Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
Not provided
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:
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:
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study Population Group | Other | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Non-Bronchoscopic Mini Bronchoalveolar Lavage | Other | A 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Days on ventilator 1-2, 4-6 and 8-10 |
| 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. | Days on ventilator 1-2, 4-6 and 8-10 |
| 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. | Days on ventilator 1-2, 4-6 and 8-10 |
| 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. | Days on ventilator 1-2, 4-6 and 8-10 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Olivia VerBurg | Contact | 303-398-1201 | verburgo@njhealth.org | |
| William Janssen, MD | Contact |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Intermountain Health - St. Joseph's Hospital - National Jewish Health | Recruiting | Denver | Colorado | 80218 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| D053717 | Pneumonia, Ventilator-Associated |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D000077299 | Healthcare-Associated Pneumonia |
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
|
| Days on ventilator 1-2, 4-6 and 8-10 |
| D003428 | Cross Infection |
| D007239 | Infections |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007049 | Iatrogenic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |