Alveolar Macrophage Programming Following Endotoxin Exposure

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).

Study Overview

• Status: Recruiting
• Conditions: ARDS, Human
• Intervention / Treatment: Other: bronchoscopy with intrabronchial administration of lipopolysaccharide

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kara Mould; Phone Number: 303-398-1787; Email: mouldk@njhealth.org

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health
      • Contact: Kara Mould; Phone Number: 303-398-1787

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LPS arm	Other: bronchoscopy with intrabronchial administration of lipopolysaccharide; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Jewish Health

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2019
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2032

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (Actual): March 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 6, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome
• Other Study ID Numbers: HS-3131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No