BMJ 2000;320:1368-1373 ( 20 May )

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Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA)

Stephen Shrewsbury, associate medical director, a Stephen Pyke, section head, respiratory statistics, a Mark Britton, consultant respiratory physician. b

a GlaxoWellcome UK, Stockley Park West, Uxbridge, Middlesex UB11 1BT, b St Peter's Hospital, Chertsey, Surrey KT16 0PZ

Correspondence to: S Shrewsbury sbs40926{at}glaxowellcome.com

Objective: To examine the benefits of adding salmeterol compared with increasing dose of inhaled corticosteroids.
Design: Systematic review of randomised, double blind clinical trials. Independent data extraction and validation with summary data from study reports and manuscripts. Fixed and random effects analyses.
Setting: EMBASE, Medline, and GlaxoWellcome internal clinical study registers.
Main outcome measures: Efficacy and exacerbations.
Results: Among 2055 trials of treatment with salmeterol, there were nine parallel group trials of >= 12 weeks with 3685 symptomatic patients aged >= 12 years taking inhaled steroid in primary or secondary care. Compared with response to increased steroids, in patients receiving salmeterol morning peak expiratory flow was greater at three months (difference 22.4 (95% confidence interval 15.0 to 30.0) litre/min, P<0.001) and six months (27.7 (19.0 to 36.4) litre/min, P<0.001). Forced expiratory volume in one second (FEV1) was also increased at three months (0.10 (0.04 to 0.16) litres, P<0.001) and six months (0.08 (0.02 to 0.14) litres, P<0.01), as were mean percentage of days and nights without symptoms (three months: days---12% (9% to 15%), nights---5% (3% to 7%); six months: days---15% (12% to 18%), nights---5% (3% to 7%); all P<0.001) and mean percentage of days and nights without need for rescue treatment (three months: days---17% (14% to 20%), nights---9% (7% to 11%); six months: days---20% (17 to 23%), nights---8% (6% to 11%); all P<0.001). Fewer patients experienced any exacerbation with salmeterol (difference 2.73% (0.43% to 5.04%), P=0.02), and the proportion of patients with moderate or severe exacerbations was also lower (2.42% (0.24% to 4.60%), P=0.03).
Conclusions: Addition of salmeterol in symptomatic patients aged 12 and over on low to moderate doses of inhaled steroid gives improved lung function and increased number of days and nights without symptoms or need for rescue treatment with no increase in exacerbations of any severity.


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  • Holgate, S. T., Holloway, J., Wilson, S., Bucchieri, F., Puddicombe, S., Davies, D. E. (2004). Epithelial-Mesenchymal Communication in the Pathogenesis of Chronic Asthma. Proc Am Thorac Soc 1: 93-98 [Abstract] [Full text]  
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  • Masoli, M, Weatherall, M, Holt, S, Beasley, R (2004). Clinical dose-response relationship of fluticasone propionate in adults with asthma. Thorax 59: 16-20 [Abstract] [Full text]  
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  • Bernstein, I. L. (2002). {beta}2-Agonists: Deja vu All Over Again : The Second-Generation Controversy. Chest 122: 763-765 [Full text]  
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  • Shrewsbury, S., Pyke, S., Sears, M. R. (2002). MIASMA : Asthma Exacerbation Reduction With Salmeterol. Chest 121: 1002-1003 [Full text]  
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  • Cates, C. (2001). Extracts from ""Clinical Evidence"": Chronic asthma. BMJ 323: 976-979 [Full text]  
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  • Holt, S., Suder, A., Weatherall, M., Cheng, S., Shirtcliffe, P., Beasley, R., Herxheimer, A. (2001). Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis Commentary: Dosage needs systematic and critical review. BMJ 323: 253-253 [Abstract] [Full text]  
  • Soler, M., Matz, J., Townley, R., Buhl, R., O'Brien, J., Fox, H., Thirlwell, J., Gupta, N., Della Cioppa, G. (2001). The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 18: 254-261 [Abstract] [Full text]  
  • Rabe, K.F., Schmidt, D.T. (2001). Pharmacological treatment of asthma today. Eur Respir J 18: 34S-40s [Abstract] [Full text]  
  • Holgate, S. T. (2001). Therapeutic Options for Persistent Asthma. JAMA 285: 2637-2639 [Full text]  
  • Sears, M. R. (2001). Deleterious Effects of Inhaled {beta}-Agonists : Short-Acting and Long-Acting Agents Differ. Chest 119: 1297-1299 [Full text]  
  • Bourdet, S. V., Williams, D. (2001). Management Considerations for Chronic Asthma. Journal of Pharmacy Practice 14: 108-125 [Abstract]  
  • Boulet, L.-P., Cockcroft, D. W., Speir, W. A. Jr (2001). Regularly Scheduled Inhaled Bronchodilators and Maintenance Asthma Therapy. Chest 119: 987-988 [Full text]  
  • Cicutto, L. (2001). Review: addition of salmeterol leads to improved lung function and fewer exacerbations in symptomatic asthma. Evid. Based Nurs. 4: 15-15 [Full text]  
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  • (2000). Adding Salmeterol to Inhaled Steroids Helps Symptomatic Asthma. JWatch General 2000: 1-1 [Full text]  

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