Study of the Immunological Pathophysiological Mechanisms Associated With Acute Respiratory Distress Syndrome (IMMUNORESP2)

About 10% of patients admitted to the ICU suffer from ARDS, with a mortality rate of around 35-45%. The lack of therapeutic innovation in ARDS can be partly explained by the heterogeneity of patients included under this definition.

A better understanding of the pathophysiological mechanisms underlying the different patient phenotypes is essential to develop new therapeutic strategies.

Objectives:

To characterize the inflammatory profile of patients with ARDS using circulating biomarkers and single-cell RNA sequencing of pulmonary immune cells.

The investigators hypothesize that there is a correlation between the profile of serum biomarkers (inflammatory sub-phenotypes), the transcriptome of pulmonary immune cells.

Briefly the experimental scheme is as follow:

• Population: patients with ARDS under invasive mechanical ventilation in the ICU.

• Intervention:

  1. Determination of the inflammatory subphenotype on circulatory inflammatory biomarkers.
  2. Characterization of inflammation by single cell RNA sequencing on lung immune cells collected on broncho-alveolar fluid.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome (ARDS)

Detailed Description

Acute Respiratory Distress Syndrome (ARDS) is the most severe form of pulmonary failure. It is defined by bilateral radiologic opacities associated with severe hypoxemia, confirmed by a PaO₂/FiO₂ ratio <300 in the absence of a cardiac cause. About 10% of patients admitted to the Intensive Care Units (ICU) develop ARDS, and this diagnosis is associated with an in-hospital mortality of 35-45%. Like sepsis, ARDS leads to long-term complications. It is associated with physical deconditioning and reduced quality of life that can persist up to five years after the episode. Survivors are readmitted to the ICU within a year in 30% of cases. Moreover, excess mortality among ARDS survivors is attributable, in nearly one-third of cases, to a new acute respiratory infection.

The lack of therapeutic advances in ARDS has led researchers to better characterize patients with this condition. Different subphenotypes have been identified based on plasma inflammatory biomarker profiles, which are associated with distinct responses to treatments (such as corticosteroids, ventilatory management, and fluid management) and variable prognoses. The mechanisms underlying these different biological subphenotypes remain unknown. To further explore this concept, it is necessary to precisely identify subpopulations of patients who present with similar clinical features but distinct biological phenotypes driven by unique pathophysiological mechanisms. Establishing these different ARDS endotypes is essential for the development of innovative and targeted therapeutic strategies.

Our hypothesis is that the different biological subphenotypes of ARDS reflect distinct profiles of pulmonary immune cell populations, representing a first step toward understanding ARDS endotypes.

Identifying these endotypes is a crucial step for developing targeted and innovative therapeutic strategies aimed at reducing ARDS-related morbidity and mortality. This is the objective of the proposed project.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Benjamin Chousterman, MD PhD; Phone Number: +330149958518; Email: benjamin.chousterman@aphp.fr
• Study Contact Backup: Name: Pierre-Louis BLOT, MD; Phone Number: +331049956565; Email: pierre-louis.blot@aphp.fr

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Hopital Lariboisiere
    • Contact: Pierre-Louis BLOT, MD; Phone Number: +33 01 49 95 85 15; Email: pierre-louis-blot@aphp.fr
    • Contact: Benjamin CHOUSTERMAN, MD; Email: benjamin.chousterman@aphp.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Hospitalized patients in intensive care unit suffering from mechanically ventilated ARDS as defined by Matthay et al.

Description

Inclusion Criteria:

• ARDS risk factors: bacterial or viral pneumonia, extrapulmonary infection, major trauma, transfusion, inhalation injury, or shock.
• Pulmonary edema not explained by a cardiogenic cause or volume overload.
• Onset of respiratory symptoms within <7 days.
• Bilateral pulmonary involvement on chest X-ray, CT scan, or ultrasound.
• PaO₂/FiO₂ ≤ 300 assessed with PEEP ≥ 5 cmH₂O.

Exclusion Criteria:

• ARDS with intubation for more than 48 hours.
• Contraindications to bronchoscopy: effective anticoagulation, dual antiplatelet therapy, thrombocytopenia <50 G/L.
• Pre-existing immunodeficiency: active solid tumor or remission <5 years, active hematologic malignancy or remission <5 years, systemic disease (even without specific treatment), solid organ or bone marrow transplant, HIV infection with CD4 <200/mm³.
• Cardiac arrest with a poor prognosis (NSE >60, malignant EEG, diffuse ischemia on imaging, loss of trunk reflexes).
• Patients <18 year-old
• Patients under legal guardianship, curatorship, or deprived of liberty.
• Ongoing pregnancy.
• Patients without social security coverage.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single cell RNA sequencing of pulmonary immune cells	Single cell RNA sequencing of pulmonary immune cells collected during a bronchoalveolar lavage at inclusion.	At baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality rate at day 90	At day 90
Mortality	Mortality rate at one year	1 year
Time without respiratory support	Number of days alive without mechanical ventilation on day 28 after inclusion or on discharge from intensive care if this occurs before the 28th day	At day 28
Length of stay in intensive care	Number of days in intensive care.	From inclusion to ICU discharge up to 1 year
Number of secondary infections	Rate of secondary infections defined as a new prescription of antibiotics	At day 90
Number of secondary infections	Rate of secondary infections defined as a new prescription of antibiotics	1 year
Impact perceived on quality of life	Quality of life assessed though the SF-12 questionnaire on the phone.	At day 90
Impact perceived on quality of life	Rate of secondary infections defined as a new prescription of antibiotics	1 year
Dsypnea scale	Dyspnea scale assessed through mMRC questionnaire on the phone	At day 90
Dsypnea scale	Dyspnea scale assessed through mMRC questionnaire on the phone	1 year
Organ failure	SOFA score assessment	At baseline
Organ failure	SOFA score assessment	At day 7.
Need for vasopressor	Need for vasopressor (epinephrine or norepinephrine)	At baseline
Vasopressor free days	Number of days alive without vasopressors on day 28 after inclusion or on discharge from intensive care if this occurs before the 28th day.	At day 28 or at discharge from intensive care

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2026
• Primary Completion (Estimated): May 11, 2029
• Study Completion (Estimated): May 11, 2029

Study Registration Dates

• First Submitted: January 9, 2026
• First Submitted That Met QC Criteria: February 3, 2026
• First Posted (Actual): February 9, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: acute respiratory distress syndrome; ADRS; subphenotypes
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome
• Other Study ID Numbers: APHP251692

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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