Screening day: This visit will occur approximately 2-4 weeks before your exposure day. You will come to the research facility where you will discuss this consent form with the study coordinator and complete the signature areas. Your vital signs (pulse, temperature, BP, oxygenation saturation) will be measured and the following evaluations will be performed:
* For females of child bearing potential, a urine pregnancy test
* Review your medical history and any recent health changes
* Completion of a questionnaire regarding your allergy symptoms
* Collection of spirometric (pulmonary function testing) data will be performed. You must demonstrate normal pulmonary function in order to continue in the study. You will be asked to inhale as deeply as possible, then exhale as rapidly and completely as possible into a mouthpiece which is connected to a computer which measures various lung volumes and which will tell us if your lung function is normal.
* Blood draw from a hand or arm vein to test for HIV and recent influenza exposure, as well as serum markers, T cell stimulation and WBC characterization. The volume of blood will be up to 50 cc (approximately 3 tablespoons).
* A buccal swab will be performed for genotyping which entails rubbing a toothbrush on the inside of your cheeks to loosen the cells followed by repeating the rubbing in the same place with a soft swab (similar to a Q tip® with a longer stick).
* Physical examination by a study physician
* Allergy skin test if this has not been performed during the previous 2 years
* Collection of nasal lavage fluid which will involve spraying some salt water into your nose repeatedly and then blowing your nose into a cup
* Nasal biopsy during which the researcher gently scrapes the inside lining of your nose with a plastic stick
Day 0 (Monday): You will be asked to eat a light breakfast and arrive at the EPA in early to mid morning. You will need to wear comfortable clothes and shoes, and bring a lunch.
* Collection of vital sign measurements and update in medical condition as well as medications taken since the previous visit
* Urine pregnancy test, if applicable
* A telemetry monitor will be placed so that your heart rhythm can be monitored during your chamber exposure. This will include having monitor wires attached to your chest and shoulders with an adhesive pad. The other end of the wires is connected to a box that can be tied to your waste and which will transmit your heart rhythm to a screen so we can observe it
* Spirometry measurements: This test measures the volume of air that can be exhaled and the rate of airflow during exhalation after a maximal inhalation. You will inhale as deeply as possible, then exhale as rapidly and completely as possible into the spirometer. Measurements obtained from each maneuver include the forced vital capacity (FVC), the forced expiratory volume in the first second (FEV1), the maximal mid-expiratory flow rate (FEF 25-75%) and the peak flow (PF). The largest FVC and FEV1, from at least 3 acceptable trials, are selected for analysis; the flow rates are selected from the trial with the largest sum of FVC.
* Nasal lavage
* You will have a 2 hour exposure to either diesel particles or air. The type of exposure you will receive will be randomized, meaning that you will be assigned to the air or diesel exposure group by chance, like flipping a coin. The exposure will be double blind which means that neither you nor the study investigators and staff will know whether you are being exposed to diesel exhaust or air except in the event of any emergency when this information could be revealed. If you are randomized to receive a diesel exposure, the diesel will be generated from an engine mounted on a vehicle located outside of the EPA Human studies Facility (HSF). The diesel exhaust (DE) is then introduced into the exposure chamber after dilution with clean filtered and humidified air by approximately 1/30th to give a chamber concentration of approximately 100 μg/m3. The amount of DE used for exposure in this study would be equivalent to concentrations encountered at busy intersections in large urban areas. DE concentrations proposed are below occupational levels for some truck drivers (generally about 100-300 µg/m3) and 1-2 mg/m3 for some mines. Some areas of heavily trafficked streets in Los Angeles and New York City have had DE levels \> 20 µg/m3, and nearby residents could have exposure to these concentrations over several hours. If you are randomized to clean air, you will receive Chapel Hill air which has been filtered to remove ambient air pollutants
* After your exposure you will have additional spirometry testing and return to the medical station where you will be monitored for 3 hours. You will also have time to eat your lunch which we are requesting that you bring with you from home
* Both before and after your exposure, the level of carbon monoxide in your blood will be tested
* Three hours after your exposure is complete, the FluMist® vaccine will be administered by spraying the vaccine once into each nostril. Shortly after that you will be discharged home
Days 1-3 (Tuesday-Thursday). Each day, the following will be obtained:
* Vital signs and update any changes in medical condition
* Nasal lavage
Day 4 (Friday):
* Vital signs and medical update
* Nasal lavage
* Nasal biopsy
* Blood draw - serum markers, WBC characterization. The volume of blood will be up to 50cc (approximately 3 tablespoons)
Day 9 +/- 1 day (one visit sometime between the Tuesday through Thursday after the week you have received the FluMist®):
* Vital signs and health update
* Nasal lavage
Day 21 +/-7 days after the FluMist dose
* Vital signs and health update
* Urine pregnancy test, if applicable
* Blood draw to check your post -vaccine anti-influenza titer, as well as serum markers, T cell stimulation and WBC characterization. The volume of blood will be up to 50 cc (approximately 3 tablespoons)