T Cell Effector and Regulatory Mechanisms in Asthma
Condition: Asthma; Allergies
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 1

Summary: 
      The specific hypothesis for this study is that there are fundamental differences in T
      effector and T regulatory cell responses in the lung to allergens in allergic asthma (AA)
      when compared to allergic nonasthmatics (ANA) that account for the difference in clinical
      responses. We will address this by comparing T cell responses in AA versus ANA subjects.
      These experiments will correlate T cell responses with measures of airway physiology using
      state-of-the art lung imaging and examine mechanisms controlling T cell activation in the
      airways of AA and the function of airway T regulatory cells during AA.
    

Detailed description: 
      Despite advances in medications, allergic diseases, including allergic asthma, continue to
      rise in prevalence. For this reason, there is a need for a better understanding of the
      mechanisms of allergic diseases and novel insights into modulating allergic inflammation.
      CD4+ Th2-type lymphocytes seems to be central to the pathogenesis of allergic disease, as the
      levels of these cells and Th2 cytokines (IL-4, IL-5 and IL-13) are elevated in the airways of
      allergic asthma patients. The unifying hypothesis of this project is that understanding the
      mechanisms that determine the critical balance of effector and regulatory allergen-specific T
      cell activity in asthma will lead to new approaches for inducing allergen-specific tolerance
      and new therapeutic strategies for asthma.
    

Intervention name(s): Bronchoscopy, Segmental Allergen Challenge and Broncheoalveolar Lavage; PET-CT imaging(13NN perfusion/ventilation, 18FDG inflammation, and CT imaging)
Intervention type(s): Biological; Procedure
Intervention description(s): On the day of the first bronchoscopy,BAL will first be performed in the lingula without instillation of diluent or allergen.Then, a 2-ml aliquot of isotonic diluent is instilled into the right upper lobe. Then, the procedure will be repeated in the right middle lobe with instillation of 2-ml of standardized cat or mite allergen solution.A "test dose" concentration of allergen is administered first consisting of 2 ml of allergen at 1/10th(Cat,D.farinae) or 1/30th(D. pteronyssinus) the threshold concentration.If on visual inspection through the bronchoscope, there is no evidence of mucosal inflammation after two minutes, a second segmental allergen challenge will be done in the right middle lobe using 2-ml of full-dose allergen at the threshold concentration(Cat,D.farinae) or 1/3th the threshold concentration(D.pteronyssinus).This dose will be predetermined by quantitative skin prick testing.A second bronchoscopy is performed 24 hours after delivery of allergen extract and diluent.; Imaging is first performed the evening prior to the 1st bronchoscopy.An IV catheter is placed.An attenuation correction is performed to remove image distortion using a chest CT volumetric scan.Subjects are instructed to exhale to the same mean lung volume of the CT scan and hold their breath for 20sec.Simultaneous with apnea,13NNsaline is injected IV and a series of PET scans is acquired.Then subjects resume breathing, matching their previous respiratory rate and tidal volume.After 3 min,within an interval of 1 min,spirometry and 2 deep inhalations are performed,followed by 1 min of washout. For the second imaging visit, which will occur 24 hour later, the imaging sequence will be repeated as described above, but will also include 18FDG infusion.At least 30 minutes after the 13NN injection,10mCi of 18FDG is infused. Then, images are collected over a 75 minutes.Venous blood is sampled at 5 different time points over a 40-45 minute time window to determine plasma radioactive levels.
Other intervention name(s): One of 3 Standardized allergen extracts will be used:; 1)Cat hair; 2)Dust Mite Dermatophagoides farinae; 3)Dust Mite Dermatophagoides pteronyssinus; Phenolized saline diluent will also be used in this study.; All will be purchased from Greer Laboratories, Lenoir, NC.; 13N-N2 saline; 18F-FDG, 0.019 mSv/MBq
Intervention MeSH terms: Fluorodeoxyglucose F18
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Asthma; Allergic; Inflammation; Constriction; Airway; Challenge; Chemokines