Thorax 1999;54:207-212 ( March )

Addition of salmeterol versus doubling the dose of fluticasone propionate in patients with mild to moderate asthma

J A van Noord,^a A J M Schreurs,^b S J M Mol,^c P G H Mulder^d

^a Department of Respiratory Diseases, Atrium Medisch Centrum, 6419 PC Heerlen, The Netherlands, ^b Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands, ^c Sint Joseph Hospital, Veldhoven, The Netherlands, ^d Department of Epidemiology and Biostatistics, Erasmus University, Rotterdam, The Netherlands

Correspondence to: Dr J A van Noord.

Received 4 June 1998; Returned to authors 21 July 1998; Revised version received 12 October 1998; Accepted for publication 17 November 1998

BACKGROUNDThe objective of this multicentre, randomised, double blind, parallel group study was to compare the efficacy and safety of the addition of salmeterol with that of doubling the dose of fluticasone propionate in asthmatic patients not controlled by a low or intermediate dose of inhaled corticosteroids.
METHODSAfter a four week run in period of treatment with fluticasone propionate (100 µg twice daily if pre-trial dose was 400-600 µg inhaled corticosteroids or 250 µg twice daily if pre-trial dose was 800-1200 µg inhaled corticosteroids), 274 patients were randomised to treatment for 12 weeks with either salmeterol 50 µg twice daily plus the run in dose of fluticasone propionate or twice the run in dose of fluticasone propionate (200 or 500 µg twice daily). Outcome measures were daily records of peak expiratory flow (PEF), symptom scores, and clinic lung function.
RESULTSThe improvements in both the morning and evening PEF were better in the salmeterol than in the fluticasone propionate group, the mean increase in morning PEF being 19 l/min higher (95% CI 11.0 to 26.1) and in evening PEF being 16 l/min (95% CI 18.4 to 24.0) higher in the salmeterol group. The increase in forced expiratory volume in one second (FEV₁) was 0.09 l greater in the salmeterol group than in the fluticasone propionate group after four weeks of treatment (95% CI 0.01 to 0.18), but not after 12 weeks. Both regimens showed an increase in symptom free days and a reduction in the need for rescue salbutamol both during the day and the night, but these improvements were greater in the salmeterol group. There were no significant differences between the groups in adverse effects or in the number of rescue courses of oral corticosteroids.
CONCLUSIONSIn this group of patients still symptomatic despite 100 or 250 µg fluticasone propionate twice daily, the addition of salmeterol caused a greater improvement in lung function and symptom control than doubling the dose of fluticasone propionate.

Keywords: salmeterol; fluticasone propionate; asthma

---

© 1999 by Thorax
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Bateman, E., Nelson, H., Bousquet, J., Kral, K., Sutton, L., Ortega, H., Yancey, S. (2008). Meta-analysis: Effects of Adding Salmeterol to Inhaled Corticosteroids on Serious Asthma-Related Events. ANN INTERN MED 149: 33-42 [Abstract] [Full Text]  
• Masoli, M, Weatherall, M, Holt, S, Beasley, R (2005). Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma. Thorax 60: 730-734 [Abstract] [Full Text]  
• Sin, D. D., Man, J., Sharpe, H., Gan, W. Q., Man, S. F. P. (2004). Pharmacological Management to Reduce Exacerbations in Adults With Asthma: A Systematic Review and Meta-analysis. JAMA 292: 367-376 [Abstract] [Full Text]  
• Lalloo, U. G., Malolepszy, J., Kozma, D., Krofta, K., Ankerst, J., Johansen, B., Thomson, N. C. (2003). Budesonide and Formoterol in a Single Inhaler Improves Asthma Control Compared With Increasing the Dose of Corticosteroid in Adults With Mild-to-Moderate Asthma. Chest 123: 1480-1487 [Abstract] [Full Text]  
• Price, D B, Hernandez, D, Magyar, P, Fiterman, J, Beeh, K M, James, I G, Konstantopoulos, S, Rojas, R, van Noord, J A, Pons, M, Gilles, L, Leff, J A (2003). Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax 58: 211-216 [Abstract] [Full Text]  
• Rabe, K.F., Schmidt, D.T. (2001). Pharmacological treatment of asthma today. Eur Respir J 18: 34S-40s [Abstract] [Full Text]  
• Knox, A.J., Zhu, Y.M., Pang, L. (2001). Do long-acting {beta}2-adrenoceptor agonists enhance the anti-inflammatory effect of glucocorticoids in asthma?. Eur Respir J 17: 1059-1061 [Full Text]  
• Lemanske, R. F. Jr, Sorkness, C. A., Mauger, E. A., Lazarus, S. C., Boushey, H. A., Fahy, J. V., Drazen, J. M., Chinchilli, V. M., Craig, T., Fish, J. E., Ford, J. G., Israel, E., Kraft, M., Martin, R. J., Nachman, S. A., Peters, S. P., Spahn, J. D., Szefler, S. J., for the Asthma Clinical Research Network of the Na, (2001). Inhaled Corticosteroid Reduction and Elimination in Patients With Persistent Asthma Receiving Salmeterol: A Randomized Controlled Trial. JAMA 285: 2594-2603 [Abstract] [Full Text]  
• Bourdet, S. V., Williams, D. (2001). Management Considerations for Chronic Asthma. Journal of Pharmacy Practice 14: 108-125 [Abstract]  
• Jones, S.L., Cowan, J.O., Flannery, E.M., Hancox, R.J., Herbison, G.P., Taylor, D.R. (2001). Reversing acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol. Eur Respir J 17: 368-373 [Abstract] [Full Text]  
• Lipworth, B. J., Dempsey, O. J., Aziz, I. (2000). Functional Antagonism With Formoterol and Salmeterol in Asthmatic Patients Expressing the Homozygous Glycine-16 {beta}2-Adrenoceptor Polymorphism. Chest 118: 321-328 [Abstract] [Full Text]  
• Taylor, D R, Hancox, R J (2000). Interactions between corticosteroids and beta agonists. Thorax 55: 595-602 [Full Text]  
• Shrewsbury, S., Pyke, S., Britton, M. (2000). Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 320: 1368-1373 [Abstract] [Full Text]  
• Lipworth, B. J., Baraniuk, J. N. (2000). Use of Fluticasone in Asthma. Chest 117: 611-613 [Full Text]  
• (2000). The use of inhaled corticosteroids in adults with asthma. DTB 38: 5-8 [Abstract] [Full Text]  
• TATTERSFIELD, A E, HARRISON, T W (1999). Step 3 of the asthma guidelines. Thorax 54: 753-754 [Full Text]