Effects of Co-Exposure to Air Pollution and Allergen

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of British Columbia
ClinicalTrials.gov Identifier:
NCT01792232
First received: November 14, 2012
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

The investigators are investigating the effects of combined exposures to diesel exhaust and allergens on lung function and on the immune system. After exposing individuals to either filtered air or carefully controlled levels of diesel exhaust in our exposure chamber, The investigators will use a procedure called bronchoscopy (whereby a thin, flexible tube is passed down the throat and into the lungs) to place a small amount of allergen directly in the lung. 48h later, the bronchoscopy will be repeated so that samples can be collected from the lungs. After 1mo, the entire procedure will be repeated with the alternate exposure.


Condition Intervention
Allergies
Other: Allergen
Other: Saline

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Exposure to Allergens and Air Pollution on Lung Function and Immunity

Resource links provided by NLM:


Further study details as provided by University of British Columbia:

Primary Outcome Measures:
  • Allergen-specific IgE [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    BAL IgE specific to the allergen used for allergen challenge will be assessed at 48 hrs, from the BAL, using immunocap assay


Secondary Outcome Measures:
  • Human immune response [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Determine if allergen-induced eosinophilic activation (measured by flow cytometry) and a Th2-type cytokine pattern is augmented by DE (300 µg/m3 inhaled for two hours) exposure.

  • Oxidative stress [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Establish that bronchial segment allergen-induced oxidative stress (urine 8-isoprostane, measured by ELISA) is augmented by DE (300 µg/m3 inhaled for two hours) exposure.

  • Airway reactivity [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Determine if airway reactivity (measured by PC20 methacholine challenge) is augmented by DE (300 µg/m3 inhaled for two hours) exposure.


Enrollment: 18
Study Start Date: October 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Filtered air
Exposure for 2 hours to filtered air followed by subject specific allergen placed in lung
Other: Allergen
Subject specific allergen is placed in the lungs on day 1 of each triad
Experimental: Diesel exhaust
Exposure for 2 hours to diesel exhaust followed by subject specific allergen placed in lung
Other: Allergen
Subject specific allergen is placed in the lungs on day 1 of each triad
Active Comparator: Filtered air control
Exposure for 2 hours to filtered air followed by subject saline placed in lung
Other: Saline
Saline will be placed in the lung on day 1 of each triad
Active Comparator: Diesel exhaust control
Exposure for 2 hours to diesel exhaust followed by saline placed in lung
Other: Saline
Saline will be placed in the lung on day 1 of each triad

Detailed Description:
  1. Purpose/Objective:

    To study the effects of diesel exhaust particles on lung function and on allergic responses.

  2. Hypotheses:

    Hypothesis 1: DE exposure augments systemic oxidative stress from allergen challenge in allergen-sensitized individuals.

    Hypothesis 2: DE exposure augments allergen-specific immune response in allergen-challenged airways in sensitized individuals. These responses will be greater in asthmatic individuals than in non-asthmatics.

  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. Since people with asthma and allergic diseases appear to be sensitive to air pollution, we would like to know how diesel exhaust (DE) can affects your respiratory and immune systems. 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 your lungs), blood, urine). Understanding these potentially subtle changes will help us prevent health problems associated with air pollution in the future.

  4. Research Method:

This is a blinded crossover experiment between two conditions (DE or filtered air, FA), randomized and counter-balanced to order. Data collection for each condition will be separated by a 4-week washout period.

Following each exposure, The investigators will use bronchoscopy (performed at the Vancouver General Hospital Endoscopy Suite) to deliver a diluent-controlled segmental allergen challenge (SAC). 24 h post-SAC, airway reactivity will be assessed with a methacholine challenge. 48 h post-SAC, bronchoalveolar lavage (BAL), airway brushes and tissue biopsies will be obtained in the same regions for analysis of immune activation. Nasal lavage samples will also be collected to examine responses in the upper airways and blood and urine will be studied to examine systemic responses. Spirometry and methacholine challenge will be used to assess effects on airway function

  Eligibility

Ages Eligible for Study:   19 Years to 49 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age between 19 and 49 years.
  2. Non-smoking.
  3. Positive skin prick test for at least one of: birch, grass, or dust

Exclusion Criteria:

  1. Using inhaled corticosteroids
  2. Pregnant or planning to be pregnant in the next 12 months / Breastfeeding
  3. Usage of bronchodilators more than three times per week.
  4. Co-morbidities (as assessed by the primary investigator)
  5. Taking part in other studies
  6. Unwilling to withhold bronchodilator, aspirin, anti-coagulant, antihistamine or decongestant medications or caffeine prior to testing procedures.
  7. FEV1(Forced expiratory volume in one second) < 70% predicted.
  8. Allergy to lidocaine, fentanyl, midazolam or salbutamol.
  9. Unstable asthma (i.e exacerbation in 2 weeks preceding testing)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01792232

Locations
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V5Z 1M9
Sponsors and Collaborators
University of British Columbia
Investigators
Principal Investigator: Christopher Carlsten, MD, MPH University of British Columbia
  More Information

Publications:

Responsible Party: University of British Columbia
ClinicalTrials.gov Identifier: NCT01792232     History of Changes
Other Study ID Numbers: H11-01831
Study First Received: November 14, 2012
Last Updated: December 16, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of British Columbia:
Diesel exhaust
Air pollution
Airway responsiveness
Allergies

Additional relevant MeSH terms:
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on July 20, 2014