The additive effect of theophylline on a combination of formoterol and tiotropium in stable COPD: A pilot study

Summary 

We explored the additive effect of titrated oral theophylline in patients with stable chronic obstructive pulmonary disease (COPD) who received both tiotropium, 18μg od, and formoterol, 12μg bid. Thirty-six patients with moderate-to-severe COPD were enrolled in this two-period trial. They were initially treated with formoterol+tiotropium for 4 weeks. After this first period, they were divided in two groups of 18 patients. Both groups continued with the initial treatment for further 4 weeks, but the first group received also placebo whereas the second group received oral theophylline. The combination therapy with formoterol+tiotropium induced a significant improvement in mean predose FEV₁ and FVC at the end of the first period, and a significant reduction in dyspnea score as measure by a visual analogic scale and in use of rescue salbutamol. The second period of treatment elicited a significant further improvement in lung function and reduction in dyspnea score and salbutamol use in both groups. On the contrary, differences in improvements in FEV₁ and FVC and reduction in dyspnea score and salbutamol use between theophylline and placebo arms at the end of the second treatment period were not significant, although 5 patients reported an important relief in dyspnea during the theophylline administration period. These findings question the importance of adding theophylline in stable COPD patients already treated with two long-acting bronchodilators, but also indicate the possibility that some of them can benefit from theophylline because of a symptomatic improvement.

Keywords: COPD, Tiotropium, Formoterol, Theophylline, Combination therapy