Pulmonary Immune Cell-microbiome Interactions in ARDS

NCT05795257 | Recruiting

• 1 other identifier: H-22046755
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The overall aim is to compare the composition and spatial heterogeneity of the following in critically ill intensive care unit (ICU) patients: i) immune cell populations and their activation patterns, ii) the surrounding cytokine-chemokine milieu, including trans-compartmental fluxes of these mediators between the lung and bloodstream, and iii) the lung microbiome. Main hypotheses:

• The immune cell population in bronchoalveolar lavage fluid (BALF) from patients with ARDS is dominated by neutrocytes, while T cells are depleted, and show evidence of hyper-activation and exhaustion
• T cell hyper-activation and exhaustion is specifically compartmentalised to the lungs, and much more pronounced in moderate-to-severe than none-to-mild ARDS
• Cyto- and chemokines derived from pulmonary immune cells are higher in moderate-to-severe than none-to-mild ARDS with a greater release from lungs to the bloodstream, notably of IL-6 and IL-8.
• The differences in T cell profile in BALF, notably the ratio between regulatory T cells and T helper 17 cells, will change with disease severity over time, and can be explained by the presence of tI-IFN antibodies and/or a low microbial diversity of the respiratory tract with low enrichment from the oral cavity.

Conditions

ARDS, Human

Outcome Measures

Primary Outcomes (2)

• Lung microbiome

  16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage flui

  Day 0 (subsequent to study inclusion in the ICU)

• Lymphocyte populations

  Cell populations and subpopulations evaluated by 10 colored flow cytometry (B cells, T cells, TCR subsets, Tregs/Th17, dendritic cells, myeloid cells and neutrophils) in bronchoalveolar lavage fluid and blood

  Day 0 (subsequent to study inclusion in the ICU)

Secondary Outcomes (7)

• Cell differential counts and cytomorphological analyses of BALF

  Day 0 (subsequent to study inclusion in the ICU)

• Trans-compartmental fluxes

  Day 0 (subsequent to study inclusion in the ICU)

• Auto-antibodies against tI-IFNs in blood

  Day 0 (subsequent to study inclusion in the ICU)

• White blood cells counts

  Day 0 (subsequent to study inclusion in the ICU)

• Cytokines

  Day 0 (subsequent to study inclusion in the ICU)

Study Arms (2)

None-mild ARDS

Procedure: Bronchoalveolar lavage

Moderate-severe ARDS

Procedure: Bronchoalveolar lavage

Interventions

Bronchoalveolar lavage PROCEDURE

Bronchoalveolar lavage in the middle lobe of the right lung and a mini-bronchoalveolar lavage in the upper and lower lobe of the right lung

Moderate-severe ARDS; None-mild ARDS

Eligibility Criteria

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

Study Population

Mechanically ventilated adult ICU patients at Hvidovre University Hospital

You may qualify if:

• Admitted to the ICU at Hvidovre Hospital
• Intubated within the past 72 hours
• Moderate-to-severe ARDS according to the Berlin definition19
• Age ≥ 18 years
• Admitted to the ICU at Hvidovre Hospital
• Intubated within the past 72 hours
• None-to-mild ARDS according to the Berlin definition19
• Age ≥ 18 years

You may not qualify if:

• ARDS caused by COVID-19
• Absolute contraindications for bronchoscopy
• Untreated malignant arrhythmia
• Documented or suspected intracranial hypertension (intracranial pressure ≥ \> 15 mmHg)
• One-lung ventilation
• Severe coagulopathy

Sponsors & Collaborators

• Hvidovre University Hospital: lead

Study Sites (1)

Hvidovre Hospital, University of Copenhagen

Hvidovre, 2650, Denmark

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, BAL fluid, endotracheal aspirate, oral/nasal swab

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Bronchoalveolar Lavage

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Therapeutic Irrigation; Investigative Techniques

Study Officials

• MD PhD Ronan berg

  Biomedical Science of Health, University of Copenhagen

  STUDY CHAIR

Central Study Contacts

MD, PhD, Ronni Plovsing

CONTACT

+45386220721; ronni.thermann.reitz.plovsing.01@regionh.dk

MD Katrine Schneider

CONTACT

+4528118147; katrine.schneider@regionh.dk

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor, Senior Consultant of ICU

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 3, 2023
• Study Start: March 14, 2023
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: March 17, 2025

Record last verified: 2025-03

Locations

DK (1)