Study of the Inflammation and Airway Changes That Occur After Exposure to Allergen in Asthmatics
Condition: Asthma
MeSH terms: Asthma
Intervention: Segmental airway allergen challenge; Bronchoscopy; Methacholine challenge test; Spirometry; Allergen skin prick test
Intervention MeSH terms: Methacholine Chloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Intervention model description: Single group before and after administration of allergen
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Asthma; Allergen challenge

Summary:

      This protocol describes a single site mechanistic study to investigate microRNAs (miRNAs)
      that are differentially expressed in the airway epithelium of patients with asthma at
      baseline and in response to allergen challenge. We hypothesize that allergen exposure
      enhances airway smooth muscle contractility and epithelial cell mRNA/miRNA production as a
      consequence of locally increased T-cell derived cytokine production. The study will involve
      three visits over the course of approximately 14 days. At Visit 1, participants will be
      characterized in detail with lung function testing, methacholine challenge testing, and
      allergen skin prick testing. At Visit 2, participants will undergo bronchoscopy with
      segmental allergen administration of either cat or dust mite standardized allergen extract.
      At Visit 3 (either 24 hours later or 7 days later), bronchoscopy will be performed to collect
      airway samples including bronchoalveolar lavage (BAL), epithelial brushings and endobronchial
      biopsies. Sample analysis will include measurement of miRNA and mRNA expression in epithelial
      brushings (RNAseq and qPCR); analysis of cell surface markers on BAL cells and blood cells;
      and collection of endobronchial biopsies for immunostaining of immune cells localization,
      immunoblotting of smooth cell protein phosphorylation, analysis of mucin content and smooth
      muscle cell subculture. A total of 38 subjects (26 asthmatics with stable or well-controlled
      asthma, 6 allergic non-asthmatics and 6 non-allergic non-asthmatics) will complete the study.
    

Eligibility criteria:

        Allergic/Non-Asthmatic subjects and Allergic/Asthmatic subjects

        Inclusion Criteria:

          -  Positive skin test to dust mite or cat allergen

        Non-Allergic/Non-Asthmatic subjects

        Inclusion Criteria:

          -  Negative skin test to panel of 12 allergens, including dust mite and cat allergen

        All groups

        Exclusion Criteria:

          -  History of intubation for asthma exacerbation

          -  Use of Xolair (omalizumab) within the last 6 months

          -  Immunotherapy with cat or dust mite extract now or in the past 5 years

          -  ≥ 10 pack-years smoking or any smoking in the past year

          -  Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection

          -  History of dermatographia

          -  History of anaphylaxis to cat allergen

          -  Participation in another research study involving a drug or biologic during the past
             30 days

          -  Presence of past or current medical problems/other factors that may pose additional
             risks from participation or influence study results, as determined per study
             investigator