Pulmonary Immune Cell-microbiome Interactions in ARDS
ConditionARDS, Human
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorHvidovre University Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
ARDS caused by COVID-19
Absolute contraindications for bronchoscopy
Untreated malignant arrhythmia
Documented or suspected intracranial hypertension (intracranial pressure ≥ > 15 mmHg)
Trial population
Mechanically ventilated adult ICU patients at Hvidovre University Hospital
Trial design
Design model
Case-only
Time perspective
Prospective
Treatments tested in this trial
Bronchoalveolar lavage
Procedure/SurgeryBronchoalveolar lavage in the middle lobe of the right lung and a mini-bronchoalveolar lavage in the upper and lower lobe of the right lung
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: None-mild ARDS1 intervention
Group B: Moderate-severe ARDS1 intervention
Trial outcomes
Primary outcomes
1
Lung microbiome
16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage flui
Time frame
Day 0 (subsequent to study inclusion in the ICU)2
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
Time frame
Day 0 (subsequent to study inclusion in the ICU)Secondary outcomes
1
Cell differential counts and cytomorphological analyses of BALF
Time frame
Day 0 (subsequent to study inclusion in the ICU)2
Trans-compartmental fluxes
(calculated from plasma- and urea-adjusted BAL)
Time frame
Day 0 (subsequent to study inclusion in the ICU)3
Auto-antibodies against tI-IFNs in blood
Measured in bronchoalveolarlavage fluid
Time frame
Day 0 (subsequent to study inclusion in the ICU)4
White blood cells counts
Total white blood cells, neutrocytes, lymphocytes, and monocytes in bronchoalveolar lavage fluid and blood
Time frame
Day 0 (subsequent to study inclusion in the ICU)Sponsors and contacts
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Source ClinicalTrials.gov