Effects of Co-Exposure to Air Pollution and Allergen

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.

Purpose/Objective: To study the effects of diesel exhaust particles on lung function and on allergic responses. 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. 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. 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

BAL IgE specific to the allergen used for allergen challenge will be assessed at 48 hrs, from the BAL, using immunocap assay

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.

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.

Determine if airway reactivity (measured by PC20 methacholine challenge) is augmented by DE (300 µg/m3 inhaled for two hours) exposure.

Inclusion Criteria: Age between 19 and 49 years. Non-smoking. Positive skin prick test for at least one of: birch, grass, or dust Exclusion Criteria: Using inhaled corticosteroids Pregnant or planning to be pregnant in the next 12 months / Breastfeeding Usage of bronchodilators more than three times per week. Co-morbidities (as assessed by the primary investigator) Taking part in other studies Unwilling to withhold bronchodilator, aspirin, anti-coagulant, antihistamine or decongestant medications or caffeine prior to testing procedures. FEV1(Forced expiratory volume in one second) < 70% predicted. Allergy to lidocaine, fentanyl, midazolam or salbutamol. Unstable asthma (i.e exacerbation in 2 weeks preceding testing)

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