Clinical trial NCT02566668: Immune Interactions in Severe Asthma
Official title: Immune Airway-Epithelial Interactions in Steroid-Refractory Severe Asthma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Asthma
Keywords: Asthma
Severe Asthma
IL-10
IL-27
IL-13
Epithelial Cells
T lymphocytes
Interferon-g
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2015-10-02
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be selected using a Research Registry and clinic patients of the Investigators.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Eotaxin-3 and IL-27 expression and their downstream signatures
timeFrame: 1 Year
Secondary outcomes:
measure: Global gene expression in the airway epithelium and bronchoalveolar lavage cells using RNA-sequencing
timeFrame: 1 Year
measure: Signal transducer and activator of transcription (STAT) signaling pathways
timeFrame: 1 Year
measure: Targeted and untargeted gene expression as obtained from bronchoscopic samples
timeFrame: 1 Year
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Asthma Institute at UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Sally E Wenzel, MD
role: PRINCIPAL_INVESTIGATOR
References: