Effects of Diesel Exhaust Followed by Administration of Nasal Spray Flu Vaccine on Individuals With & Without Allergies
Condition: Allergic Rhinitis
MeSH terms: Rhinitis; Rhinitis, Allergic
Study type: Interventional

Summary: 
      Allergic rhinitis (AR) is a condition that exists when an individual with a specific allergy
      reacts to that allergen resulting in a runny and/or stuffy nose, postnasal drip, and possible
      symptoms of sneezing, scratchy throat, itchy nose, ears or throat. When the allergic person
      is exposed to such an allergen, the body reacts with overproduction of certain chemicals
      which cause inflammation and subsequent symptoms of AR. These responses are related to the
      body's hyperreactive response to exposure to an otherwise harmless substance such as dust,
      ragweed, pollen, cat dander etc.

      There are data to suggest that air pollution resulting from diesel exhaust can increase the
      body's response to airway inflammation caused by virus.

      The purpose of this research study is to determine if individuals with AR have increased
      inflammatory responses to flu virus following exposure to diesel exhaust (DE) vs exposure to
      clean air compared to how individuals who do not have allergies respond to the same exposure
      conditions. The hypothesis for this study is that diesel exhaust exacerbates LAIV-induced
      allergic nasal inflammation, using controlled exposures in AR volunteers compared to
      non-allergic individuals
    

Detailed description: 
      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)
    

Intervention name(s): live attenuated influenza virus (LAIV) with clean air; LAIV and diesel exhaust particles
Intervention type(s): Other; Other
Intervention description(s): Allergic subjects will be exposed to air followed by administration of live attenuated influenza virus; subjects with allergic rhinitis will be exposed to diesel exhaust particles followed by LAIV
Other intervention name(s): FluMist; FLuMist
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Keywords: diesel exhaust particles; live attenuated influenza virus vaccine; flu vaccine