The Role of Cxcr4Hi neutrOPhils in InflueNza

Influenza is still responsible for more than 650,000 deaths per year worldwide and no major improvements in patients' care has been made despite 50 years of research. Most of severe influenza patients suffer from acute lung injury due to a dysregulated immune response. Neutrophils are involved in both host resistance and disease tolerance. Thanks to advances in technologies, the vast variety in neutrophils subpopulations has been revealed. In particular, the subpopulation of CXCR4-expressing neutrophils has been suggested to be involved in the rupture of disease tolerance in lung infections. Nevertheless, these data are from murine models and remain to be confirmed in humans. Moreover, the underlying mechanisms remain unknown as well as the place of primum movens, i.e. vascular or alveolar compartment. The aim of this study is thus to compare the percentage of blood CXCR4-expressing neutrophils between influenza survivors and non-survivors. Percentage of BAL CXCR4-expressing neutrophils will also be compared. To this aim, blood sampling and BAL within the 24 hours and at day 3 after admission to ICU, neutrophils isolation, immunostaining and flow cytometry acquisition will be performed within the 24 hours and at day 3 after admission to ICU. Mortality rate will be collected at Day 28 and Day 90.

Inclusion criteria

• Patient aged 18 yo or above.
• Acute respiratory distress syndrome as defined by the Berlin classification.
• Invasive mechanical ventilation for less than 24 hours.
• Cause of ARDS:

• Influenza infection proven by polymerase chain reaction OR
• Bacterial infection (tracheal aspirate with more than 105 CFU/mL and BAL with more than 104 CFU/mL.
• Pancreatitis according to the 2013 Working Group IAP/APA Acute Pancreatitis Guidelines.
• Peritonitis according to the 2018 SFAR guidelines.
• Health insurance.
• Written informed consent from legal relative or representative.

Exclusion criteria

• Neutropenia (< 500/mm3)
• Neutrophils qualitative defect.
• Patient included in an interventional research assessing an immunomodulatory or antiviral drug.
• Acquired ImmunoDeficiency Syndrome.
• Contraindication to BAL:

• Severe bronshospasm.
• Out-of-control shock.
• Intracranial high pressure.
• Refractory hypoxemia (PaO2/FiO2 < 60 mmHg).
• Legal restriction: prisoners, pregnancy, legal protection.