A prospective randomized controlled study: Theophylline on oxidative stress and steroid sensitivity in chronic obstructive pulmonary disease patients

OBJECTIVE: Oxidative stress is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Corticosteroid fails to suppress inflammation and oxidative stress due to steroid resistance. Theophylline has an effect on histone deacetylase (HDAC) activity and improves steroid sensitivity in COPD. Given changes in oxidative stress associated with diminished corticosteroid effects, a clinical study in which antioxidants and free radicals are estimated can suggest a correlation between antioxidants, theophylline, and corticosteroid sensitivity. MATERIALS AND METHODS: A randomized controlled study was conducted in 60 participants divided into 4 groups: Group I (controls) - 15 normal healthy volunteers, Group II - COPD patients who received theophylline 300 mg + salbutamol 8 mg, Group III - patients who inhaled budesonide 400 μg + salbutamol 8 mg, and Group IV – theophylline 300 mg + inhaled budesonide 400 μg + salbutamol 8 mg 12 weeks. Blood samples were collected at the time of diagnosis and at 4-week interval for 3 months from all the groups and antioxidant parameters, spirometric % forced expiratory volume in 1 s (FEV(1)) were measured. RESULTS: The mean difference between groups was analyzed using one-way ANOVA. There was a significant increase in antioxidant enzymes such as catalase, glutathione (GSH) serum transferase, (P < 0.05), reduced GSH, and superoxide dismutase (P < 0.01) and a significant decrease in lipid peroxidation (P < 0.01) at 12 weeks of the study period. Postbronchodilator FEV(1) values have also shown a significant increase at 12 weeks (P < 0.01). CONCLUSION: Theophylline increases the expression and activity of HDAC and improves steroid sensitivity thereby decreases oxidative stress. Hence, novel therapeutic strategy is therefore the reversal of this corticosteroid resistance by increasing the expression and activity of HDAC achieved using corticosteroids along with theophylline.