Air Pollution and Allergens - Attenuation of Health Effects Particle Reduction
Condition: Allergies
MeSH terms: Hypersensitivity
Study type: Interventional

Summary: 
      The study probes the effects of combined exposures to diesel exhaust and allergens on lung
      function and on the immune system, specifically focusing on the ability of a particle
      depletion technique to attenuate effects we and others have seen previously. Individuals are
      exposed to either filtered air (FA), carefully controlled levels of diesel exhaust (DE) or
      particle-depleted diesel exhaust (PDDE) in our exposure chamber, after which the
      investigators will administer an inhaled allergen challenge. 48h later, a procedure called
      bronchoscopy is used to collect samples from the lungs. After 1 month, the entire procedure
      is to be repeated with one of the alternate exposures. This will be repeated 4 times (4
      exposures; 2 filtered air, 1 diesel exhaust, 1 particle-depleted diesel exhaust)
    

Detailed description: 
      1. Purpose/Objective:

           The aim of this study is to investigate the ability of depletion of diesel exhaust
           particles to attenuate adverse effects of diesel exhaust on lung function and on
           allergic responses.

        2. Hypotheses:

           Hypothesis 1: Allergen-specific immune response (specific IgG4, etc; relevant responses
           in DNA methylation and proteomics) in allergen-challenged airways in sensitized
           individuals is increased by diesel exhaust "synergy".

           Hypothesis 2: Synergistic responses will be greater in asthmatics than in
           non-asthmatics.

           Hypotheses 3: Synergy is attributable to the particulate fraction of DE (i.e. is
           normalized by particle depletion).

        3. Justification:

           Diesel exhaust consists of both gaseous and particulate air pollutants. In recent
           studies, cardiovascular effects seem attenuated when the particulate portion is removed.
           We would like to know if that is true for respiratory and immunological endpoints.
           Understanding these changes may help us prevent health problems associated with air
           pollution in the future.

        4. Research Method:

      Blinded crossover experiment between four conditions (DE and allergen, PDDE and allergen, FA
      and allergen, FA and saline), randomized and counter-balanced to order. Each condition will
      be separated by a 4-week washout period.

      An inhaled allergen or saline challenge is delivered after each exposure (DE, PDDE, or FA).
      24 h post challenge, airway reactivity will be assessed with a methacholine challenge. 48 h
      post challenge, bronchoalveolar lavage (BAL), airway brushes and tissue biopsies will be
      obtained for analysis of immune activation. Nasal lavage samples will also be collected to
      examine responses in the upper airways and blood and urine will be studied to examine
      systemic responses. Spirometry and methacholine challenge will be used to assess effects on
      airway function.
    

Intervention name(s): Allergen; Saline; Particle depleted diesel exhaust
Intervention type(s): Other; Other; Other
Intervention description(s): Subject specific allergen is inhaled on day 1 of the triad; Saline is inhaled on day 1 of the triad; High-efficiency particulate filtration of diesel exhaust
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Diesel exhaust; Particle depleted diesel exhaust; Air pollution; Airway responsiveness; Allergies