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From the author

Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK

Received: July 27, 2004
Accepted August 6, 2004

We are grateful for A.R.L. Medford's interest in our study 1. The patients in our trial had relatively severe chronic obstructive pulmonary disease (COPD; mean forced expiratory volume in one second (FEV₁) 36% predicted), as did those in a companion study of the same treatment that used a different trial design 2. In both trials, budesonide via a dry powder reservoir delivery system was less effective in preventing exacerbations than fluticisone delivered in a slightly higher dose in the TRial of Inhaled STeroids ANd long-acting ß-agonists (TRISTAN) of patients with a mean FEV₁ 44% pred 3. These disparities may reflect differences in the dose given, the delivery system or the effectiveness of inhaled corticosteroids in more severe disease, and our data cannot resolve this point. However, a more recent analysis of the TRISTAN data set, which is currently being prepared for publication, suggests that the effect of the inhaled corticosteroid on exacerbation numbers was less marked in those patients with more severe disease, and this would be in keeping with the findings of our study. We were reassured to see that, in bothtrials, the budesonide-formoterol combination reduced exacerbation numbers significantly, despite the relatively limited impact of the inhaled corticosteroid given alone. The current guidance on the use of inhaled corticosteroids in COPD recommends that they should be added into maintenance bronchodilator therapy, which should ideally be provided by a long-acting inhaled bronchodilator 4, and theuse of inhaled corticosteroid as monotherapy to prevent exacerbations is not recommended.

Our statement about the benefits of combining treatment ina single inhaler was strictly factual, as we were not in a position to conduct the proposed comparison of fixed doses versus the same drug given in separate inhalers. Clearly, this isof practical relevance, but, unfortunately, calculating the statistical power of a study that could conclusively establish a difference between such treatment interventions suggests that it would have to be a substantially larger study than any that have been reported so far. We agree that there are good reasons for combining long-acting ß-agonists and an inhaled corticosteroid, but the data about dose flexibility in chronic obstructive pulmonary disease has not been explored. There may be some utility in delivering the drugs together in a fixed dose combination at the site of action, rather than potentially allowing for different patterns of airway deposition on individual inhaler actuations. Such concerns remain of theoretical interest, but are hard to test with our existing techniques and in representative populations of chronic obstructive pulmonary disease patients. There are certainly advantages of convenience and, potentially, of treatment adherence by giving both drugs together, but this will need to be established in future studies.

References

1. Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003;22:912–919.[Abstract/Free Full Text]
2. Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of budesonide/formoterol in the management of chronic obstructive pulmonary disease. Eur Respir J 2003;21:74–81.[Abstract/Free Full Text]
3. Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003;361:449–456.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
4. NHLBI/WHO Workshop Report, 2004. Global strategy forthe diagnosis, management and prevention of chronic obstructive pulmonary disease. www.goldcopd.com. Date last accessed: July 27 2004.

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