Role of T-Cells in Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Observational

Summary: 
      This study will examine the movement of T cells (a type of white blood cell) from the blood
      to the lungs in patients with asthma after exposure to an allergen, such as cat dander or
      pollen. Asthma is in large part due to inflammation of the bronchi (the breathing tubes of
      the lungs), causing heat, swelling and redness. T cells play a major role in the inflammatory
      reaction. A better understanding of T cell migration to the lungs after allergen exposure may
      lead to improved therapies for asthma.

      Patients between 18 and 50 years of age with mild allergic asthma may be eligible for this
      study. In addition, patients and healthy normal volunteers between 18 and 65 years of age may
      participate in a sub-study (blood draw) of this protocol. Participants will undergo the
      following procedures:

      Visit 1 (screening visit)

        -  Blood tests for blood counts and HIV

        -  Urine pregnancy test for women of childbearing potential.

      Visit 2

        -  Physical examination and electrocardiogram (EKG)

        -  Prick skin testing - A drop of allergen extract is put on the skin and the underlying
           skin is scratched with a needle. A positive test resembles an insect bite and may itch.

        -  Intradermal skin tests - Increasing concentrations of a drop of diluted allergen are
           injected into the skin and the allergic response is monitored until a 5-mm swelling (1/4
           inch) swelling develops.

        -  Methacholine challenge - The subject has repeated pulmonary function (breathing) tests
           after breathing methacholine, a drug that temporarily (for 5 to 10 minutes) worsens
           asthma symptoms.

        -  Physician evaluation and repeat pulmonary function test

      Visit 3

      - Allergen bronchoprovocation - This test will be done in patients whose physical evaluation
      and breathing test permit them to continue with the study. A heparin lock (needle device that
      stays in a vein to allow multiple blood draws without repeated sticks) is placed. The subject
      breathes 5 breaths of allergen through a nebulizer (device that creates a mist), followed by
      a breathing test. This procedure will be repeated with increasingly higher allergen doses
      until lung function significantly declines or for a maximum of 6 doses. Subjects are
      monitored for 8 hours after the last dose. Blood samples of 50 ml each (3.5 tablespoons) are
      collected at 1, 3, 5 and 8 hours, and a physician evaluation is done at the end of the 8
      hours. Additional 50-mm blood samples are collected the following two mornings.

      Visit 4

        -  Physician evaluation, blood test for anemia and pulmonary function test

        -  Serial blood draws - 50 ml of blood will be drawn, followed by salt-water nebulization
           and another 50-ml blood draw after 1 hour. Additional 50-ml blood samples will be drawn
           7 hours later and then on the next two mornings.

      Participants in the sub-study portion of this protocol will undergo the screening blood test,
      prick skin testing, breathing test after methacholine inhalation and a 100 ml-blood draw.
      These tests will be done in three sessions.
    

Detailed description: 
      In the last 10 years it has become generally accepted that asthma is an inflammatory disease
      of the airways. T lymphocytes play a key role in regulating this inflammatory response,
      through the elaboration of cytokines such as IL-4, IL-5, and IFN-gamma. IL-5 is of particular
      interest because it is the major eosinophil survival factor in vivo. Eosinophils are felt to
      be the major effector cells in asthma, causing damage to various airway structures.

      The pulmonary late phase response, a worsening of airflow seen 4-8 hours after allergen
      inhalation, is associated with many of the inflammatory changes seen in chronic asthma.
      Current studies suggest that during the late phase response peripheral blood T cells traffic
      to the lungs and express cytokines, specifically IL-4 and IL-5.

      We propose to investigate this trafficking by determining the frequencies and phenotype of
      cells capable of producing the above cytokines in the peripheral blood in subjects with mild
      allergic asthma. These studies should lead to a clearer understanding of the cells and
      processes that lead to T cell trafficking to the lung and may yield a tool to evaluate the
      proposed anti-inflammatory therapies for asthma.
    

Keywords: Lymphocytes; Asthma; Cytokines; Interleukin-5; Late Phase Response