Effects of Co-Exposure to Air Pollution and Allergen
Condition: Allergies
MeSH terms: Hypersensitivity
Study type: Interventional

Summary: 
      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.
    

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
    

Intervention name(s): Allergen; Saline
Intervention type(s): Other; Other
Intervention description(s): Subject specific allergen is placed in the lungs on day 1 of each triad; Saline will be placed in the lung on day 1 of each triad
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Diesel exhaust; Air pollution; Airway responsiveness; Allergies