ARDS, Human Clinical Trial
— ILLUMINA-1Official title:
Pulmonary Immune Cell-microbiome Interactions in Acute Respiratory Distress Syndrome: The ILLUMINA-1 Study
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.
Status | Recruiting |
Enrollment | 40 |
Est. completion date | November 30, 2028 |
Est. primary completion date | November 30, 2028 |
Accepts healthy volunteers | |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Inclusion criteria - moderate-to-severe ARDS - 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 Inclusion criteria - none-to-mild ARDS - 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 Exclusion Criteria: - 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 |
Country | Name | City | State |
---|---|---|---|
Denmark | Hvidovre Hospital, University of Copenhagen | Hvidovre |
Lead Sponsor | Collaborator |
---|---|
Hvidovre University Hospital |
Denmark,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | |
Primary | 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 | Cell differential counts and cytomorphological analyses of BALF | Day 0 (subsequent to study inclusion in the ICU) | ||
Secondary | Trans-compartmental fluxes | (calculated from plasma- and urea-adjusted BAL) | Day 0 (subsequent to study inclusion in the ICU) | |
Secondary | Auto-antibodies against tI-IFNs in blood | Measured in bronchoalveolarlavage fluid | Day 0 (subsequent to study inclusion in the ICU) | |
Secondary | White blood cells counts | Total white blood cells, neutrocytes, lymphocytes, and monocytes in bronchoalveolar lavage fluid and blood | Day 0 (subsequent to study inclusion in the ICU) | |
Secondary | Cytokines | Multiplex assay for measuring cytokines in bronchoalveolar lavage fluid and plasma (e.g. IL-1-beta, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-33, IL-35, TGF-beta, TNF-alpha, HMGB1) | Day 0 (subsequent to study inclusion in the ICU) | |
Secondary | Number and characterizations of respiratory pathogens | Respiratory filmarray PCR for testing for number of pathogens | Day 0 (subsequent to study inclusion in the ICU) | |
Secondary | Number and characterizations of microorganisms | Growth of pathogenic microorganisms in body fluids (e.g. urine, blood, bronchoalveolar lavage fluid) in microbiological assays | Up to 12 weeks |
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