Innate Immunity During Community Acquired Pneumonia: A Translational Approach
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.
⁃ Pneumonia group:
• Admission to the Intensive Care Units or Pneumonia service of Tours University Hospital or Intensive Care Unit or Limoges University Hospital
• Initial diagnosis of acute community-acquired pneumonia suggested by the presence of a cough, dirty sputum, chest pain and / or dyspnea (at least two criteria required), associated with the presence of a radiological or CT infiltrate initially
• Patient for whom it is not envisaged, a priori, to limit treatment within 5 days following inclusion, for ethical reasons, due to age and advanced comorbidities, and / or a level of severity beyond all therapeutic possibilities.
• Diagnosis of pneumonia done within 48 hours after admission to the hospital
• Participant admitted to the hospital for less than 8 days
⁃ Control group:
• Admission to the Intensive Care Units of the University Hospital of Tours or Limoges University Hospital
• Use of invasive mechanical ventilation for less than 48 hours
• Predictable duration of invasive mechanical ventilation\> 48h
• Participant admitted to the hospital for less than 8 days
• Absence of pneumonia criteria (according to the criteria defined for the Pneumonia participant group)
• Absence shock (defined by the need for vasopressor despite volume expansion ≥30mL/kg, associated with a blood lactate level ≥ 2mmol / L
• Patient for whom it is not envisaged, a priori, to limit treatment within 5 days following inclusion, for ethical reasons, due to age and advanced comorbidities, and / or a level of severity beyond all therapeutic possibilities.