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

Abstract

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 micrograms and 3,000 micrograms salbutamol and there was a significant response (p less than 0.05) in every subject: the mean FVC response was 1.11 (ranging from 0.5 to 1.81) and the mean FEV1 response was 0.41 (ranging from 0.1 to 0.81). Theophylline, in their previously determined maximally effective doses, produced statistically significant (p less than 0.05) small further increases in both FVC (0.2 to 0.61) and FEV (0.1 to 0.61) 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.

Effects of formoterol, salmeterol or oxitropium bromide on airway responses to salbutamol in COPD

“…A positive correlation between maximum bronchodilator response and the dose of β 2 -adrenoceptor agonist used is not always observed. However, a 50% increase in FEV1 is obtained with 400 µg salbutamol and an increase in the dose of this agent may produce further increases in FEV1 [30]. In any case, the results of this study apparently refute the assertion that airway obstruction secondary to increased vagal tone, and is the only dominant reversible element in patients suffering from COPD.…”

Acute Respiratory Failure

“…Since methylxanthines have multiple side effects with considerable potential for serious toxicity, whereas inhaled bronchodilators are generally safe, a more relevant question is whether theophylline provides any additional benefit in patients already receiving inhaled bronchodilators at optimal dosage. Studies have shown that some patients (40-50%) [59,60] display additional bronchodilatation (increase in FEV 1 of 32% or 0.22 D [59] when theophylline is added to large doses of inhaled bronchodilator. Whether this additional bronchodilatation translates into improved exer-oxygen.…”

What role for theophylline?

“…If they are adequately informed and closely followed, a trial of theophylline in the mid to slightly lower therapeutic range (12)(13)(14)(15) jg/ml) is important for those in whom dyspnoea gradually assumes total dominion over their lives. (2) Severe asthmatic patients in whom oral corticosteroids are being used or may be otherwise necessary.…”