Innate Immunity During Community Acquired Pneumonia: A Translational Approach
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 258
- 试验地点
- 3
- 主要终点
- Blood level of Non-Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)
研究概览
简要总结
Community acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Despite recent improvement in acute management (specifically for administration of antibiotics) many severe presentations of pneumonia worsen, progressing to Acute Respiratory Distress Syndrome (ARDS), a clinical entity with 40% hospital mortality.
Dysregulation of immune response is thought to be largely implicated in severe pneumonia progressing to ARDS. Notably, experimental studies have recently suggested the implication of non-conventional T lymphocytes and innate cells in this immunopathology. However, no data are available in Humans in clinical settings.
This study aims to explore the role of non-conventional T cells in pneumonia and ARDS, in participants. For this purpose, 100 participants admitted to Intensive Care Unit (ICU) with a diagnosis of CAP will be included, and 50 "control" participants with no pneumonia nor shock. Presence and functionality of non-conventional T cells and innate cells will be explored using flow-cytometry and ex-vivo stimulation, alongside with cytokines productions. These analyses are conducted in the blood, and, for invasively ventilated participants, in tracheal aspirates or broncho-alveolar fluids if available. For each participants included, the analyses are conducted at different time-points during ICU stay: inclusion, day 3, day 8 and day 15. Moreover, participants with ARDS, for whom a post-ICU follow-up program is normally established after discharge, will have blood analysis from blood samples taken during the follow-up visit up to 8 months after inclusion.
Immunophenotypage and functionality of non-conventional T cells and innate cells will be compared to clinical parameters and their evolution, between "CAP" participants and "Control" participants", and for each participants, according to the different time-point of analysis, in order to better understand dynamic of innate immunity during pneumonia and ARDS.
详细描述
- Clinical and scientific background:
Community acquired pneumonia is a major cause of morbidity and mortality worldwide. Despite recent improvement in acute management (specifically for administration of antibiotics), severe pneumonia can worsen and ultimately progressing to Acute Respiratory Distress Syndrome (ARDS), a clinical entity with an inacceptable 40% hospital mortality. From a pathophysiological point of view, ARDS is characterized by a deregulation of pulmonary inflammation initially triggered by the local aggression, which is, in two-third of the cases, a pneumonia. Alteration of tissue repair is another major characteristic of this entity. So far, the scientific knowledge on this pathophysiology did not translate into specific therapy that could modulate efficiently the inflammatory response and to control the progression from pneumonia to ARDS, and/or to improve tissue repair. Thus, a complete reconsideration of the pathophysiological mechanisms is mandatory. Recent progresses in mucosal biology and innate immunity give interesting new opportunities. Specifically, recently discovered unconventional T cells have shown to be major actors in shaping and modulating early immune responses in the lung mucosa during microbial aggressions and for secondary tissue repair. However, these evidences are limited to pre-clinical models. In many other human diseases (oncology, immune diseases), these sub-populations are already being explored as potential targets for immune therapies.
- Objective of the study:
The aim of this study is to explore potential implications of unconventional T cells during human severe pneumonia and ARDS.
This translational study will complement experimental approaches currently undertaken in the laboratory exploring the role of unconventional T cells in murine models of severe pneumonia and ARDS.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Participant under protection
- •Pregnant or lactating women
结局指标
主要结局
Blood level of Non-Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)
时间窗: 8 Months
Blood level of inflammatory cytokines
时间窗: 8 months
Airway level of inflammatory cytokines
时间窗: 8 months
Airway level of Non-Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)
时间窗: 8 Months
次要结局
- Blood level of Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)(8 months)
- Metabolic signature of non-conventional T lymphocytes(8 months)
- Blood level of Innate Cells (expressed as % CD45+ lymphocytes)(8 months)
- Airway level of Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)(8 months)
- Transcriptomic signature of non-conventional T lymphocytes(8 Months)
- AIrway level of Innate Cells (expressed as % CD45+ lymphocytes)(8 months)