Innate Immunity in Ozone-induced Airway Inflammation in COPD

Pulmonary Disease, Chronic Obstructive Clinical Trial

— CO3PD  

Official title:

Innate Immunity in Ozone-induced Airway Inflammation in COPD

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04669743
• Other study ID #: 15-18223
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 7, 2016
• Est. completion date: October 2024

Study information

• Verified date: June 2022
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

Inclusion Criteria:

Group 1:

1. No diagnosis of COPD or asthma.

2. No spirometric evidence of airflow obstruction as determined by FEV1/FVC ratio = or >0.7.

3. Less than 1 pack year history of tobacco smoking and no tobacco use within the past 12 months.

Group 2:

1. No diagnosis of COPD or asthma.

2. No spirometric evidence of airflow obstruction as determined by FEV1/FVC ratio = or >0.7.

3. Current smoker with history of at least 20 pack-years smoking.

Group 3:

1. Diagnosis of COPD as determined by GOLD criteria (FEV1/FVC ratio <0.7).

2. COPD severity of GOLD stage II or III (FEV1 >40% predicted).

3. Smoking Status: Former smokers with history of at least 20 pack-years smoking.

Group 4:

1. Diagnosis of COPD as determined by GOLD criteria (FEV1/FVC ratio <0.7).

2. COPD severity of GOLD stage II or III (FEV1 >40% predicted).

3. 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:

1. 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.

2. COPD severity of GOLD stage IV.

3. 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).

4. Pregnant/breast feeding.

5. 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.

6. 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.

7. Liver cirrhosis.

8. History of chronic active Hepatitis B or C

9. 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.

Related Conditions & MeSH terms

• Airway Disease
• COPD Exacerbation
• Inflammation
• Pollution Related Respiratory Disorder
• Pollution; Exposure
• Pulmonary Disease, Chronic Obstructive
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

Other:
• Ozone exposure
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.

Locations

Country	Name	City	State
United States	San Francisco VA Medical Center	San Francisco	California
United States	University of California, San Francisco	San Francisco	California
United States	Zuckerberg San Francisco General Hospital and Trauma Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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.	4 weeks
Secondary	Physiologic responses	Quantitative changes across ozone exposure in spirometric indices of airflow obstruction	4 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks
Secondary	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.	4 weeks