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PRACTICE: Peter J Barnes Using a combination inhaler (budesonide plus formoterol) as rescue therapy improves asthma control BMJ 2007; 335: 513 [Full text]

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Using a combination inhaler (budesonide plus formoterol) as rescue therapy improves asthma control

Syed F Hussain   (7 September 2007)

A SMART choice for primary care asthma therapy ?

Brian J Lipworth, Catherine Jackson   (13 October 2007)

Using a combination inhaler (budesonide plus formoterol) as rescue therapy improves asthma control 7 September 2007
Syed F Hussain, Consultant Respiratory Physician Kettering General Hospital Send response to journal: Re: Using a combination inhaler (budesonide plus formoterol) as rescue therapy improves asthma control	Recent trials have demonstrated superiority of variable dose of a single combined inhaler in SMART (Symbicort in mainatainance and reliever therapy) therapy compared to stable dose of combined coritcosteroid and long acting bronchodilator therapy plus rescue short acting bronchodilator. At least five studies [1-5]have been published that support the use of budesonide/formoterol in SMART regimen. They have demonstrated longer time to first exacerbation, reduced rate of severe excaerbations, and less inhaled corticosteroid dose though with similar improvement in symptoms, peak flow rates and quality of life in some studies. The concept looks promsing though there are some areas of concern. The main concern is that all the above studies were cunducted by the manufacturing firm (study design, data interpretation, data analysis and publication). Three matching studies from the rival manufacturers of fluticason/salmetrol[6-8] have shown the opposite effect- stable dosing reducing exacerbation rate and improving symptom free days compared to SMART regimen. Secondly in all SMART studies patients needing more than 10 as needed inhalations were excluded and this will have implication on therapy of patients with frequent symptoms. Thirdly there is no convincing evidence that in patients who are well -controlled on stable dose inhaler therapy a change to SMART regimen will be a smart or cost-effective move. In our own limited clinical experience we have found SMART regimen useful in poorly compliant patients and those at the milder spectrum of persistent asthma. Of greater interest was the paper in New England Journal of Medicine and debate on once daily asthma maintainance therapy compared to twice daily regimenns [9]. Certainly, asthma therapy is at the therapeutics crossroads awaiting a change of direction. References 1. Rabe KF, Pizzichini E, Stallberg B et al. Budesonide/ formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial. Chest 2006; 129: 246–56. 2. Rabe KF, Atienza T, Magyar P et al. Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet 2006; 368: 744–53. 3. Vogelmeier C, D’Urzo A, Pauwels R et al. Budesonide/ formoterol maintenance and reliever therapy: an effective asthma treatment option? Eur Respir J 2005; 26: 819–28. 4. O'Byrne PM, Bisgaard H, Godard PP, et al. Budesonide/ Formoterol Combination Therapy as Both Maintenance and Reliever Medication in Asthma. Am J Respir Crit Care 2005;171:129-136. 5. Kuna P, Peters MJ, Manjra AI, et al. Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations. Int J Clin Pract 2007;61:725-736. 6. Price DB, Williams AE, Yoxall S. Salmeterol/fluticasone stable-dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health-related quality of life. Respir Res. 2007;8:46. 7. FitzGerald JM, Boulet LP, Follows RM. The CONCEPT trial: a 1-year, multicenter, randomized,double-blind, double-dummy comparison of a stable dosing regimen of salmeterol/fluticasone propionate with an adjustable maintenance dosing regimen of formoterol/budesonide in adults with persistent asthma. Clin Ther 2005;27(4):393-406. 8. Dahl R, Chuchalin A, Gor D, et al. EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma. Respir Med. 2006 Jul;100(7):1152-62. 9. American Lung Association Asthma Clinical Research Centers, Peters SP, Anthonisen N, Castro M, et al. Randomized comparison of strategies for reducing treatment in mild persistent asthma. N Engl J Med 2007;356(20):2027-39. Competing interests: SFH has received sponsorhips for organising CME program, participation in conferences and speaker fee from Astra Zeneca, GSK and MSD.
A SMART choice for primary care asthma therapy ? 13 October 2007
Brian J Lipworth, Consultant Chest Physician Asthma and Allergy Research Group ,University of Dundee,and Tayside Centre for General Practice, Catherine Jackson Send response to journal: Re: A SMART choice for primary care asthma therapy ?	Professor Barnes makes an apparently cogent argument for using SMART single flexible combination inhaler therapy as the preferred treatment for moderate to severe asthma .Unfortunately his arguments are likely to be rather biased due to the inherent flawed selection criteria used for inclusion into these clinical trials. This is because the SMART trials [and indeed other long acting beta2-agonist trials] selectively exclude patients who are non responders to formoterol, because inclusion requires patients to have demonstrable beta-2-adrenoceptor agonist reversibility . There will always be a heterogeneous response to formoterol due to the predictable development of tolerance ,especially for protection against bronchoconstrictor stimuli ,which may in part be genetically determined [1] .In everyday clinical practice ,especially in primary care ,we do not commonly see such patients who have marked beta-2 agonist reversibility ,as seen in the clinical trials, so it is not possible to extrapolate the results of these studies to what happens out there in the real world . The blanket prescribing of SMART to patients as advocated by Professor Barnes is a slippery slope ,unless perhaps one restricts using the SMART regimen to those who demonstrate beta-2 agonist reversibility ,which is unlikely to happen on a routine basis in the busy setting of primary care ,where most patients with asthma are treated in the UK . The other concern for primary care prescribing is that the routine use of SMART will inevitably creep back in the guidelines from step 3 to step 2 ,whereas most patients with mild to moderate disease can be adequately controlled on an optimised dose of inhaled steroid alone ,which is considerably cheaper . References 1.Lipworth BLong-acting beta(2)-adrenoceptor agonists: a smart choice for asthma? Trends Pharmacol Sci. 2007 Jun;28(6):257-62. Epub 2007 Apr 26 Competing interests: BJL and the Asthma and Allergy Research Group has received payments for performing clinical trials ,educactional support ,equipment ,speaking and consulting from : AstraZeneca ,GlaxoSmithKline,Teva,Mundipharma,Nycomed,Cipla,Neolab,Schering ,Plough,Merck,Trinity-Chiesi,Innovata .