Formoterol versus short-acting beta-agonists as relief medication for adults and children with asthma.
BACKGROUND
Formoterol is a long-acting beta(2)-agonist but because it has a fast onset of action it can also be used as a relief medication.


OBJECTIVE
To asses the efficacy and safety of formoterol as reliever therapy in comparison to short-acting beta(2)-agonists in adults and children with asthma.


METHODS
We searched the Cochrane Airways Group Specialised Register and websites of clinical trial registers (for unpublished trial data), and we checked the Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was February 2010.


METHODS
Randomised, parallel-arm trials of at least 12 weeks duration in patients of any age and severity of asthma. Studies randomised patients to any dose of as-needed formoterol versus short-acting beta(2)-agonist. Concomitant use of inhaled corticosteroids or other maintenance medication was allowed, as long as this was not part of the randomised treatment regimen.


METHODS
Two authors independently selected trials for inclusion in the review. Outcome data were extracted by one author and checked by the second author. We sought unpublished data on primary outcomes.


RESULTS
This review includes eight studies conducted in 22,604 participants (mostly adults). Six studies compared formoterol as-needed to terbutaline whilst two studies compared formoterol with salbutamol as-needed. Background maintenance therapy varied across the trials. Asthma exacerbations and serious adverse events showed a direction of treatment effect favouring formoterol, of which one outcome reached statistical significance (exacerbations requiring a course of oral corticosteroids). In patients on short-acting beta(2)-agonists, 117 people out of 1000 had exacerbations requiring oral corticosteroids over 30 weeks, compared to 101 (95% CI 93 to 108) out of 1000 for patients on formoterol as-needed. In patients on maintenance inhaled corticosteroids there were also significantly fewer exacerbations requiring a course of oral corticosteroids on formoterol as-needed (Peto OR 0.75; 95% CI 0.62 to 0.91). There was one death per 1000 people on formoterol or on short-acting beta(2)-agonists.


CONCLUSIONS
In adults, formoterol was similar to short-acting beta(2)-agonists when used as a reliever, and showed a reduction in the number of exacerbations requiring a course of oral corticosteroids. Clinicians should weigh the relatively modest benefits of formoterol as-needed against the benefits of single inhaler therapy and the potential danger of long-term use of long-acting beta(2)-agonists in some patients. We did not find evidence to recommend changes to guidelines that suggest that long-acting beta(2)-agonists should be given only to patients already taking inhaled corticosteroids.There was insufficient information reported from children in the included trials to come to any conclusion on the safety or efficacy of formoterol as relief medication for children with asthma.
Welsh
Emma J
EJ
Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London, UK, SW17 0RE.
Cates
Christopher J
CJ
D000328:Adult; D000367:Age Factors; D000420:Albuterol / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use; D002648:Child; D004205:Cromolyn Sodium / Q000627:therapeutic use; D004983:Ethanolamines / Q000627:therapeutic use*; D000068759:Formoterol Fumarate; D006801:Humans; D017835:Nedocromil / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013726:Terbutaline / Q000627:therapeutic use
D001993:Bronchodilator Agents; D004983:Ethanolamines; D017835:Nedocromil; D019819:Budesonide; D013726:Terbutaline; D004205:Cromolyn Sodium; D000420:Albuterol; D000068759:Formoterol Fumarate
Respir Med. 2008 Mar;102(3):449-56
18023335
Pulm Pharmacol Ther. 2001;14(1):29-34
11162416
Clin Ther. 2008 Mar;30(3):560-71
18405796
Lancet. 2001 Jan 27;357(9252):257-61
11214127
Respir Med. 2003 Sep;97(9):1061-6
14509561
Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006363
18646149
Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001385
17253458
Eur Respir J. 2009 Oct;34(4):803-11
19797669
Respir Med. 2005 Apr;99(4):461-70
15763453
BMJ. 2003 Sep 6;327(7414):557-60
12958120
Respir Med. 2007 Mar;101(3):467-75
16949264
Evid Based Med. 2010 Apr;15(2):37-8
20436111
Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):622-5
1892303
J Allergy Clin Immunol. 2004 Jan;113(1):101-8
14713914
Eur Respir J. 2002 Oct;20(4):859-66
12412676
Eur Respir J. 2006 Mar;27(3):504-10
16507849
Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003135
16235315
Int J Clin Pract. 2005 Jan;59(1):62-8
15707467
Cochrane Database Syst Rev. 2008 Oct 08;(4):CD006923
18843738
BMJ. 2007 Sep 8;335(7618):513
17823193
J Allergy Clin Immunol. 2009 May;123(5):1083-9, 1089.e1-7
19368965
Eur Respir J. 2003 Nov;22(5):787-94
14621086
Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006924
19370661
Pediatr Pulmonol. 2003 Nov;36(5):391-8
14520721
Respir Med. 2001 Sep;95(9):753-8
11575897
Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007313
19370682
Br J Gen Pract. 2008 Jan;58(546):37-43
18186995
Lancet. 2006 Aug 26;368(9537):744-53
16935685
Cochrane Database Syst Rev. 2009 Jan 21;(1):CD007085
19160317