COPD Originates in Polluted Air

NCT ID: NCT02236039

Last Updated: 2021-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-27

Study Completion Date

2019-05-01

Brief Summary

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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

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1. Purpose:

To study the effects of traffic related diesel exhaust on people at risk for developing COPD.
2. 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.
3. 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.
4. Objectives To provide biological plausibility and deepen mechanistic understanding of the emerging epidemiology suggesting a strong role for air pollution in COPD.
5. 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

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COPD

Keywords

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Diesel exhaust Air pollution Airway responsivness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Filtered air

Exposure for 2 hours to filtered air followed by a bronchoscopy 24 hours post exposure.

Group Type ACTIVE_COMPARATOR

Bronchoscopy

Intervention Type PROCEDURE

Bronchoscopy with biopsy sampling, brushings and bronchoalveolar lavage (BAL) 24 hours post exposure.

Diesel exhaust

Exposure for 2 hours to diesel exhaust followed by a bronchoscopy 24 hours post exposure.

Group Type EXPERIMENTAL

Bronchoscopy

Intervention Type PROCEDURE

Bronchoscopy with biopsy sampling, brushings and bronchoalveolar lavage (BAL) 24 hours post exposure.

Interventions

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Bronchoscopy

Bronchoscopy with biopsy sampling, brushings and bronchoalveolar lavage (BAL) 24 hours post exposure.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Age between 40-75 years of age
2. Free of cardiovascular disease
3. Free of insulin-dependent diabetes
4. 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
* 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).

Exclusion Criteria

* 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.
* 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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of British Columbia

OTHER

Sponsor Role lead

Responsible Party

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Christopher Carlsten

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Christopher Carlsten, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

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University of British Columbia

Vancouver, British Columbia, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 16452593 (View on PubMed)

Hsia 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.

Reference Type BACKGROUND
PMID: 20130146 (View on PubMed)

Gan, W. Q., J. M. FitzGerald, et al. (2013).

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 17765526 (View on PubMed)

Rudell 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.

Reference Type BACKGROUND
PMID: 8943829 (View on PubMed)

Schikowski, T., M. Adam, et al. (2014).

Reference Type BACKGROUND

McCreanor, J., P. Cullinan, et al. (2007).

Reference Type BACKGROUND

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.

Reference Type DERIVED
PMID: 39167788 (View on PubMed)

Yoon 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.

Reference Type DERIVED
PMID: 35509099 (View on PubMed)

Ryu 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.

Reference Type DERIVED
PMID: 35202552 (View on PubMed)

Syed 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.

Reference Type DERIVED
PMID: 34699772 (View on PubMed)

Wooding 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.

Reference Type DERIVED
PMID: 31806722 (View on PubMed)

Other Identifiers

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H14-00821

Identifier Type: -

Identifier Source: org_study_id