COPD Originates in Polluted Air
Condition: COPD
Study type: Interventional

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.
    

Detailed description: 
      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.
    

Intervention name(s): Bronchoscopy
Intervention type(s): Procedure
Intervention description(s): Bronchoscopy with biopsy sampling, brushings and bronchoalveolar lavage (BAL) 24 hours post exposure.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Diesel exhaust; Air pollution; Airway responsivness