Immune Alveolar Alterations During Pneumonia-Associated Acute Respiratory Distress Syndrome (PICARD2)
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|ClinicalTrials.gov Identifier: NCT03971006|
Recruitment Status : Not yet recruiting
First Posted : June 3, 2019
Last Update Posted : June 3, 2019
Sepsis is a dysregulated host response to severe life-threatening infections, leading to organ failure and death in up to 40% of patients with septic shock. Pulmonary infections are the main cause of community-acquired sepsis and frequently lead to the development of acute respiratory distress syndrome(ARDS). Features of immunosuppression, including diminished cell surface monocyte human leukocyte antigen DR (mHLA-DR) expression, are strongly associated with hospital mortality. Such decrease in HLA-DR expression on antigen-presenting cells has been associated with impairment of microbial antigens to Tcells. Septic patients also show elevated expression of inhibitory receptors associated with cell exhaustion.. Yet, biochemical, flow cytometric and immunohistochemical findings consistent with immunosuppression have been observed in lungs and spleen of patients died of sepsis and multiple organ failure, demonstrating the relevance of studying these defects directly in organ tissues. A novel approach aimed to characterize the role and prognostic value of alveolar biomarkers measured directly in the injured lungs is warranted and supported by: -disappointing results of previous clinical trials attempting to restore the level of biomarkers measured on circulating cells; -evidences of regional immunosuppression in lungs of ARDS patients; -lung is the main site of hospital-acquired infections with a prevalence of ventilator-associated pneumonia in 30% over the course of Intensive Care Unit(ICU) stay in ARDS patients.
Investigators speculate that biomarkers measured on alveolar leukocytes (AL) surface, are important predictors of outcome and potential therapeutic targets in ICU patients with pneumonia-associated ARDS.
Investigators aim to explore whether biomarkers measured directly on AL from patients with pneumonia-associated ARDS are associated to regional pulmonary immunosuppression using leukocyte functional tests; and predictors of outcomes.
Bronchoalveolar lavage fluid(BALF) and blood samples will be collected in ARDS patients. Leukocyte populations and cell membrane biomarkers will be quantified using flow cytometry. Leukocyte functional tests will be performed ex vivo on leukocytes collected from BALF and blood samples. Pharmacological interventions will be performed ex vivo.
This project aims to identify biomarkers associated with outcomes and potential therapeutic targets.
|Condition or disease|
|Acute Respiratory Distress Syndrome|
|Study Type :||Observational|
|Estimated Enrollment :||110 participants|
|Official Title:||Immune Alveolar Alterations During Pneumonia-Associated Acute Respiratory Distress Syndrome|
|Estimated Study Start Date :||June 1, 2019|
|Estimated Primary Completion Date :||June 4, 2022|
|Estimated Study Completion Date :||June 28, 2022|
Immunocompetent ARDS patients
(n=50) Patients with moderate-to-severe pneumonia-associated Acute Respiratory Distress Syndorme (ARDS) and no immunosuppression (excluding patients with HIV infection, solid tumor or hematological malignancies, organ transplant or taking steroids since more than 4 weeks).
Immunosuppressed ARDS patients
(n=50) Patients with moderate-to-severe pneumonia-associated Acute Respiratory Distress Syndorme (ARDS) (Berlin definition (2)) and previously known immunosuppression (as listed above). These patients will allow comparing the cell defects observed in the study population to those observed in immunosuppressed patients.
(n=10) Patients undergoing a bronchoscopy with Bronchoalveolar Liquid (BAL) as part of routine care but having neither ARDS nor active lung infection, infiltrating lung disease or immunosuppression. These patients will allow quantifying normal levels of the studied biomarkers in the alveolar and blood compartments.
- HLA-DR expression level of alveolar monocytes at the early phase of infectious Acute Respiratory Distress Syndrome (ARDS) [ Time Frame: at day 1 to day 3 ]Measurement by flow cytometry phagocytosis and TNF-α synthesis of alveolar monocytes in immunocompetent patients, compared to immunocompromised patients
- Impact of the level of expression of PD-1 by alveolar CD8 + lymphocytes on their function during septic ARDS in immunocompetent and immunocompromised patients. [ Time Frame: at day 1 to day 3 ]Level of expression of PD-1 by alveolar CD8+ lymphocytes
- Comparaison of the level of HLA-DR expression of alveolar monocytes between immunocompetent and immunosuppressed patients being managed for septic ARDS. [ Time Frame: at day 1 to day 3 ]Level of HLA-DR expression of alveolar monocytes
- Link between the alveolar monocyte HLA-DR expression level and the prognosis of immunocompetent and immunosuppressed patients being managed for septic ARDS. [ Time Frame: day 28 ]Number of days without complication
- Determine wether alveolar biomarkers (HLA-DR and PD-1) are potential candidates for immunomodulation [ Time Frame: at day 1 to day 3 ]To determine if the level of expression of HLA-DR and PD-1 can be modulated by pharmacological intervention
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03971006
|Contact: Nicolas DE PROST, Doctor||01 49 81 23 94 ext email@example.com|
|Principal Investigator:||Nicolas DE PROST||Assistance Publique Hôpitaux de Paris - CHU Henri Mondor - Créteil|