Macrophage Programing in Acute Lung Injury: MiniBAL
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-99
SponsorWilliam Janssen, MD
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Non-Bronchoscopic Mini Bronchoalveolar Lavage
Other interventionA minimally invasive technique frequently used in the ICU to obtain alveolar fluid samples from mechanically ventilated patients. The technique uses a commercially available telescoping catheter with a curved distal tip that allows the operator to direct the catheter into the right or left lung. The catheter is passed through an air-tight adapter on the distal end of the endotracheal tube and gently advanced to the desired lung until resistance is encountered. The inner catheter is then advanced until resistance is again encountered, signifying that the distal catheter tip is "wedged." 20ml of sterile saline is instilled into the catheter followed by 5 ml of air, and the fluid aspirated. Two additional 20ml aliquots of sterile saline are injected and aspirated in a similar fashion. Specimens are pooled and on average provide a combined volume of 10ml.
Treatment groups
56 Participants
are divided into 1 treatment groupGroup A: Study Population GroupOther 1 intervention
Trial outcomes
Primary outcomes
1
Evaluate host response to ARDS
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.
Time frame
Days on ventilator 1-2, 4-6 and 8-102
Macrophage signaling
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.
Time frame
Days on ventilator 1-2, 4-6 and 8-103
Resident alveolar Macrophages
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.
Time frame
Days on ventilator 1-2, 4-6 and 8-104
Recruited versus resident macrophages
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.
Time frame
Days on ventilator 1-2, 4-6 and 8-10Secondary outcomes
1
Ventilator associated pneumonia (VAP)
A secondary objective of the study is to reduce time to diagnosis and treatment of ventilator-associated pneumonia (VAP) in an at risk population. All patients on mechanical ventilation are at risk for developing VAP. Prompt administration of antibiotics has been shown to improve mortality. Accordingly appropriate selection of anti-microbial agents is paramount. To assess potential microbial pathogens in the lungs, a 1ml aliquot of each mini-BAL will be sent to the microbiology lab at National Jewish - St. Joseph Hospital to obtain quantitative bacterial cultures, bacterial speciation, and antibiotic sensitivity profiles. These results will be made available to the treating physician and can be used to aid in antibiotic selection and administration.
Time frame
Days on ventilator 1-2, 4-6 and 8-10Sponsors and contacts
Click on the lead sponsor to view all of their trials.
William Janssen, MD
Lead sponsor
National Jewish Health
Sponsor institution
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
Source ClinicalTrials.gov