Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2012 Mar 14;2012(3):CD007695.
doi: 10.1002/14651858.CD007695.pub3.

Regular treatment with formoterol versus regular treatment with salmeterol for chronic asthma: serious adverse events

Christopher J Cates  1 , Toby J Lasserson
Affiliations
Meta-Analysis

Regular treatment with formoterol versus regular treatment with salmeterol for chronic asthma: serious adverse events

Christopher J Cates et al. Cochrane Database Syst Rev. .

Abstract

Background: An increase in serious adverse events with both regular formoterol and regular salmeterol in chronic asthma has been demonstrated in previous Cochrane reviews.

Objectives: We set out to compare the risks of mortality and non-fatal serious adverse events in trials which have randomised patients with chronic asthma to regular formoterol versus regular salmeterol.

Search methods: We identified trials using the Cochrane Airways Group Specialised Register of trials. We checked manufacturers' websites of clinical trial registers for unpublished trial data and also checked Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was January 2012.

Selection criteria: We included controlled, parallel-design clinical trials on patients of any age and with any severity of asthma if they randomised patients to treatment with regular formoterol versus regular salmeterol (without randomised inhaled corticosteroids), and were of at least 12 weeks' duration.

Data collection and analysis: Two authors independently selected trials for inclusion in the review and extracted outcome data. We sought unpublished data on mortality and serious adverse events from the sponsors and authors.

Main results: The review included four studies (involving 1116 adults and 156 children). All studies were open label and recruited patients who were already taking inhaled corticosteroids for their asthma, and all studies contributed data on serious adverse events. All studies compared formoterol 12 μg versus salmeterol 50 μg twice daily. The adult studies were all comparing Foradil Aerolizer with Serevent Diskus, and the children's study compared Oxis Turbohaler to Serevent Accuhaler. There was only one death in an adult (which was unrelated to asthma) and none in children, and there were no significant differences in non-fatal serious adverse events comparing formoterol to salmeterol in adults (Peto odds ratio (OR) 0.77; 95% confidence interval (CI) 0.46 to 1.28), or children (Peto OR 0.95; 95% CI 0.06 to 15.33). Over a six-month period, in studies involving adults that contributed to this analysis, the percentages with serious adverse events were 5.1% for formoterol and 6.4% for salmeterol; and over a three-month period the percentages of children with serious adverse events were 1.3% for formoterol and 1.3% for salmeterol.

Authors' conclusions: We identified four studies comparing regular formoterol to regular salmeterol (without randomised inhaled corticosteroids, but all participants were on regular background inhaled corticosteroids). The events were infrequent and consequently too few patients have been studied to allow any firm conclusions to be drawn about the relative safety of formoterol and salmeterol. Asthma-related serious adverse events were rare and there were no reported asthma-related deaths.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
3
3
Forest plot of comparison: 1 Regular formoterol versus regular salmeterol, outcome: 1.1 All‐cause mortality.
4
4
Forest plot of comparison: 1 Regular formoterol versus regular salmeterol, outcome: 1.2 All‐cause SAEs.
5
5
Forest plot of comparison: 1 Regular formoterol versus regular salmeterol, outcome: 1.3 Asthma‐related SAEs.
6
6
Changes in asthma mortality (5 to 34 age group) in three countries in relation to the introduction of isoprenaline forte in the UK and New Zealand and of fenoterol in New Zealand. (From Blauw 1995. With permission from the Lancet).
1.1
1.1. Analysis
Comparison 1 Regular formoterol versus regular salmeterol, Outcome 1 All‐cause mortality.
1.2
1.2. Analysis
Comparison 1 Regular formoterol versus regular salmeterol, Outcome 2 All‐cause SAEs.
1.3
1.3. Analysis
Comparison 1 Regular formoterol versus regular salmeterol, Outcome 3 Asthma‐related SAEs.
1.4
1.4. Analysis
Comparison 1 Regular formoterol versus regular salmeterol, Outcome 4 All‐cause SAEs (Sensitivity analysis).
1.5
1.5. Analysis
Comparison 1 Regular formoterol versus regular salmeterol, Outcome 5 Asthma‐related SAEs (Sensitivity analysis).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Condemi 2001 {published data only}
    1. Condemi JJ. Comparison of the efficacy of formoterol and salmeterol in patients with reversible obstructive airway disease: a multicenter, randomized, open‐label trial. Clinical Therapeutics 2001; Vol. 23, issue 9:1529‐41. - PubMed
Everden 2004 {published data only}
    1. Everden P, Campbell M, Harnden C, McGoldrick H, Bodalia B, Manion V, et al. Eformoterol Turbohaler compared with salmeterol by dry powder inhaler in asthmatic children not controlled on inhaled corticosteroids. Pediatric Allergy and Immunology 2004; Vol. 15, issue 1:40‐7. - PubMed
    1. Everden P, Lloyd A, Hutchinson J, Plumb J. Cost‐effectiveness of eformoterol Turbohaler versus salmeterol Accuhaler in children with symptomatic asthma. Respiratory Medicine 2002; Vol. 96, issue 4:250‐8. - PubMed
    1. Everden P, Reynia S, Lloyd AC, Hutchinson JL, Plumb JM. Economic evaluation of eformoterol compared with salmeterol in children aged 6‐17 with symptomatic asthma in the UK: cost‐effectiveness results of the FACT study. European Respiratory Journal 2001; Vol. 18, issue Suppl 33:122s.
Gabbay 1998 {published data only}
    1. Gabbay MB, Kane H, Benedetto G. A comparison of formoterol and salmeterol dry powders in the treatment of nocturnal asthma [abstract]. European Respiratory Journal. Supplement. 1998; Vol. 12, issue Suppl 28:325S.
Vervloet 1998 {published data only}
    1. Rutten van Molken MP, Doorslaer EK, Till MD. Cost‐effectiveness analysis of formoterol versus salmeterol in patients with asthma. Pharmacoeconomics 1998; Vol. 14, issue 6:671‐84. - PubMed
    1. Sanguinetti CM, Duce F, Quebe Fehling E, Della Cioppa G, Benedetto G. A 6‐month open comparison between formoterol and salmeterol dry powders in patients with reversible obstructive airway disease. European Respiratory Journal 1997; Vol. 10, issue Suppl 25:241S.
    1. Vervloet D, Ekstrom T, Pela R, Duce Gracia F, Kopp C, Silvert BD, et al. A 6‐month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease. Respiratory Medicine 1998; Vol. 92, issue 6:836‐42. - PubMed

References to studies excluded from this review

Brambilla 2003 {published data only}
    1. Brambilla C, Gros V, Bourdeix I. Formoterol 12 mug BID administered via single‐dose dry powder inhaler in adults with asthma suboptimally controlled with salmeterol or on‐demand salbutamol: a multicenter, randomized, open‐label, parallel‐group study. Clinical Therapeutics 2003; Vol. 25, issue 7:2022‐36. - PubMed
Campbell 1999 {published data only}
    1. Campbell LM, Anderson TJ, Parashchak MR, Burke CM, Watson SA, Turbitt ML. A comparison of the efficacy of long‐acting beta 2‐agonists: eformoterol via Turbohaler and salmeterol via pressurized metered dose inhaler or Accuhaler, in mild to moderate asthmatics. [Force Research Group corrected and republished with original paging, article originally printed in Respiratory Medicine 1999 Apr;934:236‐44]. Respiratory Medicine 1999; Vol. 93, issue 7:236‐44. - PubMed
Eryonucu 2005 {published data only}
    1. Eryonucu B, Uzun K, Guler N, Tuncer M, Sezgi C. Comparison of the short‐term effects of salmeterol and formoterol on heart rate variability in adult asthmatic patients. Chest 2005; Vol. 128, issue 3:1136‐9. - PubMed
Heijerman 1999 {published data only}
    1. Heijerman HG, Dekker FW, Rammeloo RH, Roldaan AC, Sinninghe HE. Similar efficacy of formoterol via turbuhaler and salmeterol via diskhaler in the treatment of asthma. European Respiratory Society; 1999 Oct 9‐13; Madrid, Spain 1999:[P2209].
Larsson 1990 {published data only}
    1. Larsson S. Long‐term studies on long‐acting sympathomimetics. Lung 1990; Vol. 168, issue Suppl:22‐4. - PubMed
Lemaigre 2006 {published data only}
    1. Lemaigre V, Bergh O, Smets A, Peuter S, Verleden GM. Effects of long‐acting bronchodilators and placebo on histamine‐induced asthma symptoms and mild bronchus obstruction. Respiratory Medicine 2006; Vol. 100, issue 2:348‐53. - PubMed
Novartis 2005 {published data only}
    1. Novartis. A 12‐month multicenter, randomized, double‐blind, double‐dummy trial to examine the long‐term tolerability of formoterol 10µg via the multiple dose dry powder inhaler (MDDPI), both as twice daily maintenance therapy and as on‐demand use in addition to maintenance in patients with persistent asthma. http://pharma.us.novartis.com/ 2005.
Pohunek 2004 {published data only}
    1. Pohunek P, Matulka M, Rybnicek O, Kopriva F, Honomichlova H, Svobodova T. Dose‐related efficacy and safety of formoterol (Oxis) Turbuhaler compared with salmeterol Diskhaler in children with asthma. Pediatric Allergy and Immunology 2004; Vol. 15:32‐9. - PubMed
Sill 1999 {published data only}
    1. Sill V, Bartuschka B, Villiger B, Ortland C, Domej W. Changes in specific airway resistance after powder inhalation of formoterol or salmeterol in moderate bronchial asthma. Pneumologie 1999; Vol. 53, issue 1:4‐9. - PubMed
van der Woude 2004 {published data only}
    1. Woude HJ, Postma DS, Politiek MJ, Winter TH, Aalbers R. Relief of dyspnoea by beta2‐agonists after methacholine‐induced bronchoconstriction. Respiratory Medicine 2004; Vol. 98, issue 9:816‐20. - PubMed
van Veen 2003 {published data only}
    1. Veen A, Weller FR, Wierenga EA, Jansen HM, Jonkers RE. A comparison of salmeterol and formoterol in attenuating airway responses to short‐acting beta2‐agonists. Pulmonary Pharmacology and Therapeutics 2003; Vol. 16, issue 3:153‐61. - PubMed
Verini 1998 {published data only}
    1. Verini M, Verrotti A, Greco R, Chiarelli F. Comparison of the bronchodilator effect of inhaled short‐ and long‐acting beta2‐agonists in children with bronchial asthma. A randomised trial. Clinical Drug Investigation 1998; Vol. 16, issue 1:19‐24. - PubMed
Von Berg 2003 {published data only}
    1. Berg A, Papageorgiou Saxoni F, Wille S, Carrillo T, Kattamis C, Helms PJ. Efficacy and tolerability of formoterol Turbuhaler in children. International Journal of Clinical Practice 2003; Vol. 57:852‐6. - PubMed

Additional references

Altman 2003
    1. Altman DG, Bland JM. Statistics notes: interaction revisited: the difference between two estimates. BMJ 2003;326(7382):219. - PMC - PubMed
Anderson 2006
    1. Anderson GP. Current issues with beta(2)‐adrenoceptor agonists ‐ pharmacology and molecular and cellular mechanisms. Clinical Reviews in Allergy and Immunology 2006; Vol. 31, issue 2‐3:119‐30. - PubMed
Arnold 1985
    1. Arnold JMO, O'Connor PC, Riddell JG, Harron DWG, Shanks RG, McDevitt DG. Effects of the beta‐2‐adrenoceptor antagonist ici‐118,551 on exercise tachycardia and isoprenaline‐induced beta‐adrenoceptor responses in man. British Journal of Clinical Pharmacology 1985; Vol. 19, issue 5:619‐30. - PMC - PubMed
Barnes 1993
    1. Barnes PJ. Beta‐adrenoceptors on smooth‐muscle, nerves and inflammatory cells. Life Sciences 1993; Vol. 52, issue 26:2101‐9. - PubMed
Barnes 1995
    1. Barnes PJ. Beta‐adrenergic receptors and their regulation. American Journal of Respiratory and Critical Care Medicine 1995; Vol. 152, issue 3:838‐60. - PubMed
Bennett 1994
    1. Bennett JA, Smyth ET, Pavord ID, Wilding PJ, Tattersfield AE. Systemic effects of salbutamol and salmeterol in patients with asthma. Thorax 1994; Vol. 49, issue 8:771‐4. - PMC - PubMed
Bijl‐Hofland 2001
    1. Bijl‐Hofland ID, Cloosterman SG, Folgering HT, Elshout FJ, Weel C, Schayck CP. Inhaled corticosteroids, combined with long‐acting beta(2)‐agonists, improve the perception of bronchoconstriction in asthma. American Journal of Respiratory and Critical Care Medicine 2001; Vol. 164, issue 5:764‐9. - PubMed
Blauw 1995
    1. Blauw GJ, Westendorp RGJ. Asthma deaths in New Zealand ‐ whodunnit. The Lancet 1995;345:2‐3. - PubMed
Brown 1983
    1. Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta‐2‐receptor stimulation by circulating epinephrine. New England Journal of Medicine 1983; Vol. 309, issue 23:1414‐9. - PubMed
Burgess 1991
    1. Burgess CD, Windom HH, Pearce N, Marshall S, Beasley R, Siebers RWL, et al. Lack of evidence for beta‐2 receptor selectivity ‐ a study of metaproterenol, fenoterol, isoproterenol, and epinephrine in patients with asthma. American Review of Respiratory Disease 1991; Vol. 143, issue 2:444‐6. - PubMed
Burggraaf 2001
    1. Burggraaf J, Westendorp RGJ, in't Veen J, Schoemaker RC, Sterk PJ, Cohen AF, et al. Cardiovascular side effects of inhaled salbutamol in hypoxic asthmatic patients. Thorax 2001; Vol. 56, issue 7:567‐9. - PMC - PubMed
Cates 2008
    1. Cates CJ, Cates MJ. Regular treatment with salmeterol for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2008, Issue 3. [DOI: 10.1002/14651858.CD006363.pub2] - DOI - PMC - PubMed
Cates 2008a
    1. Cates CJ, Cates MJ, Lasserson TJ. Regular treatment with formoterol for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD006923.pub2] - DOI - PubMed
Cates 2009
    1. Cates CJ, Lasserson TJ, Jaeschke R. Regular treatment with formoterol and inhaled steroids for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD006924.pub2] - DOI - PubMed
Cates 2009a
    1. Cates CJ, Lasserson TJ, Jaeschke R. Regular treatment with salmeterol and inhaled steroids for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD006922.pub2] - DOI - PubMed
Cates 2011
    1. Cates CJ, Lasserson TJ. Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events. Cochrane Database of Systematic Reviews 2011, Issue 12. [DOI: 10.1002/14651858.CD007694.pub2] - DOI - PMC - PubMed
Cockcroft 1993
    1. Cockcroft DW, McParland CP, Britto SA, Swystun VA, Rutherford BC. Regular inhaled salbutamol and airway responsiveness to allergen. Lancet 1993; Vol. 342, issue 8875:833‐7. - PubMed
Collins 1969
    1. Collins JM, McDevitt DG, Shanks RG, Swanton JG. Cardio‐toxicity of isoprenaline during hypoxia. British Journal of Pharmacology 1969; Vol. 36, issue 1:35‐7. - PMC - PubMed
Crane 1989
    1. Crane J, Pearce N, Flatt A, Burgess C, Jackson R, Kwong T, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981‐83 ‐ case‐control study. Lancet 1989; Vol. 1, issue 8644:917‐22. - PubMed
Ducharme 2006
    1. Ducharme FM, Lasserson TJ, Cates CJ. Addition to inhaled corticosteroids of long‐acting beta2‐agonists versus anti‐leukotrienes for chronic asthma. Cochrane Database of Systematic Reviews 2011, Issue 8. [DOI: 10.1002/14651858.CD003137.pub3] - DOI - PubMed
Giembycz 2006
    1. Giembycz MA, Newton R. Beyond the dogma: novel ß2‐adrenoceptor signalling in the airways. European Respiratory Journal 2006;27(6):1286‐306. - PubMed
Grainger 1991
    1. Grainger J, Woodman K, Pearce N, Crane J, Burgess C, Keane A, et al. Prescribed fenoterol and death from asthma in New Zealand, 1981‐7 ‐ a further case‐control study. Thorax 1991; Vol. 46, issue 2:105‐11. - PMC - PubMed
Greenstone 2005
    1. Greenstone IR, Ni Chroinin M, Masse V, Danish A, Magdalinos H, Zhang X, et al. Combination of inhaled long‐acting beta2‐agonists and inhaled steroids versus higher dose of inhaled steroids in children and adults with persistent asthma. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD005533] - DOI - PubMed
Guhan 2000
    1. Guhan AR, Cooper S, Oborne J, Lewis S, Bennett J, Tattersfield AE. Systemic effects of formoterol and salmeterol: a dose‐response comparison in healthy subjects. Thorax 2000; Vol. 55, issue 8:650‐6. - PMC - PubMed
Hall 1989
    1. Hall JA, Petch MC, Brown MJ. Intracoronary injections of salbutamol demonstrate the presence of functional beta‐2‐adrenoceptors in the human‐heart. Circulation Research 1989; Vol. 65, issue 3:546‐53. - PubMed
Hanania 2002
    1. Hanania NA, Sharfkhaneh A, Barber R, Dickey BF. Beta‐agonist intrinsic efficacy ‐ measurement and clinical significance. American Journal of Respiratory and Critical Care Medicine 2002; Vol. 165, issue 10:1353‐8. - PubMed
Hanania 2007
    1. Hanania NA, Moore RH, Zimmerman JL, Miller CT, Bag R, Sharafkhaneh A, et al. The role of intrinsic efficacy in determining response to beta(2)‐agonist in acute severe asthma. Respiratory Medicine 2007; Vol. 101, issue 5:1007‐14. - PubMed
Hancox 1999
    1. Hancox RJ, Aldridge RE, Cowan JO, Flannery EM, Herbison GP, McLachlan CR, et al. Tolerance to beta‐agonists during acute bronchoconstriction. European Respiratory Journal 1999; Vol. 14, issue 2:283‐7. - PubMed
Hancox 2006a
    1. Hancox RJ. Concluding remarks: can we explain the association of beta‐agonists with asthma mortality? A hypothesis. Clinical Reviews in Allergy and Immunology 2006; Vol. 31, issue 2‐3:279‐88. [1080‐0549: (Print)] - PubMed
Haney 2006
    1. Haney S, Hancox RJ. Recovery from bronchoconstriction and bronchodilator tolerance. Clinical Reviews in Allergy and Immunology 2006; Vol. 31, issue 2‐3:181‐96. - PubMed
Harvey 1982
    1. Harvey JE, Tattersfield AE. Airway response to salbutamol ‐ effect of regular salbutamol inhalations in normal, atopic, and asthmatic subjects. Thorax 1982; Vol. 37, issue 4:280‐7. - PMC - PubMed
Jaeschke 2008
    1. Jaeschke R, O'Byrne PM, Nair P, Mejza F, Lesniak W, Brozek J, et al. The safety of formoterol among patients with asthma using inhaled corticosteroids. Systematic review and meta‐analysis. Polskie Archiwum Medycyny Wewnetrznej 2008; Vol. 118, issue 11:627‐35. - PubMed
Jaeschke 2008a
    1. Jaeschke R, O'Byrne PM, Mejza F, Nair P, Lesniak W, Brozek J, et al. The safety of long‐acting beta‐agonists among patients with asthma using inhaled corticosteroids: systematic review and meta‐analysis. American Journal of Respiratory and Critical Care Medicine 2008; Vol. 178, issue 10:1009‐16. - PubMed
Jones 2001
    1. Jones SL, Cowan JO, Flannery EM, Hancox RJ, Herbison GP, Taylor DR. Reversing acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol. European Respiratory Journal 2001; Vol. 17, issue 3:368‐73. - PubMed
Lee 2003
    1. Lee DKC, Jackson CM, Currie GP, Cockburn WJ, Lipworth BJ. Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma. British Journal of Clinical Pharmacology 2003; Vol. 56, issue 5:494‐500. - PMC - PubMed
Lipworth 1989
    1. Lipworth BJ, Struthers AD, McDevitt DG. Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high‐dose inhaled salbutamol in asthmatics. American Review of Respiratory Disease 1989; Vol. 140, issue 3:586‐92. - PubMed
Lipworth 1992
    1. Lipworth BJ, McDevitt DG. Inhaled beta‐2‐adrenoceptor agonists in asthma ‐ help or hindrance. British Journal of Clinical Pharmacology 1992; Vol. 33, issue 2:129‐38. - PMC - PubMed
Lipworth 1997
    1. Lipworth BJ. Airway subsensitivity with long‐acting beta 2‐agonists: is there cause for concern?. Drug Safety 1997;16(5):295‐308. - PubMed
Lipworth 2000
    1. Lipworth BJ, Aziz I. Bronchodilator response to albuterol after regular formoterol and effects of acute corticosteroid administration. Chest 2000; Vol. 117, issue 1:156‐62. - PubMed
McDevitt 1974
    1. McDevitt DG, Shanks RG, Swanton JG. Further observations on cardiotoxicity of isoprenaline during hypoxia. British Journal of Pharmacology 1974; Vol. 50, issue 3:335‐44. - PMC - PubMed
McIvor 1998
    1. McIvor RA, Pizzichini E, Turner MO, Hussack P, Hargreave FE, Sears MR. Potential masking effects of salmeterol on airway inflammation in asthma. American Journal of Respiratory and Critical Care Medicine 1998; Vol. 158, issue 3:924‐30. - PubMed
Morrison 1993
    1. Morrison KJ, Gao Y, Vanhoutte PM. Beta‐adrenoceptors and the epithelial layer in airways. Life Sciences 1993; Vol. 52, issue 26:2123‐30. - PubMed
Nelson 1977
    1. Nelson HS, Raine D, Doner HC, Posey WC. Subsensitivity to bronchodilator action of albuterol produced by chronic administration. American Review of Respiratory Disease 1977; Vol. 116, issue 5:871‐8. - PubMed
Ni Chroinin 2005
    1. Ni Chroinin M, Greenstone IR, Danish A, Magdolinos H, Masse V, Zhang X, et al. Long‐acting beta2‐agonists versus placebo in addition to inhaled corticosteroids in children and adults with chronic asthma. Cochrane Database of Systematic Reviews 2005, Issue 4. [DOI: 10.1002/14651858.CD005535] - DOI - PubMed
Ni Chroinin 2009
    1. Ni Chroinin M, Greenstone IR, Ducharme FM. Addition of long‐acting beta2‐agonists to inhaled steroids as first line therapy for persistent asthma in steroid‐naive adults and children. Cochrane Database of Systematic Reviews 2010, Issue 2. [DOI: 10.1002/14651858.CD005307] - DOI - PubMed
Palmqvist 1999
    1. Palmqvist M, Ibsen T, Mellen A, Lotvall J. Comparison of the relative efficacy of formoterol and salmeterol in asthmatic patients. American Journal of Respiratory and Critical Care Medicine 1999; Vol. 160, issue 1:244‐9. - PubMed
Pearce 1990
    1. Pearce N, Grainger J, Atkinson M, Crane J, Burgess C, Culling C, et al. Case‐control study of prescribed fenoterol and death from asthma in New Zealand, 1977‐81. Thorax 1990; Vol. 45, issue 3:170‐5. - PMC - PubMed
Pearce 2007
    1. Pearce N. Adverse Reactions: the Fenoterol Story. 1. Auckland: Auckland University Press, 2007:215. [ISBN: 9781869403744]
RevMan 2011 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.1. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2011.
Salpeter 2006
    1. Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta‐analysis: effect of long‐acting beta‐agonists on severe asthma exacerbations and asthma‐related deaths. Annals of Internal Medicine 2006;144(12):904‐12. - PubMed
Sears 1986
    1. Sears M, Rea H, Rothwell R, O'Donnell T, Holst P, Gillies A, et al. Asthma mortality: comparison between New Zealand and England. British Medical Journal 1986;293(6558):1342‐5. - PMC - PubMed
Sears 1990
    1. Sears MR, Taylor DR, Print CG, Lake DC, Li QQ, Flannery EM, et al. Regular inhaled beta‐agonist treatment in bronchial‐asthma. Lancet 1990; Vol. 336, issue 8728:1391‐6. - PubMed
SMART 2006
    1. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM, the SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest 2006;129:15‐26. - PubMed
Speizer 1968
    1. Speizer FE, Doll R, Heaf P. Observations on recent increase in mortality from asthma. British Medical Journal 1968; Vol. 1, issue 5588:335‐7. - PMC - PubMed
van der Woude 2001
    1. Woude HJ, Winter TH, Aalbers R. Decreased bronchodilating effect of salbutamol in relieving methacholine induced moderate to severe bronchoconstriction during high dose treatment with long acting beta(2) agonists. Thorax 2001; Vol. 56, issue 7:529‐35. - PMC - PubMed
van Noord 1996
    1. Noord JA, Smeets JJ, Raaijmakers JAM, Bommer AM, Maesen FPV. Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action. European Respiratory Journal 1996; Vol. 9, issue 8:1684‐8. - PubMed
Walters 2002
    1. Walters EH, Walters JAE, Gibson PW. Regular treatment with long acting beta agonists versus daily regular treatment with short acting beta agonists in adults and children with stable asthma. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD003901] - DOI - PMC - PubMed
Walters 2007
    1. Walters EH, Gibson PG, Lasserson TJ, Walters JAE. Long‐acting beta2‐agonists for chronic asthma in adults and children where background therapy contains varied or no inhaled corticosteroid. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD001385.pub2] - DOI - PMC - PubMed
Weber 1982
    1. Weber RW, Smith JA, Nelson HS. Aerosolized terbutaline in asthmatics ‐ development of subsensitivity with long‐term administration. Journal of Allergy and Clinical Immunology 1982; Vol. 70, issue 6:417‐22. - PubMed
Wilson 1981
    1. Wilson JD, Sutherland DC, Thomas AC. Has the change to beta‐agonists combined with oral theophylline increased cases of fatal asthma. Lancet 1981; Vol. 1, issue 8232:1235‐7. - PubMed
Wong 1990
    1. Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE. Bronchodilator, cardiovascular, and hypokalemic effects of fenoterol, salbutamol, and terbutaline in asthma. Lancet 1990; Vol. 336, issue 8728:1396‐9. - PubMed
Yates 1996
    1. Yates DH, Kharitonov SA, Barnes PJ. An inhaled glucocorticoid does not prevent tolerance to the bronchoprotective effect of a long‐acting inhaled beta(2)‐agonist. American Journal of Respiratory and Critical Care Medicine 1996; Vol. 154, issue 6:1603‐7. - PubMed

Publication types