Pulmonary Disease, Chronic ObstructiveCO3PDNCT04669743
Innate Immunity in Ozone-induced Airway Inflammation in COPD
A study testing Ozone exposure in people with Pulmonary Disease, Chronic Obstructive and Airway Disease, run by University of California, San Francisco at 3 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 45 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive, Airway Disease, COPD Exacerbation
- What is being tested?
- Ozone exposure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 3 sitesUnited States
- Study dates
- 7 Apr 2016to 31 Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Zuckerberg San Francisco General Hospital and Trauma Center
San Francisco, California, 94110
San Francisco VA Medical Center
San Francisco, California, 94121
University of California, San Francisco
San Francisco, California, 94122
About this study
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.
Read the 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.
- Conditions
- Pulmonary Disease, Chronic Obstructive, Airway Disease, COPD Exacerbation, Pollution; Exposure, Pollution Related Respiratory Disorder
- Being tested
- Ozone exposure
- Keywords
- ozone, airway macrophages, air pollution, COPD exacerbation, Phagocytosis, Efferocytosis, Mass cytometry
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ozone exposureOther
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Ozone exposure |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 4 weeks
Secondary outcomes (5)
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.
Measured: 4 weeks
Physiologic responses
Quantitative changes across ozone exposure in spirometric indices of airflow obstruction
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
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.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start7 Apr 2016
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Controlled inhalational challenge to ozone
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mehrdad Arjomandi, M.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04669743
- Sponsor's protocol ID
- 15-18223
- Acronym
- CO3PD
- Status last verified
- Jun 2026
- First submitted
- 14 Dec 2018
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Innate Immunity in Ozone-induced Airway Inflammation in COPD
- ClinicalTrials.gov ID
- NCT04669743
- Acronym / sponsor ID
- CO3PD / 15-18223
- 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
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 7 Apr 2016 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 17 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Controlled inhalational challenge to ozone
| Arm | Type | Receives |
|---|---|---|
| Study Population | Experimental | Other: Ozone exposureSubjects 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. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
- No diagnosis of COPD or asthma.
- No spirometric evidence of airflow obstruction as determined by FEV1/FVC ratio = or >0.7.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ozone exposureExposures 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. | Other | Study Population |
Primary outcome
Changes in prevalence and functional status of alveolar macrophage sub-populations in airway lumen
Time frame: 4 weeks
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
Time frame: 4 weeks
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
Time frame: 4 weeks
Number of interstitial macrophages (IM) measured by flow cytometry (both absolute numbers and relative percentage of cells)
5 secondary outcomes
Symptomatic responses
Time frame: 4 weeks
Physiologic responses
Time frame: 4 weeks
Cardiovascular response using measurement of Heart Rate
Time frame: 4 weeks
Cardiovascular response using measurement of Blood Pressure
Time frame: 4 weeks
Cardiovascular response using measurement of ECG changes
Time frame: 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mehrdad Arjomandi, M.D. principal investigator
University of California, San Francisco
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ozone exposure in people with Pulmonary Disease, Chronic Obstructive and Airway Disease, run by University of California, San Francisco at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in prevalence and functional status of alveolar macrophage sub-populations in airway lumen (time frame: 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.