Macrophage Programing in Acute Lung Injury

Study Overview
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Brief Summary
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The histologic hallmarks of lung inflammation and in the extreme, acute respiratory distress syndrome (ARDS), include intense accumulation of inflammatory cells in the airspaces and interstitium, injury to alveolar epithelial and endothelial cells, loss of epithelial-capillary integrity and accumulation of edema fluid in the interstitium and airspaces. Accordingly, for alveolar repair to occur inflammation must be halted, debris and inflammatory cells removed, injured tissue cells replaced, and capillary barrier function re-established. Macrophages are key players in all of these. Here the investigators hypothesize that resident alveolar macrophages and recruited macrophages serve completely different functions, acting independently (i.e. division of labor) yet cooperatively (synergism).

Official Title
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Macrophage Programing in Acute Lung Injury

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Procedure: Mini bal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written, informed consent (by surrogate if unconscious or if altered mental status) Admission to a Medical Intensive care unit Orally/nasally intubated, evaluable within 24 h of intubation or onset of ARDS Expected to remain mechanically ventilated for at least 48 h after the first study procedure. Exclusion Criteria: Treatment with immunosuppressants in the prior 3 months (antineoplastic agents, tumor necrosis factor alpha antagonists, cyclosporine, methotrexate, azathioprine, or mycophenolate. Treatment with glucocorticoids for septic shock is acceptable). History of solid organ or bone marrow transplantation History of chronic lung disease (e.g. COPD, pulmonary fibrosis, cystic fibrosis) Human immunodeficiency virus positivity Severe or massive hemoptysis At significant risk for bleeding (INR > 3 or PTT > 3x normal) Presence of an advanced directive to withhold life-sustaining treatment Morbid state or expected to survive less than 14 days because of an advanced co-morbid medical condition; Pregnancy
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Mini bal|Mini-BAL is a minimally invasive technique frequently used in the investigator's local intensive care units (ICUs) to obtain alveolar fluid samples from mechanically ventilated patients. This is typically done for microbial analysis.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation and roles of macrophages during ARDS | Evaluation of resident alveolar macrophages will be distinguished with flow cytometry and enumerated | 10 days | 
| Evaluation and roles of macrophages during ARDS | Evaluation of recruited alveolar macrophages 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. | 10 days |