COPD Originates in Polluted Air

NCT02236039 | Completed

• 1 other identifier: H14-00821
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

COPD

Keywords

Diesel exhaust; Air pollution; Airway responsivness

Outcome Measures

Primary Outcomes (1)

• Cytokine pattern

  BAL, BW, and blood cytokines will be assessed at 24h using immunoassays

  24 hours

Secondary Outcomes (3)

• Gene expression

  24 hours

• Cardiopulmonary function

  1.5 hours

• Cell culture

  24 hours

Study Arms (2)

Filtered air

ACTIVE COMPARATOR

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

Procedure: Bronchoscopy

Diesel exhaust

EXPERIMENTAL

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

Procedure: Bronchoscopy

Interventions

Bronchoscopy PROCEDURE

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

Diesel exhaust; Filtered air

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (12)

• 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.

  PMID: 16452593 BACKGROUND

• 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.

  PMID: 20130146 BACKGROUND

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

  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.

  PMID: 17765526 BACKGROUND

• 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.

  PMID: 8943829 BACKGROUND

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

  BACKGROUND

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

  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.

  PMID: 39167788 DERIVED

• 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.

  PMID: 35509099 DERIVED

• 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.

  PMID: 35202552 DERIVED

• 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.

  PMID: 34699772 DERIVED

• 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.

  PMID: 31806722 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• Christopher Carlsten, MD, MPH

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 11, 2014
• First Posted: September 10, 2014
• Study Start: October 27, 2014
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: November 2, 2021

Record last verified: 2021-10

Locations

CA (1)