The influence of theophylline on maximal response to salbutamol in severe chronic obstructive pulmonary disease

Summary

We have previously shown that inhaled salbutamol further increases the bronchodilator response after the maximum effect of theophylline has been obtained in patients with severe chronic bronchitis. We now report the results of adding maximally effective doses of theophylline to the maximum response obtainable from salbutamol in ten of these patients. We constructed dose response curves to ensure maximum possible effect from salbutamol. Response plateaus (in nine out of ten patients) were achieved with cumulative doses of between 200 µg and 3,000 µg salbutamol and there was a significant response (p<0.05) in every subject: the mean FVC response was 1.1 l (ranging from 0.5 to 1.8 l) and the mean FEV₁ response was 0.4 l (ranging from 0.1 to 0.8 l). Theophylline, in their previously determined maximally effective doses, produced statistically significant (p<0.05) small further increases in both FVC (0.2 to 0.6 l) and FEV₁ (0.1 to 0.6 l) in four patients only. The other six did not respond. In patients classified as chronic bronchitics there is clearly a wide variation in response to bronchodilators and a surprising degree of reversibility can be achieved. But because of this variation in response, conventional drug doses may be too small in some cases. Ideally, each bronchodilator should be prescribed after some form of individual dose response studies. Although this acute study shows little or no benefit in the height of the bronchodilator response the usefulness of this combination can only really be decided after similar studies including the duration of effect in long term administration.