Immune Interactions in Severe Asthma

Sponsor

University of Pittsburgh (Other)

Overall Status

Recruiting

CT.gov ID

NCT02566668

Collaborator

(none)

120

Enrollment

Location

126

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research study is being done to learn more about severe asthma by comparing people with severe asthma to those with milder forms of asthma and people without asthma, at baseline and over time. Individuals are being asked to join a research study to help understand the differences in the lungs and blood of participants with severe asthma compared to those with milder asthma and healthy individuals, as well as differences in overall health. Investigators also want to determine whether these differences predict asthma-related and biologic outcomes over 1 year of follow up.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Other: 1 year Observational Follow-up

Detailed Description

This study will obtain human lung samples by bronchoscopy from a range of asthmatics and healthy controls to address questions related to the mechanisms for the development of the complex immune processes observed in the lungs. Samples will be evaluated for Type-1, Type-2 and Interleukin-27 (IL-27) expression (and their downstream signatures). In addition, these samples will be evaluated for the presence or absence of Interleukin-10 (IL-10) as a counter regulatory pathway. These pathways will be directly evaluated in epithelial brushings and bronchoalveolar lavage (BAL) cells, as well as BAL fluid. Broad gene expression profiling (Ribonucleic acid (RNA)-sequencing) will also be performed to determine the range of immune-inflammatory markers present in these severe asthmatics. Investigators will specifically address the Signal Transducers and Activators of Transcription (STAT) signaling pathways, particularly STAT-1 and STAT-3 to determine the pattern of activation and downstream responses to develop new therapies. Additionally, in a subset, investigators will compare targeted and untargeted gene expression as obtained from bronchoscopic samples with expression obtained from clinically performed video assisted thoracoscopic (VATS) biopsies of very severe systemic corticosteroid dependent patients. The ultimate goal of this studies is to determine whether a predictive biomarker panel can be identified in the less invasive bronchoscopic samples which predict the findings seen on VATS biopsy.

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Immune Airway-Epithelial Interactions in Steroid-Refractory Severe Asthma

Actual Study Start Date :

Sep 1, 2015

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Asthmatic 1 year observational follow-up	Other: 1 year Observational Follow-up Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.
Non-Asthmatic 1 year observational follow-up	Other: 1 year Observational Follow-up Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.

Arm

Intervention/Treatment

Asthmatic

1 year observational follow-up

Other: 1 year Observational Follow-up

Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.

Non-Asthmatic

1 year observational follow-up

Other: 1 year Observational Follow-up

Approximately 12 months after research bronchoscopy, subjects will return for follow-up visit.

Outcome Measures

Primary Outcome Measures

Eotaxin-3 and IL-27 expression and their downstream signatures [1 Year]
Measure eotaxin-3 and IL-27 expression in bronchoalveolar lavage cells and epithelial cells.

Secondary Outcome Measures

Global gene expression in the airway epithelium and bronchoalveolar lavage cells using RNA-sequencing [1 Year]
Signal transducer and activator of transcription (STAT) signaling pathways [1 Year]
Pattern of activation and downstream responses
Targeted and untargeted gene expression as obtained from bronchoscopic samples [1 Year]
Compare with expression obtained from video assisted thoracoscopic (VATS) biopsies of systemic corticosteroid dependent patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

18-65 years of age
Non-smoker
Asthmatic subjects must also demonstrate forced expiratory volume in 1 second (FEV1) bronchodilator reversibility ≥12% or airway hyperresponsiveness reflected by a methacholine provocative concentration causing a 20% fall in FEV1 (PC20) ≤16 mg/mL (Historical methacholine data from previous National Institutes of Health (NIH) trial will be allowed)

Exclusion Criteria:

Greater than 10 pack year smoking history (none in the last year)
Vocal cord dysfunction, cystic fibrosis or chronic obstructive pulmonary disorder
Other lung disease, or any coronary artery disease, hypertension, diabetes or renal failure that is not well-controlled.

Healthy Controls only: Pre-bronchodilator FEV1/Forced vital capacity (FVC) <0.70 or an improvement in FEV1 of more than 12% following 4 puffs of albuterol.