Theophylline has been used as a bronchodilator in the treatment of COPD for over 70 years, but has lost popularity as better tolerated and more effective bronchodilators have been introduced. However, new insights into the molecular action of theophylline have raised the possibility that this old drug may come back into favour as an anti-inflammatory treatment and may even reverse steroid resistance in COPD.¹ A paper by Hirano et al in this issue of Thorax provides further support for the anti-inflammatory effects of theophylline in patients with COPD.²

CURRENT USE OF THEOPHYLLINE IN COPD

In the major guidelines for the treatment of COPD, theophylline is relegated to a third line bronchodilator after inhaled anticholinergics and β₂ agonists. Nevertheless, it is recognised that theophylline is a useful treatment in patients with severe COPD as its withdrawal leads to significant clinical worsening of the disease.³ Many older clinicians have been convinced by its clinical value in severe disease.

THEOPHYLLINE AS A BRONCHODILATOR

Traditionally, theophylline was used as a bronchodilator in the treatment of airway disease but, to achieve significant bronchodilatation comparable with that of a β₂ agonist, relatively high plasma concentrations are needed (10–20 mg/l). Theophylline relaxes human airway smooth muscle in vitro through inhibition of phosphodiesterases (PDE), enzymes that break down cyclic nucleotides in the …