Clinical trial NCT05767671: Macrophage Programing in Acute Lung Injury: MiniBAL
Official title: Macrophage Programing in Acute Lung Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
Ventilator Associated Pneumonia
Lead sponsor: National Jewish Health
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-03-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The population to be studied are patients identified to have ARDS, admitted to the intensive care unit, and placed on a mechanical ventilator. Control subjects will be individuals on mechanical ventilation for non-pulmonary reasons (i.e. following surgery, sepsis without lung involvement). A total of 56 subjects will be enrolled. As described below (in Research Methods and Enrollment) a 2:1 ratio of ARDS to control subjects will be targeted.
Primary purpose: BASIC_SCIENCE

Brief summary: 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:

1. How does the immune system respond to different kinds of lung injury and inflammation and how do those processes differ from each other?
2. 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)?
3. 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:

1. Participants will be given 100% oxygen through the breathing machine (mechanical ventilator) for 3-5 minutes. This is called pre-oxygenation.
2. 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.
3. The fluid will be removed with suction and will be sent to the laboratory for testing.
4. 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.
5. Two nasal brushings will be taken from the participants' nose.
6. 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
7. 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.
8. 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.
9. 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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 between ages 18 and 85 years ikd
* Admission to the intensive care unit.
* Orally/nasally intubated or expected to be intubated within 48 hours

Exclusion Criteria:

* 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

Primary outcomes:
measure: Evaluate host response to ARDS
timeFrame: Days on ventilator 1-2, 4-6 and 8-10
measure: Macrophage signaling
timeFrame: Days on ventilator 1-2, 4-6 and 8-10
measure: Resident alveolar Macrophages
timeFrame: Days on ventilator 1-2, 4-6 and 8-10
measure: Recruited versus resident macrophages
timeFrame: Days on ventilator 1-2, 4-6 and 8-10
Secondary outcomes:
measure: Ventilator associated pneumonia (VAP)
timeFrame: Days on ventilator 1-2, 4-6 and 8-10
Other outcomes:
Locations:
city: Denver
country: United States
facility: Intermountain Health - St. Joseph's Hospital - National Jewish Health
state: Colorado
Study officials:
References: