Back to resultsInnate Immunity in Ozone-induced Airway Inflammation in COPD (CO3PD)
Primary Purpose
Pulmonary Disease, Chronic Obstructive, Airway Disease, COPD Exacerbation
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ozone exposure
Sponsored by
About this trial
This is an interventional other trial for Pulmonary Disease, Chronic Obstructive focused on measuring ozone, airway macrophages, air pollution, COPD exacerbation, Phagocytosis, Efferocytosis, Mass cytometry
Eligibility Criteria
Inclusion Criteria:
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).
- Smoking Status: Current smokers with history of at least 20 pack-years smoking.
During subject screening visit, Albuterol is used to determine whether the subjects have COPD based on the Global Initiative on Obstructive Lung Diseases (GOLD) criteria. Regardless of whether the subject has reversibility to Albuterol or not, if they have an abnormal ratio after inhalation of Albuterol, they would meet the GOLD criteria for COPD and will be included in the study.
Exclusion Criteria:
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.
Sites / Locations
- Zuckerberg San Francisco General Hospital and Trauma Center
- San Francisco VA Medical Center
- University of California, San Francisco
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Study Population
Arm Description
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.
Outcomes
Primary Outcome Measures
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)
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)
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)
Secondary Outcome Measures
Symptomatic responses
Evidence for presence of mild exacerbation as measured by changes at or above the level of minimally clinically important difference (MCID) in each of the questionnaire's symptom score, 1-6, for the number of flare-ups in the past 3 years, with 6 being the worst outcome.
Physiologic responses
Quantitative changes across ozone exposure in spirometric indices of airflow obstruction
Cardiovascular response using measurement of Heart Rate
Cardiovascular outcome of heart rate will be measured for safety assessment before, during, and after ozone exposure. The maximum limit of their heart rate is 80% of their heart rate maximum.
Cardiovascular response using measurement of Blood Pressure
Cardiovascular outcome of blood pressure (both systolic and diastolic) will be measured for safety assessment before, during, and after ozone exposure.
Cardiovascular response using measurement of ECG changes
Cardiovascular outcomes of electrocardiogram (ECG) changes will be measured for safety assessment before and after ozone exposure. ECG changes, including ST-segment elevation and rhythm abnormalities, will be compared to the baseline ECG.
Full Information
NCT ID
NCT04669743
First Posted
December 14, 2018
Last Updated
June 6, 2022
Sponsor
University of California, San Francisco
1. Study Identification
Unique Protocol Identification Number
NCT04669743
Brief Title
Innate Immunity in Ozone-induced Airway Inflammation in COPD
Acronym
CO3PD
Official Title
Innate Immunity in Ozone-induced Airway Inflammation in COPD
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 7, 2016 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
A major cause of morbidity and mortality in COPD is exacerbation. The mechanisms underlying COPD exacerbation are poorly understood, but airway innate immune system has been implicated in its development. Air pollution contributes to development of COPD exacerbation, and exposure to ozone, a major component of air pollution, is associated with increased healthcare utilization among patients with COPD. Inhalation of ambient levels of ozone is known to affect airway innate immune system. This proposal sets out to characterize and investigate the role of innate immune system and in particular airway macrophages in ozone-induced COPD exacerbation through establishing an experimental model that employs controlled ozone exposure and longitudinal sampling via bronchoscopy. The research plan proposes to examine human immune cells trafficking in airways during the process of ozone-induced airway injury and inflammation in patients with COPD. The investigator's overall hypothesis is that inhalational challenge to a high ambient level of ozone in patients with COPD provides a safe human model of airway injury with resulting intraluminal shifts in the population and polarization of macrophages to study innate immunity processes relevant to ozone-induced COPD exacerbation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Controlled inhalational challenge to ozone
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Study Population
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Ozone exposure
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in prevalence and functional status of alveolar macrophage sub-populations in airway lumen
Description
Number of alveolar macrophages (AM) measured by flow cytometry (both absolute numbers and relative percentage of cells)
Time Frame
4 weeks
Title
Changes in prevalence and functional status of monocyte-derived macrophage sub-populations in airway lumen
Description
Number of monocyte-derived macrophages (MDM) measured by flow cytometry (both absolute numbers and relative percentage of cells)
Time Frame
4 weeks
Title
Changes in prevalence and functional status of interstitial macrophage sub-populations in airway lumen
Description
Number of interstitial macrophages (IM) measured by flow cytometry (both absolute numbers and relative percentage of cells)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Symptomatic responses
Description
Evidence for presence of mild exacerbation as measured by changes at or above the level of minimally clinically important difference (MCID) in each of the questionnaire's symptom score, 1-6, for the number of flare-ups in the past 3 years, with 6 being the worst outcome.
Time Frame
4 weeks
Title
Physiologic responses
Description
Quantitative changes across ozone exposure in spirometric indices of airflow obstruction
Time Frame
4 weeks
Title
Cardiovascular response using measurement of Heart Rate
Description
Cardiovascular outcome of heart rate will be measured for safety assessment before, during, and after ozone exposure. The maximum limit of their heart rate is 80% of their heart rate maximum.
Time Frame
4 weeks
Title
Cardiovascular response using measurement of Blood Pressure
Description
Cardiovascular outcome of blood pressure (both systolic and diastolic) will be measured for safety assessment before, during, and after ozone exposure.
Time Frame
4 weeks
Title
Cardiovascular response using measurement of ECG changes
Description
Cardiovascular outcomes of electrocardiogram (ECG) changes will be measured for safety assessment before and after ozone exposure. ECG changes, including ST-segment elevation and rhythm abnormalities, will be compared to the baseline ECG.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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).
Smoking Status: Current smokers with history of at least 20 pack-years smoking.
During subject screening visit, Albuterol is used to determine whether the subjects have COPD based on the Global Initiative on Obstructive Lung Diseases (GOLD) criteria. Regardless of whether the subject has reversibility to Albuterol or not, if they have an abnormal ratio after inhalation of Albuterol, they would meet the GOLD criteria for COPD and will be included in the study.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mehrdad Arjomandi, M.D.
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zuckerberg San Francisco General Hospital and Trauma Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
San Francisco VA Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94121
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94122
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Innate Immunity in Ozone-induced Airway Inflammation in COPD
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