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Published ahead of print on January 15, 2004, doi:10.1164/rccm.200208-960OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 7, April 2004, 842-849

A more recent version of this article appeared on April 1, 2004
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Submitted on September 9, 2002
Accepted on January 13, 2004

Asthma Exacerbations After Glucocorticoid Withdrawal Reflects T Cell Recruitment to the Airway

Mario Castro1*, Sharon R Bloch1, Michelle V Jenkerson1, Steve DeMartino1, Daniel L Hamilos2, Rebecca B Cochran1, E Xueping1, Liang Zhang1, Haochuan Wang1, Joseph P Bradley1, Kenneth B Schechtman3, and Michael J Holtzman1

1 Division of Pulmonary and Critical Care Medicine and Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA, 2 Washington University School of Medicine, St. Louis, MO, USA, 3 Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA

* To whom correspondence should be addressed. E-mail: castrom{at}wustl.edu.

We reasoned that a prospective assessment of glucocorticoid withdrawal in subjects with asthma would provide insight into the basis for flares of the disease. We therefore enrolled 25 subjects with moderate persistent asthma and treated them for 30 d with inhaled fluticasone proprionate (1760 µg/d) followed by a withdrawal period that lasted until peak expiratory airflow decreased by 25% and forced expiratory volume in 1 sec by 15% or 6 wk elapsed. After glucocorticoid withdrawal, 13 of 25 subjects reached the target while 12 subjects did not. The number of eosinophils in bronchial biopsies was increased by glucocorticoid withdrawal in both groups, but increases in airway T cells were found only in those with exacerbation. T cell accumulation was a reflection of similar increases in both CD4+ and CD8+ T cells and was accompanied by increased expression of chemokine CCL5 (RANTES) in the airway epithelium without activation of the transcription factor NF-{kappa}B. The pattern of glucocorticoid-sensitive inflammation during an asthma exacerbation is more reminiscent of an anti-viral response than an eosinophil-predominant response to allergen and implies an independent role for airway T cells in mediating asthma flares and in determining glucocorticoid efficacy in the treatment of this disease.
Key words: airway inflammation, airway hyperreactivity, airway epithelium




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