Alveolar Macrophage Programming Following Endotoxin Exposure

Study Overview
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Brief Summary
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The histologic hallmarks of lung inflammation include 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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Alveolar Macrophage Programming Following Endotoxin Exposure

Conditions
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ARDS, Human

Intervention / Treatment
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* Other: bronchoscopy with intrabronchial administration of lipopolysaccharide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written, informed consent Age 18-50 Exclusion Criteria: Current or recent illness (past 2 weeks) Presence or prior history of cardiac, pulmonary or systemic disease Bleeding disorder, use of systemic anticoagulants or antiplatelet therapy American Society of Anesthesiology (ASA) class 2 or greater Immunocompromised state (HIV, immunoglobulin deficiency, systemic immunosuppressants) Use of any inhaled substance, including tobacco, marijuana, e-cigarrettes, cocaine, methamphetamines, or toxic vapors in the past 3 months or greater than 10 pack-year smoking history Alcohol use disorder or greater than 7 drinks/week for women or greater than 14 drinks/week for men in the past 3 months Allergy or prior adverse reaction to lidocaine, midazolam or fentanyl Abnormal spirometry or electrocardiogram at time of screening Pregnant (based on urine pregnancy test) or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LPS arm<br> | Other: bronchoscopy with intrabronchial administration of lipopolysaccharide<br>* The PI will administer intrabronchial LPS into the lungs of healthy volunteers and then obtaining macrophages by bronchoalveolar lavage (BAL) 24, 48, 72, 96, or 120 hours later.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resident alveolar macrophages and recruited macrophages will be distinguished from one another using multi-parameter flow cytometry, and the relative proportions enumerated | Resident and recruited macrophages will be purified using fluorescence activated cell sorting (FACS) and subjected to RNA sequencing. | 7 days |