Macrophage Programing in Acute Lung Injury

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Procedure: Mini bal

• Study Type: Observational
• Enrollment (Anticipated): 56

Contacts and Locations

• Study Contact: Name: Christine Griesmer, MPH; Phone Number: 303-398-1325; Email: griesmerc@njhealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The population to be studied are patients identified to have ARDS, admitted to the intensive care unit, and placed on a mechanical ventilator. The MICU at National Jewish-St Joseph Hospital will be the primary site for enrollment. 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.

Description

Inclusion Criteria:

1. Written, informed consent (by surrogate if unconscious or if altered mental status)
2. Admission to a Medical Intensive care unit
3. Orally/nasally intubated, evaluable within 24 h of intubation or onset of ARDS
4. Expected to remain mechanically ventilated for at least 48 h after the first study procedure.

Exclusion Criteria:

1. 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).
2. History of solid organ or bone marrow transplantation
3. History of chronic lung disease (e.g. COPD, pulmonary fibrosis, cystic fibrosis)
4. Human immunodeficiency virus positivity
5. Severe or massive hemoptysis
6. At significant risk for bleeding (INR > 3 or PTT > 3x normal)
7. Presence of an advanced directive to withhold life-sustaining treatment
8. Morbid state or expected to survive less than 14 days because of an advanced co-morbid medical condition;
9. Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Jewish Health

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: February 12, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 21, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: HS-3076

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No