A Study of Inhalation of 20,000 EU CCRE in Normal Volunteers Compared to Allergic Asthmatic Individuals
Condition: Asthma; Hypersensitivity
MeSH terms: Asthma; Hypersensitivity
Study type: Interventional
Phase: Phase 1

Summary: 
      This will be a single center, open label study comparing baseline characteristics of
      recovered sputum cells (collected on screening day) to those of cells recovered 6 hours after
      inhalational challenge with 20,000 EU Clinical Center Reference Endotoxin (CCRE, a component
      of air pollution)) within each group as well as cross group comparisons between individuals
      with allergic asthma (AA's)and normal volunteers (NV's). The primary objective of this study
      is to test the hypothesis that persons with allergic asthma will have an increased neutrophil
      response to challenge with 20,000 EU CCRE compared to normal volunteers. Secondary objectives
      include post CCRE comparison between AA's and NV's with regard to changes in airway cells and
      blood as well as changes in mucociliary clearance (MCC) in response to inhalation of 20,000
      EU CCRE.
    

Detailed description: 
      This will be a single center, open label study of allergic asthmatic and normal volunteers.
      The protocol will compare baseline characteristics of recovered sputum cells (collected on
      screening day) to those of cells recovered 6 hours after inhalational challenge with CCRE
      within each group as well as cross group comparisons between AA's and NV's. The following
      information indicates procedures to be performed at each visit as well as the anticipated
      duration of visits. Subsequent to this description are details regarding specific study
      procedures.

      Visit 1: Baseline Visit (5 hours)

        1. Consent will be obtained, review of subject's medical history, current medications and
           inclusion/exclusion criteria.

        2. Vital sign measurements (temperature, pulse, respiratory rate, blood pressure), oxygen
           saturation, and symptom scoring

        3. Urine pregnancy test for women of child bearing potential

        4. Spirometry

        5. Venipuncture for CBC with differential and baseline blood analyses

        6. Physical exam of the ears, nose, throat and chest

        7. Collection of exhaled breath for measurement of nitric oxide level

        8. Xenon equilibrium gas scan and MCC

        9. MCC scan

       10. Sputum induction

       11. After completion of the sputum induction, subjects will have brief MCC scan (< 10
           minutes)

      Visit 2: 24 hours post baseline subjects will return for the following 1 hour visit:

        1. Review any change in medical status over prior 24 hours, vital signs, O2 saturation and
           symptom score

        2. Follow up MCC scan

      Visit 3: 24-48 hours prior to challenge visit at least 2 days after the baseline visit (½
      hour)

        1. Review change in medical status since last visit; vital signs, oxygen saturation, &
           symptom score

        2. Urine pregnancy test

        3. Spirometry

      Visit 4: Endotoxin (CCRE) challenge day (8.5 to 9 hours)

        1. Review any change in medical status since last visit

        2. Vital signs, oxygen saturation, and symptom score

        3. Spirometry

        4. Physical exam of the ears, nose, throat and chest

        5. If above measures are acceptable, CCRE challenge will be performed

        6. Post-challenge monitoring including spirometry, vital signs, oxygen saturation, and
           symptom score at the following intervals post challenge: 30 and 60 minutes and then
           hourly for 5 additional hours.

        7. Post challenge venipuncture (blood draw) for CBC with differential and post CCRE blood
           analyses

        8. Collection of exhaled breath for measurement of nitric oxide level.

        9. Four hours post challenge, subject will have MCC evaluated

       10. After MCC is assessed, sputum induction will be performed.

       11. After completion of the sputum induction, subjects will have brief MCC scan (< 10
           minutes)

       12. Discharge home or, alternatively, to GCRC for overnight observation per study MD.

      Visit 5: 24 hours post challenge visit (1 hour)

        1. Subject returns to the CEMALB, vital signs, oxygen saturation, and symptom score

        2. Collection of exhaled breath for measurement of nitric oxide level.

        3. Spirometry

        4. Follow-up MCC scan

        5. Each volunteer will be given a symptom scoring sheet for each day up to 96 hours (4
           days) after challenge (see accompanying symptom scoring sheet in Appendix 3).

      Post Challenge Observations/Reporting (5 minutes)

      1. Subjects will be contacted for phone call follow-up 48-96 hours after challenge (see
      script Appendix 4 of accompanying protocol)

      Study discontinuation visit within 10 days of the challenge dose: (15 minutes)

        1. Vital signs, O2 saturation, symptom score, spirometry

        2. If any findings are abnormal, medical evaluation as directed by the study physician will
           be undertaken Appendix 1 of the accompanying protocol provides a summary table regarding
           procedures performed at each subject study visit
    

Intervention name(s): Clinical Center Reference Endotoxin (CCRE); Clinical Center Reference Endotoxin (CCRE)
Intervention type(s): Biological; Biological
Intervention description(s): inhalation challenge with 20,000 EU CCRE; inhalation of 20,000 EU CCRE
Other intervention name(s): air pollution; air pollution
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: normal volunteer; healthy control volunteer; healthy subjects; asthma; allergy; allergic asthma