Inflammatory Processes in the Airway of Asthmatics With Persistent Bronchial Hyperreactivity

BACKGROUND:

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.

DESIGN NARRATIVE:

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.