALARDS  

Official title:

Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04008225
• Other study ID #: 35RC15_9885
• Status: Completed
• Start date: May 5, 2015
• Est. completion date: May 5, 2016

Study information

• Verified date: July 2019
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 5, 2016
• Est. primary completion date: May 5, 2016
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• ARDS, Human
• Respiratory Distress Syndrome, Adult

Intervention

Procedure:
• Bronchoalveolar lavage

Locations

Country	Name	City	State
France	CHU de Rennes	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lifespan of the PNNs	The lifespan of the PNNs is an indicator of apoptosis : two groups are compared with and without incubation in BAL fluid.; Neutrophil necrosis was assessed by flow cytometry using a phycoerythrin-conjugated active caspase-3 apoptosis kit (Becton Dickinson, USA)	24 hours after BAL
Secondary	PNNs phagocytic index	This index relates the ability of the PNNs to produce neutrophil extracellular traps (NETs).; The release of NETs was quantified by measuring fluorescence with a microplate fluorescence reader (Varioskan, ThermoFisher Scientific, USA).	24 hours after BAL
Secondary	Efferocytosis index	The efferocytosis index was determined on 300 cells as the percentage of Human monocyte-derived macrophages (HMDMs) containing at least one ingested apoptotic neutrophil.	24 hours after BAL
Secondary	Increase of PNNs phagocytic index with HMGB1 activator	PNNs phagocytic index is measured after incubation with an anti-HMGB1 neutralising antibody	24 hours after BAL
Secondary	Increase of Efferocytosis index metformin	efferocytosis index was determined after incubation with an AMP-activated protein kinase (AMPK) activator (metformin)	24 hours after BAL