Study of the Effects of Bronchoalveolar Lavage Liquid in the ARDS on the Functioning of the Neutrophil Polynuclear System
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Lifespan of the PNNs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 接受健康志愿者
- 否
入选标准
- •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%.
排除标准
- •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.
结局指标
主要结局
Lifespan of the PNNs
时间窗: 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)
次要结局
- PNNs phagocytic index(24 hours after BAL)
- Efferocytosis index(24 hours after BAL)
- Increase of PNNs phagocytic index with HMGB1 activator(24 hours after BAL)
- Increase of Efferocytosis index metformin(24 hours after BAL)