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Combination therapy of long-acting β agonists and inhaled corticosteroids in the management of chronic asthma

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Abstract

Both the Global Initiative for Asthma (GINA) and the National Heart, Lung and Blood Institute (NHLBI) Expert Panel guidelines recommend combination treatment with inhaled corticosteroids (ICSs) and inhaled longacting β-agonists (LABAs) for patients whose asthma is not adequately controlled by low doses of ICSs alone. Not only is this combination more effective than the combination of either theophylline or leukotriene modifiers with ICSs, there is suggestive evidence that the results with LABAs and ICSs may be more than additive. Through the effect of each one on the receptor for the other, they may have a synergistic action. This marked effectiveness of the combination, particularly when combined in the same device, has led to new objectives and novel applications. Therefore, for the first time, it appears that the Goals of Asthma Therapy, as outlined in the guidelines, are achievable for many patients with asthma. Also, at least for combination therapies including formoterol, adjustable dosing and perhaps even use as a rescue as well as a maintenance therapy may be possible.

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References and Recommended Reading

  1. U.S. Department of Health and Human Services, Public Health Service. National Institutes of Health, National Heart Lung and Blood Institute. Global Initiative for Asthma, updated 2003. http://www.ginasthma.com. Accessed December, 2004.

  2. U.S. Department of Health and Human Services, Public Health Service. National Institutes of Health, National Heart Lung and Blood Institute. NAEPP Expert Panel Report. Guidelines for the Diagnosis and Management of Asthma-Update on Selected Topics 2002. NIH Publication No. 02-5075. NHLBI Health Information Network. http://www.nhlbi.nih.gov. Accessed December, 2004.

  3. Bensch G, Lapidus RJ, Levine BE, et al.: A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler. Ann Allergy Asthma Immunol 2001, 86:19–27.

    PubMed  CAS  Google Scholar 

  4. Pearlman DS, Chervinsky P, LaForce C, et al.: A comparison of salmeterol with albuterol in the treatment of mild-tomoderate asthma. N Engl J Med 1992, 327:1420–1425.

    Article  PubMed  CAS  Google Scholar 

  5. Anderson GP: Formoterol: pharmacology, molecular basis of agonism, and mechanism of long duration of a highly potent and selective beta2-adrenoceptor agonist bronchodilator. Life Sci 1993, 52:2145–2160.

    Article  PubMed  CAS  Google Scholar 

  6. Löfdahl C-G: Basic pharmacology of new long-acting sympathomimetics. Lung 1990, 168(Suppl1):18–21.

    PubMed  Google Scholar 

  7. Rabe KF, Jörres R, Nowak D, et al.: Comparison of the effects of salmeterol and formoterol on airway tone and responsiveness over 24 hours in bronchial asthma. Am Rev Respir Dis 1993, 147:1436–1441.

    PubMed  CAS  Google Scholar 

  8. Lazarus SC, Boushey HA, Fahy JV, et al.: Long-acting beta2-agonist monotherapy versus continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomize controlled trail. JAMA 2001, 285:2583–2593.

    Article  PubMed  CAS  Google Scholar 

  9. Taylor DR, Drazen JM, Herbison GP: Asthma exacerbations during long term beta-agonist use: influence of beta 2 adrenoceptor polymorphism. Thorax 2000, 55:762–767.

    Article  PubMed  CAS  Google Scholar 

  10. Allen DB, Bielory L, Derendorf H, et al.: Inhaled corticosteroids: past lessons and future issues. J Allergy Clin Immunol 2003, 112:S1-S40.

    Article  PubMed  CAS  Google Scholar 

  11. Kelly HW: Establishing a therapeutic index for the inhaled corticosteroids: Part I. Pharmacokinetic/pharmacodynamic comparison of the inhaled corticosteroids. J Allergy Clin Immunol 1998, 102:S36-S51.

    Article  PubMed  CAS  Google Scholar 

  12. Petersen H, Kullberg A, Edsbacker S, Greiff L: Nasal retention of budesonide and fluticasone in man: formation of airway mucosal budesonide-esters in vivo. Pharmacol 2001, 51:159–163.

    CAS  Google Scholar 

  13. Martin RJ: Therapeutic significance of distal airway inflammation in asthma. J Allergy Clin Immunol 2002, 109:S447-S460.

    Article  PubMed  Google Scholar 

  14. Agertoft L, Pedersen S: A randomized, double-blind dose reduction study to compare the minimal effective dose of budesonide Tubuhaler and fluticasone propionate Diskhaler. J Allergy Clin Immunol 1998, 101:289–290.

    Article  Google Scholar 

  15. McFadden ER, Casale TB, Edwards TB, et al.: Administration of budesonide once daily by means of Turbuhaler to subjects with stable asthma. J Allergy Clin Immunol 1999, 104:46–52.

    Article  PubMed  CAS  Google Scholar 

  16. Herjavecz I, Blomqvist P, Serrano A: Efficacy of once- and twice-daily administration of budesonide via Turbuhaler as initial therapy in patients with mild persistent asthma. Respir Med 1999, 93:230–235.

    Article  PubMed  CAS  Google Scholar 

  17. Purucker ME, Rosebraugh CJ, Zhou F, Meyer RJ: Inhaled fluticasone propionate by Diskus in the treatment of asthma: a comparison of the efficacy of the same nominal dose given either once or twice a day. Chest 2003, 124:1584–1593.

    Article  PubMed  CAS  Google Scholar 

  18. Greening AP, Ind PW, Northfield M, Shaw G: Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Lancet 1994, 344:219–224.

    Article  PubMed  CAS  Google Scholar 

  19. McIver RA, Pizzichini E, Turner MO, et al.: Potential masking effect of salmeterol on airway inflammation in asthma. Am J Respir Crit Care Med 1998, 158:924–930.

    Google Scholar 

  20. Pauwels RA, Löfdahl C-G, Postma DS, et al.: Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 1997, 337:1405–1411. This was the first study to demonstrate that the addition of an LABA to an ICS reduced both moderate and severe exacerbations of asthma. It also confirmed, in a year long study in a large number of subjects, the previous observations that symptoms as well as pulmonary function was improved by adding LABA to low-dose ICS than, in this case, quadrupling the dose of ICS.

    Article  PubMed  CAS  Google Scholar 

  21. Shrewsbury S, Pyke S, Britton M: Meta-analysis of increased dose of inhaled steroid or addition of salmeterol in symptomatic asthma (MIASMA). Br Med J 2000, 320:1368–1373.

    Article  CAS  Google Scholar 

  22. Eickelberg O, Roth M, Lors R, et al.: Ligand-independent activation of the glucocorticoid receptor by beta2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem 1999, 274:1005–1010.

    Article  PubMed  CAS  Google Scholar 

  23. Nelson HS, Chapman KR, Pyke SD, et al.: Enhanced synergy between fluticasone propionate and salmeterol inhaled from a single inhaler versus separate inhalers. J Allergy Clin Immunol 2003, 112:29–36.

    Article  PubMed  CAS  Google Scholar 

  24. Goldsmith DR, Keating GM: Budesonide/formoterol: a review of its use in asthma. Drugs 2004, 64:1597–1618.

    Article  PubMed  CAS  Google Scholar 

  25. Advair Diskus: Package insert. Research Triangle Park, NC: GlaxoSmithKline. 2004.

  26. Palmqvist M, Arvidsson P, Beckman O, et al.: Onset of bronchodilation of budesonide/formoterol vs salmeterol/fluticasone in single inhalers. Pulm Pharmacol Ther 2001, 14:29–34.

    Article  PubMed  CAS  Google Scholar 

  27. Aalbers R, Backer V, Kava TK, et al.: Adjustable maintenance dosing with budesonide/formoterol compared with fixeddose salmeterol/fluticasone in moderate to severe asthma. Curr Med Res Opin 2004, 20:225–240.

    Article  PubMed  CAS  Google Scholar 

  28. Stoloff SW, Stempel DA, Meyer J, et al.: Improved refill persistence with fluticasone dipropionate and salmeterol in a single inhaler compared with other controller therapies. J Allergy Clin Immunol 2004, 113:245–251. It was thought that the addition of an LABA to an ICS would improve patient adherence to the ICS prescription. This study confirms that subjects refilled their ICS almost twice as often if it was combined in the same device with an LABA rather than the two being prescribed in separate devices.

    Article  PubMed  Google Scholar 

  29. Davies B, Brooks G, Devoy M: The efficacy and safety of salmeterol compared to theophylline: a meta-analysis of nine controlled studies. Respir Med 1998, 92:556–563.

    Google Scholar 

  30. Fish JE, Israel E, Murray JJ, et al.: Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy. Chest 2001, 120:423–430.

    Article  PubMed  CAS  Google Scholar 

  31. Bjermer L, Bustard H, Bouquet J, et al.: Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbations in adults: one year, double blind, randomised, comparative trial. BMJ 2003, 327:891–896.

    Article  PubMed  CAS  Google Scholar 

  32. Ilowite J, Webb R, Friedman B, et al.: Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double blind, multicenter study. Ann Allergy Asthma Immunol 2004, 92:641–648.

    Article  PubMed  CAS  Google Scholar 

  33. Nelson HS, Busse WW, Kerwin E, et al.: Fluticasone propionate/ salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast. J Allergy Clin Immunol 2000, 106:1088–1095.

    Article  PubMed  CAS  Google Scholar 

  34. Ringdal N, Eliraz A, Pruzinec P, et al.: The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. Respir Med 2003, 97:234–241. This study compares the addition of a leukotriene receptor antagonist (LTRA) or an LABA to fluticasone in patients not adequately controlled on low-dose ICS. In this study the combination fluticasone/salmeterol (FSC) inhaler was used. All outcomes favored FSC over adding montelukast to fluticasone, including pulmonary function, symptoms, and rate of asthma exacerbations.

    Article  PubMed  CAS  Google Scholar 

  35. Masoli M, Fabian D, Holt S, Beasley R: The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy 2004, 59:469–478.

    Article  PubMed  Google Scholar 

  36. Bateman ED, Boushey HA, Bousquet J, et al.: Can guidelinedefined asthma control be achieved? The Gaining Optimal Asthma ControL Study. Am J Respir Crit Care Med 2004, 170:836–844.

    Article  PubMed  Google Scholar 

  37. Buhl R, Creemers JPHM, Vondra V, et al.: Once-daily budesonide/ formoterol in a single inhaler in adults with moderate persistent asthma. Respir Med 2003, 97:323–330.

    Article  PubMed  CAS  Google Scholar 

  38. FitzGerald JM, Sears MR, Boulet L-P, et al.: Adjustable maintenance dosing with budesonide/formoterol reduces asthma exacerbations compared with traditional fixed dosing: a fivemonth multicenter Canadian study. Can Respir J 2003, 10:427–434.

    PubMed  Google Scholar 

  39. Ind PW, Haughney J, Price D, et al.: Adjustable and fixed dosing with budesonide/formoterol via a single inhaler in asthma patients: the ASSURE study. Respir Med 2004, 98:464–475.

    Article  PubMed  CAS  Google Scholar 

  40. Boonsawat W, Charoenratanakul S, Pothirat C, et al.: Formoterol (Oxis) Turbuhaler as a rescue therapy compared with salbutamol pMDI plus spacer in patients with acute severe asthma. Respir Med 2003, 97:1067–1074.

    Article  PubMed  CAS  Google Scholar 

  41. Pauwels RA, Sears MR, Campbell M, et al.: Formoterol as relief medication in asthma: a worldwide safety and effectiveness trial. Eur Resp J 2003, 22:787–794.

    Article  CAS  Google Scholar 

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Nelson, H.S. Combination therapy of long-acting β agonists and inhaled corticosteroids in the management of chronic asthma. Curr Allergy Asthma Rep 5, 123–129 (2005). https://doi.org/10.1007/s11882-005-0085-x

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