COPDCOPANCT02236039
COPD Originates in Polluted Air
A study testing Bronchoscopy in people with COPD, run by University of British Columbia at 1 site in Canada.
Trial summary
The investigators are investigating the effects of traffic-related diesel exhaust on lung function and the immune system in those at risk for COPD. The individual will be exposed to either filtered air (FA) or carefully controlled levels of diesel exhaust (DE) in our exposure chamber. Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- COPD
- What is being tested?
- Bronchoscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteCanada
- Study dates
- 27 Oct 2014to 1 May 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 40 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 40-75 years of age
- Free of cardiovascular disease
- Free of insulin-dependent diabetes
- Study participants must agree to adhere to the following medication intake protocol 24 hours prior to study visits:
- participants will be asked to withhold:
- short-acting beta2-agonists (SABAs) for 4 hours prior to testing
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- long-acting beta2-agonists (LABAs) for 12 hours prior to testing if taken in an individual inhaler (different inhaler from inhaled corticosteroid inhaler)
- LABAs and ICS for 24hrs, if those two medication groups are combined in one inhaler
- ICS (if taken alone as a mono-therapy, or if taken with either a LABA or SABA, but in two separate inhaler), for 24 hrs.
- Overall, we are looking for 15 healthy controls without a history of smoking; 20 individuals with a history of smoking, but who have been non-smokers for at least 6 months prior to study participation; and 15 mild-moderate COPD patients (GOLD I and GOLD II).
Who cannot join
- Not between the ages of 40-65 years.
- Are pregnant, breast-feeding, or planning to get pregnant in the following 12 months.
- Are currently using inhaled corticosteroids.
- Are allergic to salbutamol, lidocaine, fentanyl or midazolam.
- Are currently participating in another study that involves taking medications.
- Have unstable COPD symptoms.
Show all 11Show fewer
- Have clinically significant comorbidities (i.e., coronary artery disease).
- Have a history/clinical evidence of asthma.
- Have contraindications to exercise testing.
- Have a body mass index <18.5.
- Regularly use of antihistamines, non-steroidal anti-inflammatories, anticoagulants, acetylsalicylic acid (ASA) or decongestants.
Trial locations and contacts
1 site in 1 country.
Canada1 site
University of British Columbia
Vancouver, British Columbia, V5Z 1M9
About this study
Official title: The Effects of Traffic-Related Air Pollution on Smokers at Risk for Developing COPD
The investigators are investigating the effects of traffic-related diesel exhaust on lung function and the immune system in those at risk for COPD. The individual will be exposed to either filtered air (FA) or carefully controlled levels of diesel exhaust (DE) in our exposure chamber. Post exposure the individual will complete a steady state exercise test. 24h later, a procedure called bronchoscopy (whereby a thin, flexible tube is placed down the throat and into the lungs) will be used so that samples can be collected from the lungs. After 1 month the entire procedure will be repeated with the alternative exposure.
Read the detailed description
- Purpose: To study the effects of traffic related diesel exhaust on people at risk for developing COPD.
- Hypotheses: Hypothesis 1: An increase in proteins, in the exposed lung and blood, that are associated with the pathophysiology of COPD. Hypothesis 2: Air trapping, dyspnea, and impaired exercise tolerance. Such increases will be more pronounced in those with COPD than in control subjects.
- Justification: The use of diesel engines is increasing because they are more fuel-efficient than gasoline engines. However, diesel engines produce different emissions than gasoline engines. Diesel exhaust is emitted from the tailpipe of both "on-road" diesel engine vehicles (diesel cars, buses and trucks) and "non-road" diesel engines (locomotives, marine vessels and some construction equipment). Diesel exhaust consists of both gaseous and particulate air pollutants. People with COPD may be sensitive to air pollution; we would like to know how diesel exhaust (DE) can affects the respiratory and immune systems. We are not expecting that responses will be noticeable to the participant; we are expecting that any responses that may occur will only be detectable through careful examination of cells and tissues (e.g., bronchoalveolar lavage (fluid from lungs), blood). Understanding these subtle changes will help us prevent health problems associated with air pollution in the future.
- Objectives To provide biological plausibility and deepen mechanistic understanding of the emerging epidemiology suggesting a strong role for air pollution in COPD.
- Research Methods:
This is a blinded crossover experiment between two conditions (300 µg/m³ diesel exhaust or filtered air), randomized and counter-balanced to order. Data collection for each condition will be separated by a 4-week washout period.
Prior to the exposure participants will: 1) complete some questionnaires, 2) undergo a set of lung function tests (breathing tests), 3) undergo an incremental exercise test and 4) receive a physical exam by the primary investigator. A small sample of blood and spirometry measurements will also be collected for analysis.
After the exposure another series of exercise and lung function tests will be performed. Blood, spirometry measurements, bronchoalveolar lavage (BAL), endobronchial brushings and biopsies will also be collected for examination of cellular, functional and immunological changes influencing the airways.
- Conditions
- COPD
- Being tested
- Bronchoscopy
- Keywords
- Diesel exhaust, Air pollution, Airway responsivness
- 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.
BronchoscopyProcedure or surgery
Bronchoscopy with biopsy sampling, brushings and bronchoalveolar lavage (BAL) 24 hours post exposure.
| Study group | Role | What they receive |
|---|---|---|
| Filtered air | Active comparator | Exposure for 2 hours to filtered air followed by a bronchoscopy 24 hours post exposure. Receives: Procedure: Bronchoscopy |
| Diesel exhaust | Experimental | Exposure for 2 hours to diesel exhaust followed by a bronchoscopy 24 hours post exposure. Receives: Procedure: Bronchoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokine pattern
BAL, BW, and blood cytokines will be assessed at 24h using immunoassays
Measured: 24 hours
Secondary outcomes (3)
Gene expression
BAL, BW, endobronchial brushings and blood will be used for gene expression. RNA will be isolated using RNeasy and supplemented by assessment of promising candidate genes by real-time RT-PCR
Measured: 24 hours
Cardiopulmonary function
Cardio pulmonary function will be measured at 1.5 hours post exposure using a cardiopulmonary testing system (Vmax)
Measured: 1.5 hours
Cell culture
Airway epithelial cells from the endobronchial brushings will be used for non-immortalized cell culture
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2014 (estimated)
- Study start27 Oct 2014
- Primary completion1 May 2019
- Study completion1 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christopher Carlsten, University of British Columbia
- Investigators
- Christopher Carlsten, MD, MPH, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02236039
- Sponsor's protocol ID
- H14-00821
- Acronym
- COPA
- Status last verified
- Oct 2021
- First submitted
- 11 Aug 2014
- Last updated
- 2 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Behndig AF, Mudway IS, Brown JL, Stenfors N, Helleday R, Duggan ST, Wilson SJ, Boman C, Cassee FR, Frew AJ, Kelly FJ, Sandstrom T, Blomberg A. Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans. Eur Respir J. 2006 Feb;27(2):359-65. doi: 10.1183/09031936.06.00136904.
PubMed 16452593Hsia CC, Hyde DM, Ochs M, Weibel ER; ATS/ERS Joint Task Force on Quantitative Assessment of Lung Structure. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418. doi: 10.1164/rccm.200809-1522ST. No abstract available.
PubMed 20130146Gan, W. Q., J. M. FitzGerald, et al. (2013).
Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet. 2007 Sep 1;370(9589):765-73. doi: 10.1016/S0140-6736(07)61380-4.
PubMed 17765526Rudell B, Ledin MC, Hammarstrom U, Stjernberg N, Lundback B, Sandstrom T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. doi: 10.1136/oem.53.10.658.
PubMed 8943829Schikowski, T., M. Adam, et al. (2014).
McCreanor, J., P. Cullinan, et al. (2007).
Ryu MH, Hur SA, Afshar T, Kolmert J, Zurita J, Wheelock CE, Carlsten C. Impact of Short-Term Diesel Exhaust Exposure on Prothrombotic Markers in Chronic Obstructive Pulmonary Disease: A Randomized, Double-Blind, Crossover Study. Ann Am Thorac Soc. 2024 Dec;21(12):1715-1722. doi: 10.1513/AnnalsATS.202311-955OC.
PubMed 39167788Yoon M, Ryu MH, Huff RD, Belvisi MG, Smith J, Carlsten C. Effect of traffic-related air pollution on cough in adults with polymorphisms in several cough-related genes. Respir Res. 2022 May 4;23(1):113. doi: 10.1186/s12931-022-02031-8.
PubMed 35509099Ryu MH, Afshar T, Li H, Wooding DJ, Orach J, Zhou JS, Murphy S, Lau KSK, Schwartz C, Yuen ACY, Rider CF, Carlsten C. Impact of Exposure to Diesel Exhaust on Inflammation Markers and Proteases in Former Smokers with Chronic Obstructive Pulmonary Disease: A Randomized, Double-blinded, Crossover Study. Am J Respir Crit Care Med. 2022 May 1;205(9):1046-1052. doi: 10.1164/rccm.202104-1079OC.
PubMed 35202552Syed N, Ryu MH, Dhillon S, Schaeffer MR, Ramsook AH, Leung JM, Ryerson CJ, Carlsten C, Guenette JA; Canadian Respiratory Research Network. Effects of Traffic-Related Air Pollution on Exercise Endurance, Dyspnea, and Cardiorespiratory Responses in Health and COPD: A Randomized, Placebo-Controlled, Crossover Trial. Chest. 2022 Mar;161(3):662-675. doi: 10.1016/j.chest.2021.10.020. Epub 2021 Oct 23.
PubMed 34699772Wooding DJ, Ryu MH, Li H, Alexis NE, Pena O, Carlsten C; Canadian Respiratory Research Network. Acute air pollution exposure alters neutrophils in never-smokers and at-risk humans. Eur Respir J. 2020 Apr 3;55(4):1901495. doi: 10.1183/13993003.01495-2019. Print 2020 Apr.
PubMed 31806722
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Traffic-Related Air Pollution on Smokers at Risk for Developing COPD
- ClinicalTrials.gov ID
- NCT02236039
- Acronym / sponsor ID
- COPA / H14-00821
- Conditions
- COPD
- Keywords
- Diesel exhaust, Air pollution, Airway responsivness
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- 27 Oct 2014 (actual)
- Primary completion
- 1 May 2019 (actual)
- Study completion
- 1 May 2019 (actual)
- First posted
- 10 Sep 2014 (estimated)
- 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.
The investigators are investigating the effects of traffic-related diesel exhaust on lung function and the immune system in those at risk for COPD. The individual will be exposed to either filtered air (FA) or carefully controlled levels of diesel exhaust (DE) in our exposure chamber. Post exposure the individual will complete a steady state exercise test. 24h later, a procedure called bronchoscopy (whereby a thin, flexible tube is placed down the throat and into the lungs) will be used so that samples can be collected from the lungs. After 1 month the entire procedure will be repeated with the alternative exposure.
Detailed description
- Purpose: To study the effects of traffic related diesel exhaust on people at risk for developing COPD.
- Hypotheses: Hypothesis 1: An increase in proteins, in the exposed lung and blood, that are associated with the pathophysiology of COPD. Hypothesis 2: Air trapping, dyspnea, and impaired exercise tolerance. Such increases will be more pronounced in those with COPD than in control subjects.
- Justification: The use of diesel engines is increasing because they are more fuel-efficient than gasoline engines. However, diesel engines produce different emissions than gasoline engines. Diesel exhaust is emitted from the tailpipe of both "on-road" diesel engine vehicles (diesel cars, buses and trucks) and "non-road" diesel engines (locomotives, marine vessels and some construction equipment). Diesel exhaust consists of both gaseous and particulate air pollutants. People with COPD may be sensitive to air pollution; we would like to know how diesel exhaust (DE) can affects the respiratory and immune systems. We are not expecting that responses will be noticeable to the participant; we are expecting that any responses that may occur will only be detectable through careful examination of cells and tissues (e.g., bronchoalveolar lavage (fluid from lungs), blood). Understanding these subtle changes will help us prevent health problems associated with air pollution in the future.
- Objectives To provide biological plausibility and deepen mechanistic understanding of the emerging epidemiology suggesting a strong role for air pollution in COPD.
- Research Methods:
This is a blinded crossover experiment between two conditions (300 µg/m³ diesel exhaust or filtered air), randomized and counter-balanced to order. Data collection for each condition will be separated by a 4-week washout period.
Prior to the exposure participants will: 1) complete some questionnaires, 2) undergo a set of lung function tests (breathing tests), 3) undergo an incremental exercise test and 4) receive a physical exam by the primary investigator. A small sample of blood and spirometry measurements will also be collected for analysis.
After the exposure another series of exercise and lung function tests will be performed. Blood, spirometry measurements, bronchoalveolar lavage (BAL), endobronchial brushings and biopsies will also be collected for examination of cellular, functional and immunological changes influencing the airways.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Filtered air | Active comparator | Procedure: BronchoscopyExposure for 2 hours to filtered air followed by a bronchoscopy 24 hours post exposure. |
| Diesel exhaust | Experimental | Procedure: BronchoscopyExposure for 2 hours to diesel exhaust followed by a bronchoscopy 24 hours post exposure. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age between 40-75 years of age
- Free of cardiovascular disease
- Free of insulin-dependent diabetes
- Study participants must agree to adhere to the following medication intake protocol 24 hours prior to study visits:
- Overall, we are looking for 15 healthy controls without a history of smoking; 20 individuals with a history of smoking, but who have been non-smokers for at least 6 months prior to study participation; and 15 mild-moderate COPD patients (GOLD I and GOLD II).
Key exclusion criteria (11 listed)
- Not between the ages of 40-65 years.
- Are pregnant, breast-feeding, or planning to get pregnant in the following 12 months.
- Are currently using inhaled corticosteroids.
- Are allergic to salbutamol, lidocaine, fentanyl or midazolam.
- Are currently participating in another study that involves taking medications.
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 |
|---|---|---|
| BronchoscopyBronchoscopy with biopsy sampling, brushings and bronchoalveolar lavage (BAL) 24 hours post exposure. | Procedure or surgery | Diesel exhaust, Filtered air |
Primary outcome
Cytokine pattern
Time frame: 24 hours
BAL, BW, and blood cytokines will be assessed at 24h using immunoassays
3 secondary outcomes
Gene expression
Time frame: 24 hours
Cardiopulmonary function
Time frame: 1.5 hours
Cell culture
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2021.
- Background: PubMed 16452593Behndig AF, Mudway IS, Brown JL, Stenfors N, Helleday R, Duggan ST, Wilson SJ, Boman C, Cassee FR, Frew AJ, Kelly FJ, Sandstrom T, Blomberg A. Airway antioxidant and inflammatory responses to diesel exhaust exposure in healthy humans. Eur Respir J. 2006 Feb;27(2):359-65. doi: 10.1183/09031936.06.00136904.
- Background: PubMed 20130146Hsia CC, Hyde DM, Ochs M, Weibel ER; ATS/ERS Joint Task Force on Quantitative Assessment of Lung Structure. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418. doi: 10.1164/rccm.200809-1522ST. No abstract available.
- BackgroundGan, W. Q., J. M. FitzGerald, et al. (2013).
- Background: PubMed 17765526Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet. 2007 Sep 1;370(9589):765-73. doi: 10.1016/S0140-6736(07)61380-4.
- Background: PubMed 8943829Rudell B, Ledin MC, Hammarstrom U, Stjernberg N, Lundback B, Sandstrom T. Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust. Occup Environ Med. 1996 Oct;53(10):658-62. doi: 10.1136/oem.53.10.658.
- BackgroundSchikowski, T., M. Adam, et al. (2014).
- BackgroundMcCreanor, J., P. Cullinan, et al. (2007).
- Derived from this study: PubMed 39167788Ryu MH, Hur SA, Afshar T, Kolmert J, Zurita J, Wheelock CE, Carlsten C. Impact of Short-Term Diesel Exhaust Exposure on Prothrombotic Markers in Chronic Obstructive Pulmonary Disease: A Randomized, Double-Blind, Crossover Study. Ann Am Thorac Soc. 2024 Dec;21(12):1715-1722. doi: 10.1513/AnnalsATS.202311-955OC.
- Derived from this study: PubMed 35509099Yoon M, Ryu MH, Huff RD, Belvisi MG, Smith J, Carlsten C. Effect of traffic-related air pollution on cough in adults with polymorphisms in several cough-related genes. Respir Res. 2022 May 4;23(1):113. doi: 10.1186/s12931-022-02031-8.
- Derived from this study: PubMed 35202552Ryu MH, Afshar T, Li H, Wooding DJ, Orach J, Zhou JS, Murphy S, Lau KSK, Schwartz C, Yuen ACY, Rider CF, Carlsten C. Impact of Exposure to Diesel Exhaust on Inflammation Markers and Proteases in Former Smokers with Chronic Obstructive Pulmonary Disease: A Randomized, Double-blinded, Crossover Study. Am J Respir Crit Care Med. 2022 May 1;205(9):1046-1052. doi: 10.1164/rccm.202104-1079OC.
- Derived from this study: PubMed 34699772Syed N, Ryu MH, Dhillon S, Schaeffer MR, Ramsook AH, Leung JM, Ryerson CJ, Carlsten C, Guenette JA; Canadian Respiratory Research Network. Effects of Traffic-Related Air Pollution on Exercise Endurance, Dyspnea, and Cardiorespiratory Responses in Health and COPD: A Randomized, Placebo-Controlled, Crossover Trial. Chest. 2022 Mar;161(3):662-675. doi: 10.1016/j.chest.2021.10.020. Epub 2021 Oct 23.
- Derived from this study: PubMed 31806722Wooding DJ, Ryu MH, Li H, Alexis NE, Pena O, Carlsten C; Canadian Respiratory Research Network. Acute air pollution exposure alters neutrophils in never-smokers and at-risk humans. Eur Respir J. 2020 Apr 3;55(4):1901495. doi: 10.1183/13993003.01495-2019. Print 2020 Apr.
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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.
Christopher Carlsten, MD, MPH principal investigator
University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bronchoscopy in people with COPD, run by University of British Columbia at 1 site in Canada.
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 10 inclusion and 11 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: finished, as of the sponsor's last update on 2 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cytokine pattern (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02236039, which also lists 12 linked publications.
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 2 Nov 2021.