SELECTED ARTICLES FROM THE RECENT LITERATURE 2003

12/10/03

Airway tissue mast cell frequency may predict asthma worsening following inhaled steroid withdrawal

Summary
It has been recognized that not all asthma with similar degrees of clinical severity will respond equally to inhaled corticosteroid (ICS) therapy. Kraft et al of the National Jewish Medical and Research Center in Denver, CO have described a possible predictor of whether asthmatics controlled on adequate doses of ICS will relapse following ICS withdrawal. They reported a large, double-blind, randomized study comparing 3 sub-groups of an asthmatic population which had been well controlled on ICS (triamcinolone 800 mcg/day) for 6 weeks. A bronchial biopsy following broncho-alveolar lavage (BAL) was obtained in 45 of these patients s after the initial 6 weeks of therapy with ICS. In 2 sub-groups the ICS was stopped with substitution of either inhaled salmeterol (Sal) 42 mcg b.i.d. or placebo. The third sub-group was continued on the ICS dose employed during the previous 6 weeks. In 10 patients (3 of 9 Sal recipients, 7 of 10 placebo recipients) the asthma worsened prominently to the point where aggressive treatment was necessary. Such exacerbations were not seen in any patients continued on ICS therapy. When the bronchial findings obtained at the end of the initial 6 week ICS treatment period were analyzed, it was found that the frequency of mast cells in bronchial biopsies and BAL levels of tryptase, a mast cell marker, were significantly higher in those subjects who would subsequently exhibit worsening of their asthma during the succeeding 16 weeks.

Reference
Chest 2003; 124:42-50

Editor's Comments
These findings are quite interesting, yet puzzling. Although the sub-groups of asthmatics compared were not very large, the findings suggest that a high frequency of bronchial mast cells despite 6 weeks of ICS therapy predicts a greater likelihood of asthma worsening following ICS withdrawal. Other groups have reported a correlation between the clinical severity of asthma and the frequency of mast cells in and near the smooth muscle layer of the bronchi. But why was the asthma controlled by ICS therapy during the first 6 weeks in those with higher mast cell accumulation in the airways? Did the ICS inhibit mediator release from such mast cells? Certainly the tryptase release into the BAL fluid was not suppressed. Confirmation and extension of these provocative findings is needed.

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