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

Division of Pulmonary and Critical Care Medicine; Department of Medicine; Division of Biostatistics; and Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri

Correspondence and requests for reprints should be addressed to Mario Castro, M.D., MPH, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St. Louis, MO 63110–1093. 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 days with inhaled fluticasone propionate (1,760 µg/day) followed by a withdrawal period that lasted until peak expiratory airflow decreased by 25% and FEV₁ by 15% or 6 weeks elapsed. After glucocorticoid withdrawal, 13 of 25 subjects reached the target, whereas 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 in only 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 (regulated upon activation, normal T cell expressed and secreted) in the airway epithelium without activation of the transcription factor nuclear factor-B. The pattern of glucocorticoid-sensitive inflammation during an asthma exacerbation is more reminiscent of an antiviral 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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