Alveolar Macrophage Programming Following Endotoxin Exposure

Not Applicable

Recruiting

• Conditions: ARDS, Human
• Interventions: Other: bronchoscopy with intrabronchial administration of lipopolysaccharide

• Registration Number: NCT03859050
• Lead Sponsor: National Jewish Health

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-02-14
• Study First Submitted QC: 2019-02-27
• Study First Posted: 2019-03-01
• Study Start: 2019-03-18
• Status Verified: 2024-07
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-06
• Primary Completion: 2029-07
• Study Completion: 2032-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Written, informed consent
2. Age 18-50

Exclusion Criteria

1. Current or recent illness (past 2 weeks)
2. Presence or prior history of cardiac, pulmonary or systemic disease
3. Bleeding disorder, use of systemic anticoagulants or antiplatelet therapy
4. American Society of Anesthesiology (ASA) class 2 or greater
5. Immunocompromised state (HIV, immunoglobulin deficiency, systemic immunosuppressants)
6. 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
7. Alcohol use disorder or greater than 7 drinks/week for women or greater than 14 drinks/week for men in the past 3 months
8. Allergy or prior adverse reaction to lidocaine, midazolam or fentanyl
9. Abnormal spirometry or electrocardiogram at time of screening
10. Pregnant (based on urine pregnancy test) or breast feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LPS arm	bronchoscopy with intrabronchial administration of lipopolysaccharide	-

Primary Outcome Measures

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

Trial Locations

Locations (1)

National Jewish Health; 🇺🇸 Denver, Colorado, United States