Innate Immune Response During Community Acquired Pneumonia

NCT03379207 | Terminated

• 1 other identifier: PHAO17/YJ-ImPACT
• Study Type: observational
• Target: 258
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Community-acquired Pneumonia; Acute Respiratory Distress Syndrome; Innate Immunity

Keywords

Community-acquired Pneumonia; Acute Respiratory Distress Syndrome; Innate Immunity; Non Conventional T Lymphocytes

Outcome Measures

Primary Outcomes (4)

• Blood level of Non-Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)

  8 Months

• Airway level of Non-Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)

  8 Months

• Blood level of inflammatory cytokines

  8 months

• Airway level of inflammatory cytokines

  8 months

Secondary Outcomes (6)

• Blood level of Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)

  8 months

• Airway level of Conventional T Lymphocytes (expressed as % CD3+ lymphocytes)

  8 months

• Metabolic signature of non-conventional T lymphocytes

  8 months

• Transcriptomic signature of non-conventional T lymphocytes

  8 Months

• Blood level of Innate Cells (expressed as % CD45+ lymphocytes)

  8 months

Study Arms (2)

"Community Acquired Pneumonia" group

Participants admitted to Intensive Care Unit (ICU) of University Hospital of Tours (France) for Community Acquired Pneumonia. Interventions: * Blood samples for research purpose, taken whenever possible during blood sampling for routine purpose, at inclusion, day 1, 7, and every week during ICU stay Tracheal Aspirates for research purpose: only for mechanically ventilated participants, at inclusion, day 1, 7, and and every week during ICU stay * Surplus of Broncho-alveolar lavage fluid: only if performed for diagnosis purpose by the treating investigator (indication left at his discretion)

Other: Blood samples; Other: Tracheal Aspirates; Other: Surplus of Broncho-alveolar lavage fluid

"Control" group

Participants admitted to Intensive Care Unit of University Hospital of Tours (France) for whom invasive mechanical ventilation is required for an estimated duration of at least 48h, without diagnosis of pneumonia or shock. Interventions: * Blood samples for research purpose, taken whenever possible during blood sampling for routine purpose, at inclusion, day 3, 8, and 15 during ICU stay Tracheal Aspirates for research purpose: at inclusion, day 3, 8, and 15 during invasive mechanical ventilation period, * Surplus of Broncho-alveolar lavage fluid: only if performed for diagnosis purpose by the treating investigator (indication left at his discretion)

Other: Blood samples; Other: Tracheal Aspirates; Other: Surplus of Broncho-alveolar lavage fluid

Interventions

Blood samples OTHER

Blood samples for research purpose, taken whenever possible during blood sampling for routine purpose

"Community Acquired Pneumonia" group; "Control" group

Tracheal Aspirates OTHER

Only for mechanically ventilated participants.

"Community Acquired Pneumonia" group; "Control" group

Surplus of Broncho-alveolar lavage fluid OTHER

Only if performed for diagnosis purpose by the treating investigator : indication left at his discretion

"Community Acquired Pneumonia" group; "Control" group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants admitted to the Intensive Care Unit of the University Hospital of Tours or University Hospital of Limoges (France) with an initial diagnosis of Community Acquired Pneumonia, or participants admitted without diagnosis of pneumonia or shock and for whom invasive mechanical ventilation is required.

You may qualify if:

• "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
• 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

You may not qualify if:

• Participant under protection
• Pregnant or lactating women

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (3)

University Hospitakl of TOURS Département of Pneumonia

Tours, 37044, France

Location

University Hospital -Bretonneau - Intensive Care

Tours, 37044, France

Location

University Hospital of Tours; INSERM CIC 1415

Tours, 37044, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples for all participants; Tracheal aspirations for invasively ventilated patients; Broncho alveolar lavage fluid when available (indication left at the discretion of the investigator)

MeSH Terms

Conditions

Community-Acquired Pneumonia; Respiratory Distress Syndrome

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Youenn JOUAN, MD-PHD

  University of TOURS-INSERM U1100

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2017
• First Posted: December 20, 2017
• Study Start: January 10, 2018
• Primary Completion: June 4, 2025
• Study Completion: June 4, 2025
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

FR (3)