Macrophage Programing in Acute Lung Injury
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Evaluate host response to ARDS
研究概览
简要总结
The goal of this observational clinical trial is to learn about the role white blood cells (macrophages) play in lung inflammation in people with Acute Respiratory Distress Syndrome (ARDS). The main questions it aims to answer are:
- How does the immune system respond to different kinds of lung injury and inflammation and how do those processes differ from each other?
- What roles do the cells that live in the lungs (macrophages) play in turning off inflammation? How does their role differ from other cells that are called to the lung to help repair injury (recruited macrophages)?
- Will more frequent testing of lung cell samples help reduce the time it takes to start treatment for ventilator-associated pneumonia (VAP) and therefore reduce the rates of initial therapy failure?
Participants will be in the intensive care unit (ICU) on a mechanical ventilator (machine that helps patients breathe) because they have ARDS or are on a mechanical ventilator for some other reason (control group). The following will happen:
- Participants will be given 100% oxygen through the breathing machine (mechanical ventilator) for 3-5 minutes. This is called pre-oxygenation.
- A lung specialist (pulmonologist), a member of Dr. Janssen's research team, or respiratory therapist will place small amount of saline into the lung using a long catheter going through the breathing tube.
- The fluid will be removed with suction and will be sent to the laboratory for testing.
- This will be repeated two more times over the course of 10 days, or less if participants are taken off of the ventilator. The procedure will be performed no more than three times.
- Two nasal brushings will be taken from the participants' nose.
- Approximately 3 tablespoons of blood will be removed by putting a needle into the participants vein. This is the standard method used to obtain blood for tests. A total of 9 tablespoons will be taken for research purposes over the course of this study
- Data including the participants age, sex, severity of illness, and other medical conditions will be recorded to determine how these can affect the white blood cells.
- If bacteria are isolated from the fluid in the participants lung, the participants' physician may choose to place the participants on antibiotics to treat an infection.
- A follow-up phone call may be made by a member of the research team after discharge from the hospital. At this time, the participant may be invited to participate in the Post-ICU clinic at National Jewish Health.
详细描述
This research study is looking at the role of white blood cells in acute respiratory distress syndrome (ARDS). ARDS is a severe, life-threatening disease caused by uncontrolled inflammation in the lungs. Macrophages are a type of white blood cell that is involved in both causing and removing inflammation. The goal of this study is to learn more about macrophages in the setting of ARDS, so that the investigators can potentially find new treatments for this disease. To get the best information for this study, macrophages from patients with ARDS will be compared to macrophages from individuals with healthy lungs.
All participants in this study must be on a breathing machine (mechanical ventilator). Participants must either have damage to the lungs (ARDS) or have healthy lungs with no prior history of lung disease. Participants must fit into one of these categories. For this study, the investigators will isolate macrophages from a sample of fluid obtained from the lungs. While the method used to obtain the sample of fluid is a standard procedure performed in the ICU, the investigators will be performing it for research purposes. The investigators will also be collecting two nasal brushes. During the nasal brushing a small brush will be inserted into the first one or two inches of the participants nasal cavity from the participants nostril by a member of the research team. The brush will be moved back and forth gently, then removed. A second brush will be inserted in the other nostril and the technique repeated. A second part of our study is to determine whether regularly sampling fluid from the lungs and looking for bacteria will help us catch and treat pneumonia quicker. As such, a portion of the fluid obtained from the lungs, will be sent to the laboratory to look for bacteria growing in the lung.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent (by LAR if subject unconscious or has altered mental status) prior to any study procedures. Verbal consent may be used as necessary
- •Adults greater than 18 years of age
- •Admission to the intensive care unit.
- •Orally/nasally intubated or expected to be intubated within 48 hours
排除标准
- •History of solid organ or bone marrow transplantation
- •Severe or massive hemoptysis
- •At significant risk for bleeding (INR > 3 or PTT > 3x normal)
- •Presence of pneumomediastinum or pneumothorax on recent imaging
- •Presence of an advanced directive with Do Not Intubate (DNI) status (Do Not Resuscitate (DNR) is acceptable)
- •Morbid state or expected to survive less than 24 hours because of an advanced co-morbid medical condition in the opinion of the PI and/or clinical team and attending physician.
- •Pregnancy
研究组 & 干预措施
Study Population Group
People in the ICU on mechanical ventilation due to a diagnosis of ARDS or any other diagnosis that requires mechanical ventilation (following surgery, sepsis without lung involvement, seizures)
干预措施: Non-Bronchoscopic Mini Bronchoalveolar Lavage (Other)
结局指标
主要结局
Evaluate host response to ARDS
时间窗: Days on ventilator 1-2, 4-6 and 8-10
Compare host response due to ARDS caused by COVID19 versus other forms of ARDS and to determine how resident and recruited macrophages influence inflammation during ARDS and how they differentially contribute to lung repair.
Macrophage signaling
时间窗: Days on ventilator 1-2, 4-6 and 8-10
1\. The host response to COVID19 includes a robust inflammatory response with exceedingly high levels of pro-inflammatory cytokines such as IL-6. We hypothesize that macrophage signaling plays a major role in these responses.
Resident alveolar Macrophages
时间窗: Days on ventilator 1-2, 4-6 and 8-10
2\. Resident alveolar macrophages will remain constant in number throughout the course of ARDS whereas recruited macrophages will increase in number and then ultimately undergo apoptosis as inflammation resolves. Alveolar macrophages will be isolated from mini BAL of ARDS subjects and mechanically ventilated controls. Macrophage subsets will be distinguished with flow cytometry and enumerated.
Recruited versus resident macrophages
时间窗: Days on ventilator 1-2, 4-6 and 8-10
3\. Recruited macrophages from ARDS subjects will be more pro-inflammatory than resident macrophages at early time points (i.e. days 1-2) and produce pro-reparative molecules at later time points. Macrophage subsets will be isolated using FACS and subjected to RNA sequencing. Pro-inflammatory and pro-reparative modules will be assessed in the data set expression of transcription factors reported to drive macrophage polarization (HIF-1α, NF-kB, STAT-1, STAT-3, STAT-6, PPARγ, PU.1) will be assessed. Macrophages from control subjects will be used to determine baseline activation and transcriptional status.
次要结局
- Ventilator associated pneumonia (VAP)(Days on ventilator 1-2, 4-6 and 8-10)
研究者
William Janssen, MD
Section Head of Critical Care, Professor of Medicine, Principle Investigator
National Jewish Health