Molecular mechanism of the additive effects of leukotriene modifier in asthmatic patients receiving steroid therapy.

BACKGROUND

The addition of leukotriene modifier (LM) may be a useful approach for uncontrollable asthma despite treatment with inhaled corticosteroid (ICS), especially in asthmatics comorbid with allergic rhinitis (AR), although little is known about its molecular mechanism. We evaluated the additive effects of LM with ICS on pulmonary function and airway inflammation in asthmatics with or without AR.

METHODS

Eighteen uncontrolled steroid-treated asthmatics, nine with and nine without AR, were enrolled. Spirometry, peak expiratory flow (PEF) measurements, and exhaled breath condensate sampling were performed before and 8 weeks after LM administration. The lowest PEF over the course of one week, expressed as a percentage of the highest PEF (Min%Max PEF), was used as an index of fluctuation of the airway caliber. Airway cytokine expression was analyzed with a protein array.

RESULTS

A significant improvement in forced expiratory volume in one second as a percentage of the predicted value (%FEV(1)) and Min%Max PEF was seen in the subgroup of asthma with AR. Although there was no significant difference in the baseline cytokine values between the groups, the exhaled RANTES level was significantly reduced by LM in the asthma with AR group. The changes in the RANTES level were significantly related to the changes in the %FEV(1) and Min%Max PEF values.

CONCLUSIONS

LM caused a greater improvement in pulmonary function and airway inflammation in asthmatics with AR. The RANTES-mediated pathway may be involved in the improvement of the airflow limitation and airway lability by LM additive therapy in asthmatics receiving steroid therapy.