Inflammatory Processes in the Airway of Asthmatics With Persistent Bronchial Hyperreactivity
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||Mechanisms of Airway Inflammation: Natural Exacerbation of Asthma Induced by Glucocorticoid Withdrawal|
- change in CD3 positive T cells in the airway submucosa [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
- inflammatory cell markers in the airway (CD4, CD8, CD68, CD45, EG2/MBP, tryptase, and neutrophil elastase) [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
- RANTES expression in airway [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
- FEV1, peak expiratory flows [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
- methacholine PC20 [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
- asthma symptom score [ Time Frame: Measured at Week 4 ] [ Designated as safety issue: No ]
|Study Start Date:||September 2001|
|Study Completion Date:||February 2011|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
Open label inhaled fluticasone
Patients are treated with open label high dose fluticasone for 30 days then discontinued. Comparisons are pre- and post- treatment single arm.
The Inhaled Glucocorticoid Withdrawal Protocol will investigate abnormalities in the asthmatic airway that occur in the setting of a "natural" endogenous exacerbation. It is known that chronic treatment with inhaled glucocorticoids causes a nearly complete disappearance of inflammatory cells from the airway and improvement in bronchial hyperreactivity, yet such patients have persistent bronchial hyperreactivity. Withdrawal of inhaled glucocorticoids causes a worsening of bronchial hyperreactivity. These observations suggest that a chronic derangement in the asthmatic airway might exist, which is unmasked by withdrawal of inhaled glucocorticoids and which reinitiates the inflammatory process. These "persistent" abnormalities in the asthmatic airway may be seen during quiescent stages of chronic asthma even when airway inflammatory changes are not evident. The abnormalities may be seen during the period of treatment with inhaled glucocorticoids or they may appear as one of the first signs after the withdrawal of inhaled glucocorticoids, thereby initiating the recurrence of asthma and promoting inflammation.
The purpose of this study is to examine inflammatory processes in the airway of moderate to severe persistent asthmatics who have persistent bronchial hyperreactivity despite chronic administration of inhaled glucocorticoids. Each participant will undergo bronchoscopic procedures and have assessment of bronchial hyperreactivity at the following two time points: 1) during treatment with inhaled fluticasone; and 2) after acute withdrawal of inhaled fluticasone.
The primary outcome of this study is the change in CD3 positive T cells in the airway submucosa.
The key secondary outcomes are as follows: 1) other inflammatory cell markers in the airway (e.g., CD4, CD8, CD68, CD45, EG2/MBP, tryptase, and neutrophil elastase); 2) RANTES (regulated on activation, normal T expressed and secreted) expression in airway; 3) FEV1 peak expiratory flows; 4) methacholine PC20; and 5) asthma symptom score.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00217854
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Study Chair:||Mario Castro||Washington University School of Medicine|