Pulmonary Immune Cell-microbiome Interactions in Acute Respiratory Distress Syndrome: the ILLUMINA-1 Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Lymphocyte populations
研究概览
简要总结
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.
详细描述
Background Pulmonary hyperinflammation with neutrocyte and macrophage invasion and T cell depletion are common features of the acute respiratory distress syndrome (ARDS), but it remains to be elucidated whether the T cells in the lungs of patients with ARDS are hyperactivated and/or exhausted, and to which extent this contributes to neutrocyte invasion and thus lung tissue destruction. Furthermore, the pulmonary microbiome has shown a reduction in diversity and interactions in ARDS, which may be important for normal T cell function. At present, immune cell-microbiome interactions and their relation to disease severity and progression have not yet been studied in ARDS.
Overall design In 20 mechanically ventilated patients with none-to-mild and 20 with moderate-to-severe non-COVID-19 ARDS according to the Berlin definition an endotracheal aspirate and BAL fluid (BALF) from separate lung segments will be obtained. Furthermore, an oral and nasal swab and blood samples will be collected. This will be done within 72 hours after intubation, and again after 7-10 days if the patient is still intubated.
Patient's electronic health record The following is obtained after inclusion: diagnosis codes and medication (type and dosage, including vasopressors and sedatives), and smoking history (current/previous/never smoker; pack years); admission time; blood pressure, heart rhythm and heart rate, temperature, ventilator settings, supportive care (dialysis, ECMO), blood tests results at admission and on the study days (blood cell counts, coagulation parameters, renal, liver, and electrolyte panel; arterial and mixed venous blood gases); clinical scores at admission and on the study days (SAPS3, APACHE II, SOFA), death within 30 days
Blood sampling Arterial blood samples are drawn from the patient's invasive arterial catheter (inserted at ICU admission for clinical purposes: for continuous invasive blood pressure monitoring and repeated arterial blood gas collection) immediately before BALF collection.
Bronchoscopy with BALF collection This procedure is performed in a standardized fashion according to current clinical guidelines. Immediately prior to the procedure, an oral swab, nasal swab and an endotracheal aspirate (ETA) are obtained. FIO2 is then increased to 1.0, and the bronchoscopy procedure is performed using a disposable videoscope with an outer diameter of 5.0 mm). Three successive 50-ml aliquots of prewarmed (37°C) isotonic saline are instilled in the medial segment of the right middle lobe, aspirated immediately with low negative suction pressure (< 100 cm H2O), and pooled into a sterile glass container on ice to obtain a BALF specimen.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Lymphocyte populations
时间窗: Day 0 (subsequent to study inclusion in the ICU)
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
Lung microbiome
时间窗: Day 0 (subsequent to study inclusion in the ICU)
16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage flui
次要结局
- Auto-antibodies against tI-IFNs in blood(Day 0 (subsequent to study inclusion in the ICU))
- Cytokines(Day 0 (subsequent to study inclusion in the ICU))
- Number and characterizations of respiratory pathogens(Day 0 (subsequent to study inclusion in the ICU))
- Number and characterizations of microorganisms(Up to 12 weeks)
- White blood cells counts(Day 0 (subsequent to study inclusion in the ICU))
- 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))
研究者
Ronni R. Plovsing
Associate professor, Senior Consultant of ICU
Hvidovre University Hospital