COPD Originates in Polluted Air

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.