Theophylline: A new way to overcome corticosteroid resistance?
Theophylline, when used at bronchodilator doses, is difficult to monitor due to its interaction with various drugs and its narrow therapeutic index. However, when theophylline is used at low doses it has anti-inflammatory properties and may enhance the activity of a key corticosteroid-associated corepressor protein, histone deacetylase (HDAC), which is reduced in COPD. Therefore, inhaled corticosteroids and low-dose theophylline may not only independently reduce airway inflammation in COPD, but they may act synergistically. In a study to test the hypothesis that the combination of inhaled corticosteroids and theophylline has a greater therapeutic effect than theophylline alone, 30 patients with COPD discontinued any treatments with inhaled corticosteroids (ICS) and underwent a run-in period of 2 weeks. They were then randomized to two treatment arms. Subjects in Arm 1 were given inhalation placebo and placebo theophylline capsules for the first four-week period, and those in Arm 2 were given inhaled fluticasone propionate (FP, 500 µg bid) and placebo theophylline capsules. After a two-week washout period, subjects in Arm 1 were given inhalation placebo plus active theophylline (250 mg bid) for a second four-week period, and subjects in Arm 2 received FP plus active theophylline. Subsequently, the trial was extended with an open-label repeat of Arm 2 and included seven subjects from the original trial. The researchers found that the combination treatment with fluticasone and theophylline significantly reduced total sputum eosinophils. In addition, they showed that the FEV1 % predicted significantly increased with the fluticasone-theophylline combination. The combination of FP plus theophylline increased forced mid-expiratory flow rate from 470 mL/s to 555 mL/s.
Editor’s comment: Combination therapy with an inhaled corticosteroid and low-dose theophylline may be helpful in treating airway inflammation in COPD patients.
Ford PA, Durham AK, Russell REK et al. Treatment effects of low-dose theophylline combined with an inhaled corticosteroid inCOPD. Chest 2010; 137(6): 1338-1344. source : Medical Journal Reviews WAO Provided by Widodo judarwanto, pediatrician
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