Effect of slow-release theophylline on airway inflammation in bronchial asthma]

Theophylline has been used as a bronchodilator in acute and chronic asthma management but recent evidences suggest that it has anti-inflammatory effects. Therefore, we investigated the therapeutic effect of slow-release theophylline in mild to moderate asthmatic patients. Symptomatic 19 patients with mild asthma who were treated with inhaled beta 2-agonist alone, and 17 subjects with moderate asthma who were treated with moderate dose of inhaled corticosteroid (beclomethasone dipropionate, BDP, 400-800 micrograms/day) were enrolled to the present study. After two-week run-in period, slow-release theophylline was administered for six to eight weeks and asthma symptoms, respiratory function, airway inflammation evaluated by the inhalation of hypertonic saline, and airway reactivity to histamine were investigated during observation period and after treatment. Asthma symptom score was significantly improved after theophylline treatment in both groups. Morning peak expiratory flow was significantly elevated but FEV1 was not significantly improved by the additional treatment with slow-release theophylline in both groups. Significant decreases in the percentages of total and EG2 + eosinophils in induced sputum demonstrated that slow-release theophylline has anti-inflammatory effect in patients with asthma despite the treatment with inhaled corticosteroid. Because recent reports suggest that theophylline may act as an anti-inflammatory drug even in low dose concentration, we also investigated the effect of plasma theophylline concentration on the airway inflammation. Patients were divided into two groups by the plasma concentration of theophylline, more than 10 micrograms/mL which is necessary to dilate airway and below 10 micrograms/mL, referred to as low dose concentration of theophylline. The results suggest that the administration of slow-release theophylline significantly decreased the percentages of both total and EG2 + eosinophils in induced sputum in both concentration groups. However, airway reactivity to histamine did not significantly change by the treatment. Taken together, we conclude that low dose treatment of slow-release theophylline has an anti-inflammatory effect and treatment with slow-release theophylline alone or the additional use with inhaled corticosteroid is an effective therapy for the management of mild to moderate asthma.