Cell Biology of Steroid Resistant Asthma
The hypothesis is that patients who demonstrate steroid resistant asthma by showing little or no improvement in lung function after a course of oral steroids have different cellular responses to steroids than patients who are steroid sensitive. These altered responses are the reason they demonstrate steroid resistance.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Investigating Biomarkers of Steroid Resistant Asthma|
- Assess the prevalence of steroid resistance and to determine what fraction of steroid resistant subjects have positive skin tests and IgE levels ≥30 IU/ml
- Assess whether DEX-induced MKP-1 mRNA levels are decreased in PBMC or whole blood cells of SR, as compared to SS, asthmatics
- Determine whether T cells from SR vs SS asthmatics proliferate in the presence of increasing concentrations of DEX
- Determine whether DEX inhibits IL-6, TNF alpha, and IL-13 secretion in PBMC of SR, as compared to SS, asthmatics
- Examine expression of GCR-beta and GCR alpha mRNA in PBMC of SR, as compared to SS, asthmatics, T
- Analyze PBMC isolated from heparinized blood stored for 18 hours overnight at room temperature for specific aims A through D.
|Study Start Date:||August 2006|
|Study Completion Date:||March 2007|
Current NHLBI guidelines for persistent asthma management recommends the use of steroids for treatment of airway inflammation (1,2). However, some asthmatics do not respond to steroids (3-6). Unfortunately these patients are subjected to the unwanted side effects (osteoporosis, cataracts, etc) of high dose steroid therapy because non-immune tissues remain sensitive to steroids. Recent studies suggest that the costs of asthma are largely attributable to uncontrolled disease (7). Thus, it is important to understand the mechanism(s) of steroid resistance and introduce new forms of therapy for the treatment of these difficult to control asthmatics. As a prelude to pharmaceutical studies in steroid resistant asthma, it is imperative to develop biomarkers that can robustly identify individuals likely to be poor steroid responders so that alternative non-steroid anti-inflammatory therapies, such as Xolair®, can be introduced early in the course of asthma therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00361920
|United States, Colorado|
|National Jewish Medical and Research Center|
|Denver, Colorado, United States, 80206|
|Principal Investigator:||Donald Leung, MD,PhD||National Jewish Health|