The Role of Cxcr4Hi neutrOPhils in InflueNza (CHOPIN)

The Role of CXCR4-expressing Neutrophils in Influenza-related Acute Respiratory Distress Syndrome

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. Especially, there is no therapeutic strategy targeting the dysregulated host response. CXCR4-expressing neutrophils seem to be involved in the rupture of host resistance. The aim of this study is thus to compare the percentage of blood CXCR4-expressing neutrophils between influenza survivors and non-survivors.

Study Overview

• Status: Recruiting
• Conditions: Influenza; Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: Additional tubes and LBA

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Renaud PREVEL, Dr; Phone Number: +33 5 57 87 26 26; Email: renaud.prevel@u-bordeaux.fr

Study Locations

• France
  • Bordeaux, France, 33000
    • Recruiting
    • Hôpital Pellegrin
    • Contact: Renaud PREVEL, Dr; Phone Number: +33 5 57 87 26 26; Email: renaud.prevel@u-bordeaux.fr
  • Pessac, France, 33604
    • Not yet recruiting
    • Hôpital Haut-Lévêque
    • Contact: Antoine DEWITTE, Dr; Email: antoine.dewitte@u-bordeaux.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The population of interest will be patients with acute respiratory distress syndrome according to the Berlin criteria.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Influenza-related ARDS group; Person with influenza virus infection proven by a positive polymerase chain reaction test for the influenza ARDS group. Additional tubes taken when blood is drawn during treatment, and bronchoalveolar fluid sample.	Other: Additional tubes and LBA; 4 Additional tubes taken when blood is drawn during treatment : EDTA tubes and 2 citrate tubes and bronchoalveolar fluid sample (LBA)
Bacterial-related ARDS group; A person with a proven bacterial infection (105 colony-forming units/mL for tracheal aspirates and more than 104 colony-forming units/mL for BAL). Additional tubes taken when blood is drawn during treatment, and bronchoalveolar fluid sample.	Other: Additional tubes and LBA; 4 Additional tubes taken when blood is drawn during treatment : EDTA tubes and 2 citrate tubes and bronchoalveolar fluid sample (LBA)
Extra-pulmonary (digestive inflammation) ARDS group; Person presenting with acute pancreatitis according to the 2013 international recommendations (typical pain, lipasemia above 3 times normal and/or abnormality on imaging). Or Person presenting with acute bacterial peritonitis based on a clinical diagnosis and bacteria isolated on peritoneal samples (RFE SFAR 2018). Additional tubes taken when blood is drawn during treatment, and bronchoalveolar fluid sample.	Other: Additional tubes and LBA; 4 Additional tubes taken when blood is drawn during treatment : EDTA tubes and 2 citrate tubes and bronchoalveolar fluid sample (LBA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biological	Percentage of blood CXCR4-expressing neutrophils within the 24 hours following admission to ICU for invasive mechanical ventilation.	Day 1 after inclusion
Clinical	Mortality	Day 28 after inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Study Chair: Edouard LHOMME, Dr, Unité de Soutien Méthodologique à la Recherche clinique et épidémiologique du CHU de Bordeaux

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: neutrophils; CXCR4; disease tolerance; host resistance
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Disease; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Influenza, Human; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: CHUBX 2023/41

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No