EFFECT OF THEOPHYLLINE WITHDRAWAL ON AIRWAY INFLAMMATION IN ASTHMA

Theophylline has been used as a bronchodilator in acute and chronic as thma management, although there is accumulating evidence that it may h ave anti-inflammatory effects. We have investigated the effect of theo phylline withdrawal for 6 weeks in asthmatic subjects whose peak expir atory flow (PEF) readings were more than 80% of the predicted value an d its variability was less than 20% (Green Zone) by treatment with bot h a moderate dose of inhaled corticosteroids (BDP), 400-800 mu g/day) and low dose theophylline (400 mg/day) for more than 3 months. In 38 a sthmatic subjects, changes in clinical symptoms, respiratory function and airway inflammation detected with hypertonic saline induced sputum , and airway reactivity to histamine were investigated. One half of th e patients were randomly withdrawn from theophylline, while the other half continued to take the same dose of theophylline for a period of 6 weeks. Mean steady state plasma theophylline concentrations when rece iving treatment with theophylline were 8.08 mu g/mL in the theophyllin e withdrawal group and 7.64 mu g/mL in the control theophylline group, respectively. Although a significant increase in asthma symptoms emer ged in the theophylline group, there were no significant changes in th e theophylline administration group. In the theophylline withdrawal gr oup, there were small but significant falls in PEF in the morning, FEV 1 and V-50 at the end of the study period. Analysis of induced sputum showed that there was also a significant increase in the percentage of total and activated (EG2(+)) eosinophils only in those patients who w ithdrew from theophylline. These results indicate that chronic treatme nt with low dose theophylline exerts an anti-inflammatory effect and t hat the additional use of theophylline with inhaled corticosteroids pr ovides an effective treatment for moderate asthma. Taken together, we conclude that theophylline has long-term beneficial effects on the chr onic asthma management.