Study of the Inflammation and Airway Changes That Occur After Exposure to Allergen in Asthmatics
| Status: | Recruiting |
|---|---|
| Conditions: | Asthma |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 10/28/2018 |
| Start Date: | March 2015 |
| End Date: | July 2019 |
| Contact: | Bobby J Antalek, MS, MPH |
| Email: | bobby.antalek@ucsf.edu |
| Phone: | 415-502-2892 |
Mechanistic Study of Epithelial miRNAs and T-cell Recruitment Dynamics That Occur After Allergen Challenge in Patients With Asthma.
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.
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.
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
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