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出境医 / 临床实验 / Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System (BALARDS)

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

Study Description
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.


Condition or disease Intervention/treatment
ARDS, Human Procedure: Bronchoalveolar lavage

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.

Study Design
Layout table for study information
Study Type : Observational
Actual Enrollment : 42 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System
Actual Study Start Date : May 5, 2015
Actual Primary Completion Date : May 5, 2016
Actual Study Completion Date : May 5, 2016
Arms and Interventions
Group/Cohort Intervention/treatment
ARDS group
Inpatients hospitalized in medical intensive care with a table of ARDS defined according to the Berlin criteria and requiring an BAL for a diagnostic purpose under a suspicion of pneumopathy acquired under mechanical ventilation.
Procedure: Bronchoalveolar lavage
Control group
The control group will be made up of patients with an 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%.
Procedure: Bronchoalveolar lavage
Outcome Measures
Primary Outcome Measures :
  1. Lifespan of the PNNs [ Time Frame: 24 hours after BAL ]

    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)



Secondary Outcome Measures :
  1. PNNs phagocytic index [ Time Frame: 24 hours after BAL ]

    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).


  2. Efferocytosis index [ Time Frame: 24 hours after BAL ]
    The efferocytosis index was determined on 300 cells as the percentage of Human monocyte-derived macrophages (HMDMs) containing at least one ingested apoptotic neutrophil.

  3. Increase of PNNs phagocytic index with HMGB1 activator [ Time Frame: 24 hours after BAL ]
    PNNs phagocytic index is measured after incubation with an anti-HMGB1 neutralising antibody

  4. Increase of Efferocytosis index metformin [ Time Frame: 24 hours after BAL ]
    efferocytosis index was determined after incubation with an AMP-activated protein kinase (AMPK) activator (metformin)


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
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%.
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.
Contacts and Locations

Locations
Layout table for location information
France
CHU de Rennes
Rennes, France, 35033
Sponsors and Collaborators
Rennes University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Jean-Marc TADIE, MD, PhD University Hospital of Rennes
Tracking Information
First Submitted Date July 2, 2019
First Posted Date July 5, 2019
Last Update Posted Date July 8, 2019
Actual Study Start Date May 5, 2015
Actual Primary Completion Date May 5, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 2, 2019)
Lifespan of the PNNs [ Time Frame: 24 hours after BAL ]
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)
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: July 2, 2019)
  • PNNs phagocytic index [ Time Frame: 24 hours after BAL ]
    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).
  • Efferocytosis index [ Time Frame: 24 hours after BAL ]
    The efferocytosis index was determined on 300 cells as the percentage of Human monocyte-derived macrophages (HMDMs) containing at least one ingested apoptotic neutrophil.
  • Increase of PNNs phagocytic index with HMGB1 activator [ Time Frame: 24 hours after BAL ]
    PNNs phagocytic index is measured after incubation with an anti-HMGB1 neutralising antibody
  • Increase of Efferocytosis index metformin [ Time Frame: 24 hours after BAL ]
    efferocytosis index was determined after incubation with an AMP-activated protein kinase (AMPK) activator (metformin)
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 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
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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%.
Condition ARDS, Human
Intervention Procedure: Bronchoalveolar lavage
Study Groups/Cohorts
  • ARDS group
    Inpatients hospitalized in medical intensive care with a table of ARDS defined according to the Berlin criteria and requiring an BAL for a diagnostic purpose under a suspicion of pneumopathy acquired under mechanical ventilation.
    Intervention: Procedure: Bronchoalveolar lavage
  • Control group
    The control group will be made up of patients with an 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%.
    Intervention: Procedure: Bronchoalveolar lavage
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 2, 2019)
42
Original Actual Enrollment Same as current
Actual Study Completion Date May 5, 2016
Actual Primary Completion Date May 5, 2016   (Final data collection date for primary outcome measure)
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.
Sex/Gender Not Provided
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers Not Provided
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT04008225
Other Study ID Numbers 35RC15_9885
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Rennes University Hospital
Study Sponsor Rennes University Hospital
Collaborators Not Provided
Investigators
Principal Investigator: Jean-Marc TADIE, MD, PhD University Hospital of Rennes
PRS Account Rennes University Hospital
Verification Date July 2019