Innate Immunity in Ozone-induced Airway Inflammation in COPD

NCT04669743 | Unknown DMC

• 1 other identifier: 15-18223
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 3

Brief Summary

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. Patients with COPD are routinely exposed to indoor and outdoor air pollution, which appears to cause escalation of their respiratory symptoms, a process called exacerbation, with resulting need to seek medical attention. This research plan proposes to evaluate the impact of lung immune cells in susceptibility to develop exacerbation through an experimental model of inhalational exposure using ambient levels of a component of air pollution (ozone) in COPD patients and longitudinal sampling of their lung immune cells.

Conditions

Pulmonary Disease, Chronic Obstructive; Airway Disease; COPD Exacerbation; Pollution; Exposure; Pollution Related Respiratory Disorder

Keywords

ozone; airway macrophages; air pollution; COPD exacerbation; Phagocytosis; Efferocytosis; Mass cytometry

Outcome Measures

Primary Outcomes (3)

• Changes in prevalence and functional status of alveolar macrophage sub-populations in airway lumen

  Number of alveolar macrophages (AM) measured by flow cytometry (both absolute numbers and relative percentage of cells)

  4 weeks

• Changes in prevalence and functional status of monocyte-derived macrophage sub-populations in airway lumen

  Number of monocyte-derived macrophages (MDM) measured by flow cytometry (both absolute numbers and relative percentage of cells)

  4 weeks

• Changes in prevalence and functional status of interstitial macrophage sub-populations in airway lumen

  Number of interstitial macrophages (IM) measured by flow cytometry (both absolute numbers and relative percentage of cells)

  4 weeks

Secondary Outcomes (5)

• Symptomatic responses

  4 weeks

• Physiologic responses

  4 weeks

• Cardiovascular response using measurement of Heart Rate

  4 weeks

• Cardiovascular response using measurement of Blood Pressure

  4 weeks

• Cardiovascular response using measurement of ECG changes

  4 weeks

Study Arms (1)

Study Population

EXPERIMENTAL

Subjects will be recruited and consented following screening. Subjects will be characterized into cohorts based on presence of COPD and smoking status. All subjects enrolled will be undergoing the same interventions: 1st Bronchoscopy (3 wks pre-exposure), Ozone Exposure, 2nd Bronchoscopy (1 day post-exposure), 3rd Bronchoscopy (5 days post-exposure). Ozone exposure will take place in an exposure chamber.

Other: Ozone exposure

Interventions

Ozone exposure OTHER

Exposures will take place at the UCSF Human Exposure Chamber Core Facility. Ozone will be added to the air in the chamber and concentration measured every 30 seconds. Subjects will exercise for two 15-minute intervals of each hour on a cycle ergometer, and will rest for two 15-minute intervals between exercise sessions. The rate of exercise will be individually adjusted to produce a targeted minute ventilation of 15-20 L/min/m2 body surface area. Subjects will be sent home post-exposure and will return to the laboratory on the following day and six days after the exposure for bronchoscopy.

Study Population

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Group 1:
• No diagnosis of COPD or asthma.
• No spirometric evidence of airflow obstruction as determined by FEV1/FVC ratio = or \>0.7.
• Less than 1 pack year history of tobacco smoking and no tobacco use within the past 12 months.
• Group 2:
• No diagnosis of COPD or asthma.
• No spirometric evidence of airflow obstruction as determined by FEV1/FVC ratio = or \>0.7.
• Current smoker with history of at least 20 pack-years smoking.
• Group 3:
• Diagnosis of COPD as determined by GOLD criteria (FEV1/FVC ratio \<0.7).
• COPD severity of GOLD stage II or III (FEV1 \>40% predicted).
• Smoking Status: Former smokers with history of at least 20 pack-years smoking.
• Group 4:
• Diagnosis of COPD as determined by GOLD criteria (FEV1/FVC ratio \<0.7).
• COPD severity of GOLD stage II or III (FEV1 \>40% predicted).

You may not qualify if:

• History of IV drug use or inhalation of recreational drugs other than marijuana:
• A- within the past 20 years. B- more than 100 usage. C- longer than 1 year.
• COPD severity of GOLD stage IV.
• Inability to walk briskly or run on treadmill or pedal on ergometer to perform the study-required moderate exercise level (achieve minute ventilation of 15 to 20 L/min/m2 body surface area).
• Pregnant/breast feeding.
• Serious and active heart conditions - defined by stable or unstable angina, recent myocardial infarction (within the last 2 years), active congestive heart failure, ischemic cardiomyopathy.
• Malnourishment - determined by BMI less than 19. If subject has BMI greater or equal to 19, but has a history of malnourishment, study staff will measure albumin level of subject's blood after initial blood draw. Albumin level must be greater than 2.5 mg per deciliter, or subject will be excluded.
• Liver cirrhosis.
• History of chronic active Hepatitis B or C
• On visits where moderate sedation is preformed, subject are required to have an escort home. Inability to secure a ride home will result in the subject being ineligible for the study.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (3)

Zuckerberg San Francisco General Hospital and Trauma Center

San Francisco, California, 94110, United States

Location

San Francisco VA Medical Center

San Francisco, California, 94121, United States

Location

University of California, San Francisco

San Francisco, California, 94122, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mehrdad Arjomandi, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Controlled inhalational challenge to ozone

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 17, 2020
• Study Start: April 7, 2016
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: June 8, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)