Review: addition of salmeterol leads to improved lung function and fewer exacerbations in symptomatic For correspondence:Dr S Shrewsbury,Respiratory ClinicalShrewsbury S, Pyke S, Britton M. Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). BMJ 2000 May 20;320:1368–73. GlaxoWellcome Research& Development, FiveMoore Drive, PO BoxQUESTION: In patients with symptomatic asthma who are currently taking inhaled
steroids, does adding salmeterol improve lung function and reduce symptoms and
exacerbations compared with increasing the dose of inhaled corticosteroids?
+1 919 483 8835. [email protected]Data sources Mean percentage (95% CI) of days and nights without symptoms or use of rescue
Studies were identified by searching EMBASE/Excerpta
treatment (in favour of added salmeterol) (all p<0.001)
Medica, Medline, and GlaxoWellcome databases (1985
Outcomes Study selection
Studies were selected if they were randomised, double
blind, controlled trials comparing the addition ofsalmeterol to the current dose of inhaled steroid with anincreased dose (at least doubling) of the current inhaledsteroid for >12 weeks in adolescents and adults with
>1 exacerbations of asthma according to severity between treatment withsalmeterol and increased dose of inhaled steroid†ARR favouring salmeterol Outcomes NNT (CI)† Data extraction Data were extracted on patient characteristics; treatment
type, dose, and duration; and outcome measures based
on the intention to treat population. Individual patient
†Abbreviations defined in glossary; †CI calculated from data in article.
datasets were obtained and exacerbation severity wasassessed by 2 independent reviewers. Main results COMMENTARY
9 trials involving 3685 patients met the selection criteria.
Despite the use of inhaled corticosteroids, many asthma patients continue to experience
Mean morning peak expiratory flow (PEF) and forced
symptoms. The meta-analysis by Shrewsbury et al concludes that in patients experiencing
expiratory volume in one second (FEV1) were greater in
symptoms despite using low to moderate doses of inhaled corticosteroids, the addition of
those who received added salmeterol compared with
salmeterol (a long acting -agonist) is more effective than increasing the dosage of inhaled
those treated with an increased dose of inhaled steroids
steroids. Readers should be alert to the fact that all 9 included studies were sponsored by
(table 1). Mean percentage of days and nights without
GlaxoWellcome, that 2 of the 3 authors are company employees, and that GlaxoWellcome
symptoms or use of rescue treatment was higher among
manufactures Serevent (salmeterol xinafoate).
patients receiving salmeterol (table 2). Total exacerba-
Patients showed an increase in lung function as evidenced by improvements in PEF and
FEV at 3 and 6 months. The authors explain, however, that these findings are not surpris-
tions and moderate or severe exacerbations were
ing given that in most of the studies, a requirement for study entry was a demonstrable,
reduced with the addition of salmeterol compared with
clinically relevant response to -agonists. For all exacerbations, the number needed to treat
an increased dose of inhaled steroids (table 3).
was 37, which means that the addition of salmeterol to treatment with inhaled steroids in37 patients with symptoms would prevent one exacerbation in one additional patient,
Conclusion
compared with at least doubling the dosage of inhaled steroids.
In patients with symptomatic asthma who are currently
The review supports a decision to add inhaled salmeterol instead of doubling or
taking low to moderate dose inhaled steroids (eg,
tripling the current dose of inhaled corticosteroids for individuals with asthma who con-tinue to experience symptoms despite regular use of inhaled corticosteroids. This is an
beclomethasone dipropionate, 400 g/d or equivalent),
important option given the potential side effects of high dose inhaled steroids, patients’
the addition of salmeterol leads to improved lung func-
fears about the use of inhaled steroids, and the desire to identify the lowest dose of inhaled
tion, an increased number of days and nights without
steroids needed. This observation is consistent with the recommendations of current
symptoms or need for rescue medication, and fewer
asthma guidelines.1 2 It is important to remember that salmeterol is not intended as
monotherapy for asthma because of its lack of anti-inflammatory properties. Assistant Professor, University of TorontoTable 1 Mean differences in peak expiratory flow (PEF) and forcedAcute Care Nurse Practitioner-Respirologyexpiratory volume in one second (FEV ) between treatment withsalmeterol v an increased dose of inhaled steroids in symptomaticUniversity Health Network, Toronto, Ontario, Canadaasthma (in favour of added salmeterol) (all p<0.001 except * p<0.01)
1 Boulet LP, Becker A, Berube D, et al. Canadian asthma consensus report, 1999. Canadian
Outcomes
Asthma Consensus Group. CMAJ 1999;161:S1–61.
2 National Asthma Education and Prevention Program. Guidelines for the diagnosis and man-agement of asthma: expert panel report 2. Bethesda, MD: US Department of Health andHuman Services; 1997. Review: addition of salmeterol leads to improved lung function and fewer exacerbations in symptomatic asthma Evid Based Nurs 2001 4: 15doi: 10.1136/ebn.4.1.15
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