BioDrugs

, Volume 15, Issue 1, pp 11–24 | Cite as

Long-Acting β- Agonist Treatment in Patients with Persistent Asthma Already Receiving Inhaled Corticosteroids

Current Opinion

Abstract

International guidelines recommend that long-acting β-agonists should be considered in patients who are symptomatic despite moderate doses of inhaled corticosteroids. When combined with inhaled corticosteroids they improve asthma symptoms and lung function and reduce exacerbations. The evidence suggests that they are well tolerated. However, they are less effective than inhaled corticosteroids as monotherapy and should not be used alone, although the addition of a long-acting β-agonist may permit a small reduction in the corticosteroid dose. Both salmeterol and formoterol appear equally effective in improving asthma control. Formoterol, however, has a rapid onset of action and is now being promoted for the relief of acute asthma symptoms. Both drugs provide prolonged protection against exercise-induced bronchospasm. However, this effect rapidly diminishes with continuous therapy and if this is the main aim of treatment, intermittent use may be preferable.

When compared with alternative treatments, inhaled long-acting β-agonists are more effective in controlling asthma symptoms than either theophylline or antileukotriene agents. Bambuterol, an oral prodrug of terbutaline, appears to be as effective as the inhaled long-acting β-agonists and has the advantage of once daily oral administration. However, the inhaled long-acting β-agonists are less likely to have systemic adverse effects.

There are theoretical concerns that regular β-agonist treatment may lead to tolerance and a failure to respond to emergency asthma treatment. While there is no doubt that tolerance occurs, there is currently little evidence that this is a clinical problem.

Insights into pharmacological as well as therapeutic interactions between inhaled corticosteroids and β-agonists are providing justification for their use in combination. Guidelines for the management of patients with chronic persistent asthma are likely to require modification to reflect these developments.

References

  1. 1.
    British Thoracic Society. Guidelines on the management of asthma. Thorax 1997; 52 Suppl. 1: S1–21Google Scholar
  2. 2.
    Guidelines for the diagnosis and management of asthma. Publication no. 97-4051. Bethesda: National Institutes for Health, 1997Google Scholar
  3. 3.
    Asthma management handbook 1998. Melbourne: National Asthma Campaign Ltd, 1998Google Scholar
  4. 4.
    Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. NIH/National Heart Lung and Blood Institute; 1995. Publication no.: 95-3659Google Scholar
  5. 5.
    Sont J K, Willems LNA, Bel EH, et al. Clinical control and histopathologic outcome of asthma when using airway hyper-responsiveness as an additional guide to long-term treatment. Am J Respir Crit Care Med 1999; 159: 1043–51PubMedGoogle Scholar
  6. 6.
    Lipworth BJ, Wilson AM. Dose-response to inhaled corticoste-roids: benefits and risks. Semin Respir Crit Care Med 1989; 19: 625–46CrossRefGoogle Scholar
  7. 7.
    Dahl R, Lundback B, Maol JR, et al. A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. Chest 1993; 104: 1352–8PubMedCrossRefGoogle Scholar
  8. 8.
    Pedersen S, Ramsgaard Hansen OR. Budesonide treatment of moderate and severe asthma in children. J Allergy Clin Immunol 1995; 95: 29–33PubMedCrossRefGoogle Scholar
  9. 9.
    Welch MJ, Levy S, Smith JA, et al. Dose-ranging study of the clinical efficacy of twice daily triamcinolone acetonide inhalation aerosol in moderately severe asthma. Chest 1997; 12: 597–606CrossRefGoogle Scholar
  10. 10.
    Busse WW, Brazinsky S, Jacobson K, et al. Efficacy response of inhaled beclomethasone dipropionate in asthma is proportional to dose and is improved by formulation with a new propellant. J Allergy Clin Immunol 1999; 104: 1215–22PubMedCrossRefGoogle Scholar
  11. 11.
    Shapiro G, Bronsky EA, La Force CF, et al. Dose-related efficacy of budesonide administered via a dry powder inhalation in the treatment of children with moderate to severe persistent asthma. J Pediatr 1998; 132: 976–82PubMedCrossRefGoogle Scholar
  12. 12.
    Hummel S, Lehtonen L. Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma. Lancet 1992; 340: 1483–7PubMedCrossRefGoogle Scholar
  13. 13.
    Taylor DR, Sears MR, Cockcroft DW. The beta-agonist controversy. Med Clin North Am 1996; 80: 719–48PubMedCrossRefGoogle Scholar
  14. 14.
    Verberne AAPH, Frost C, Roorda RJ, et al., and the Dutch Paediatric Asthma Study Group. One year treatment with salmeterol compared with beclomethasone in children with asthma. Am J Respir Crit Care Med 1997; 156: 688–95PubMedGoogle Scholar
  15. 15.
    Simons FER, and the Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. N Engl J Med 1997; 337: 1659–65PubMedCrossRefGoogle Scholar
  16. 16.
    Nathan RA, Pinnas JL, Schwartz HJ, et al. A six-month, placebo-controlled comparison of the safety and efficacy of salmeterol or beclomethasone for persistent asthma. Ann Allergy Asthma Immunol 1999; 82: 521–9PubMedCrossRefGoogle Scholar
  17. 17.
    Boyd G, on behalf of a UK study group. Salmeterol xinafoate in asthmatic patients under consideration for maintenance oral corticosteroid therapy. Eur Respir J 1995: 8: 1494–8PubMedGoogle Scholar
  18. 18.
    Russell G, Williams DAJ, Weller P, et al. Salmeterol xinafoate in children on high dose inhaled steroids. Ann Allergy Asthma Immunol 1995; 75: 423–8PubMedGoogle Scholar
  19. 19.
    van der Molen T, Postma DS, Turner MO, et al., on behalf of The Netherlands and Canadian formoterol study investigators. Effects of the long acting β agonist formoterol on asthma control in asthmatic patients using inhaled corticosteroids. Thorax 1996; 52: 535–9CrossRefGoogle Scholar
  20. 20.
    Wilding P, Clark M, Thompson J, et al. Effect of long-term treatment with salmeterol on asthma control: a double-blind, randomised, cross-over study. BMJ 1997; 14: 1441–6CrossRefGoogle Scholar
  21. 21.
    Thomson NC, Angus R, Quebe-Fehling E, et al. Efficacy and tolerability of formoterol in elderly patients with reversible obstructive airways disease. Respir Med 1998; 92: 562–7PubMedCrossRefGoogle Scholar
  22. 22.
    Kemp JP, Cook DA, Incaudo GA, et al. Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroid. J Allergy Clin Immunol 1998; 101: 188–95PubMedCrossRefGoogle Scholar
  23. 23.
    Taylor DR, Town GI, Herbison GP, et al. Asthma control during long-term treatment with regular inhaled salbutamol and salmeterol. Thorax 1998; 53: 744–52PubMedCrossRefGoogle Scholar
  24. 24.
    Akpinarli A, Tuncer A, Saraçlar Y, et al. Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial. Arch Dis Child 1999; 81: 45–8PubMedCrossRefGoogle Scholar
  25. 25.
    Greening AP, Ind PW, Northfield M, et al., on behalf of Allen & Hanburys Ltd UK Study Group. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Lancet 1994; 344: 219–24PubMedCrossRefGoogle Scholar
  26. 26.
    Woolcock A, Lundback B, Ringdal N, et al. Comparison of addition of salmeterol to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit Care Med 1996; 153: 1481–8PubMedGoogle Scholar
  27. 27.
    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: 1405–11PubMedCrossRefGoogle Scholar
  28. 28.
    Verberne AAPH, Frost C, Duiverman EJ, et al. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. Am J Respir Crit Care Med 1998; 158: 213–9PubMedGoogle Scholar
  29. 29.
    Pearlman DS, Stricker W, Weinstein S, et al. Inhaled salmeterol and fluticasone: a study comparing monotherapy and combination therapy in asthma. Ann Allergy Asthma Immunol 1999; 82: 257–65PubMedCrossRefGoogle Scholar
  30. 30.
    Baraniuk J, Murray JJ, Nathan RA, et al. Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma. Chest 1999; 116: 625–32PubMedCrossRefGoogle Scholar
  31. 31.
    Condemi JJ, Goldstein S, Kalberg C, et al., and the Salmeterol Study Group. The addition of salmeterol to fluticasone propi-onate versus increasing the dose of fluticasone propionate in patients with persistent asthma. Ann Allergy Asthma Immunol 1999; 82: 383–9PubMedCrossRefGoogle Scholar
  32. 32.
    Waalkens HJ, van Essen-Zandvliet EE, Hughes MD, et al., and the Dutch CNSLD Study Group. Cessation of long-term treatment with inhaled corticosteroid (budesonide) in children with asthma results in deterioration. Am Rev Respir Dis 1993; 148: 1252–7PubMedGoogle Scholar
  33. 33.
    Gardiner PV, Ward C, Booth H, et al. Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics. Am J Respir Crit Care Med 1994; 150: 1006–11PubMedGoogle Scholar
  34. 34.
    Eickelberg O, Roth M, Lorx 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: 1005–10PubMedCrossRefGoogle Scholar
  35. 35.
    Anenden V, Egemba G, Kessel B. Salmeterol facilitation of fluticasone-induced apoptosis of eosinophils of asthmatics pre- and postantigen challenge. Eur Respir J 1998; 12: 157sGoogle Scholar
  36. 36.
    Nielson CP, Hadjokas NE. Beta-adrenoceptor agonists block corticosteroid inhibition in eosinophils. Am J Respir Crit Care Med 1998; 157: 184–91PubMedGoogle Scholar
  37. 37.
    Peters MJ, Adcock IM, Brown CR, et al. Beta-adrenoreceptor agonists interfere with glucocorticoid receptor DNA binding in rat lung. Eur J Pharmacol 1995; 289: 275–81PubMedCrossRefGoogle Scholar
  38. 38.
    Stevens DA, Barnes PJ, Adcock IM. Beta-agonists inhibit DNA binding of glucocorticoid receptors in human pulmonary and bronchial epithelial cells. Am J Respir Crit Care Med 1995; 151: A195Google Scholar
  39. 39.
    Taylor DR, Hancox RJ. Interactions between corticosteroids and beta-agonists in asthma. Thorax 2000; 55: 595–602PubMedCrossRefGoogle Scholar
  40. 40.
    Hancox RJ, Cowan JO, Flannery EM, et al. A randomised trial of inhaled β2-agonist, inhaled corticosteroid and their combination in the treatment of asthma. Thorax 1999; 54: 482–7PubMedCrossRefGoogle Scholar
  41. 41.
    Aldridge RE, Hancox RJ, Cowan JO, et al. Effects of terbutaline and budesonide on sputum cells and bronchial hyper-responsiveness in asthma. Am J Respir Crit Care Med 2000; 161: 1459–64PubMedGoogle Scholar
  42. 42.
    Spencer CM, Jarvis B. Salmeterol/fluticasone propionate combination. Drugs 1999; 57: 933–40PubMedCrossRefGoogle Scholar
  43. 43.
    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: 1436–41PubMedGoogle Scholar
  44. 44.
    van Noord JA, Smeets JJ, Raaijmakers JAM, et al. Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action. Eur Respir J 1996; 9: 1684–8PubMedCrossRefGoogle Scholar
  45. 45.
    Vervloet D, Ekström T, Pela R, et al. A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease. Respir Med 1998; 92: 836–42PubMedCrossRefGoogle Scholar
  46. 46.
    Rutten-van Mölken MPMH, van Doorslaer EKA, Till MD. Cost-effectiveness analysis of formoterol versus salmeterol in patients with asthma. Pharmacoeconomics 1998; 14: 671–84PubMedCrossRefGoogle Scholar
  47. 47.
    Campbell LM, Anderson TJ, Parashchak MR, et al. A comparison of the efficacy of long-acting β2-agonists: eformoterol via Turbuhaler and salmeterol via pressurised metered dose inhaler or Accuhaler, in mild to moderate asthmatics. Respir Med 1999; 93: 236–44CrossRefGoogle Scholar
  48. 48.
    Palmqvist M, Persson G, Lazer L, et al. Inhaled dry-powder formoterol and salmeterol in asthmatic patients: onset of action, duration of effect and potency. Eur Respir J 1997; 10: 2484–9PubMedCrossRefGoogle Scholar
  49. 49.
    Politiek MJ, Boorsma M, Aalbers R. Comparison of formoterol, salbutamol and salmeterol in methacholine-induced severe bronchoconstriction. Eur Respir J 1999; 13: 988–92PubMedCrossRefGoogle Scholar
  50. 50.
    Ramsdale EH, Otis J, Kline PA, et al. Prolonged protection against methacholine-induced bronchoconstriction by the inhaled β2-agonist formoterol. Am Rev Respir Dis 1991; 143: 998–1001PubMedGoogle Scholar
  51. 51.
    Palmqvist M, Ibsen T, Mellén A, et al. Comparison of the relative efficacy of formoterol and salmeterol in asthmatic patients. Am J Respir Crit Care Med 1999; 160: 244–9PubMedGoogle Scholar
  52. 52.
    Palmqvist M, Balder B, Löwhagen O, et al. Late asthmatic reaction decreased after pretreatment with salbutamol and formoterol, a new long-acting β2-agonist. J Allergy Clin Immunol 1992; 89: 844–9PubMedCrossRefGoogle Scholar
  53. 53.
    Weersink EJM, Aalbers R, Koëter GH, et al. Partial inhibition of the early and late asthmatic reaction by a single dose of salmeterol. Am J Respir Crit Care Med 1994; 150: 1262–7PubMedGoogle Scholar
  54. 54.
    Green CP, Price JF. Prevention of exercise induced asthma by inhaled salmeterol xinafoate. Arch Dis Child 1992; 67: 1014–7PubMedCrossRefGoogle Scholar
  55. 55.
    Kemp JP, Dockhorn Rj, Busse WW, et al. Prolonged effect of inhaled salmeterol against exercise-induced bronchospasm. Am J Respir Crit Care Med 1994; 150: 1612–5PubMedGoogle Scholar
  56. 56.
    Tattersfield A, Löfdahl CG, Postma DS, et al. On demand treatment: comparison of formoterol and terbutaline in moderate asthma. Am J Respir Crit Care Med 1999; 159: A636Google Scholar
  57. 57.
    Malolepszy J, Böszörmény Nagy G, Brander R, et al. Formoterol 90μg via Turbuhaler was safe in patients with acute bronchoconstriction. Eur Respir J 1998; 12: 323sGoogle Scholar
  58. 58.
    Faulds D, Hollingshead LM, Goa KL. Formoterol: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs 1991; 42: 115–37PubMedCrossRefGoogle Scholar
  59. 59.
    Mann RD, Kubota K, Pearce G, et al. Salmeterol: a study by prescription-event monitoring in a UK cohort of 15,407 patients. J Clin Epidemiol 1996; 49: 247–50PubMedCrossRefGoogle Scholar
  60. 60.
    Maconochie JG, Minton NA, Chilton JE, et al. Does tachyphylaxis occur to the non-pulmonary effects of salmeterol? Br J Clin Pharmacol 1994; 37: 199–204PubMedCrossRefGoogle Scholar
  61. 61.
    Cazzola M, Imperotore F, Salzillo A, et al. Cardiac effects of formoterol and salmeterol in patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia. Chest 1998; 114: 411–5PubMedCrossRefGoogle Scholar
  62. 62.
    Sears MR, Taylor DR, Print CG, et al. Regular inhaled beta-agonist treatment in bronchial asthma. Lancet 1990; 336: 1391–6PubMedCrossRefGoogle Scholar
  63. 63.
    Drazen JM, Israel E, Boushey HA, et al. Comparison of regularly scheduled with as-needed use of albuterol in mild asthma. N Engl J Med 1996; 335: 841–7PubMedCrossRefGoogle Scholar
  64. 64.
    Clark CE, Ferguson AD, Siddorn JA. Respiratory arrests in young asthmatics on salmeterol. Respir Med 1993; 87: 227–8PubMedCrossRefGoogle Scholar
  65. 65.
    Castle W, Fuller R, Hall J, et al. Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment. BMJ 1993; 306: 1034–7PubMedCrossRefGoogle Scholar
  66. 66.
    Pearlman DS, Chervinsky P, LaForce C, et al. A comparison of salmeterol with albuterol in the treatment of mild-moderate asthma. N Engl J Med 1992; 327: 1420–5PubMedCrossRefGoogle Scholar
  67. 67.
    D’Alonzo GE, Nathan RA, Henochowicz S, et al. Salmeterol Xinofoate as maintenance therapy compared with albuterol in patients with asthma. JAMA 1994; 271: 1412–6PubMedCrossRefGoogle Scholar
  68. 68.
    Steffensen I, Faurschou P, Riska H, et al. Inhaled formoterol dry powder in the treatment of patients with reversible obstructive airways disease. A 3 month, placebo-controlled comparison of the efficacy and safety of formoterol and salbutamol, followed by a 12 month trial with formoterol. Allergy 1995; 50: 657–63PubMedCrossRefGoogle Scholar
  69. 69.
    Leblanc P, Knight A, Kreisman H, et al. A placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma. Am J Respir Crit Care Med 1996; 154: 324–8PubMedGoogle Scholar
  70. 70.
    Wilkinson JRW, Roberts JA, Bradding P, et al. Paradoxical bronchoconstriction in asthmatic patients after salmeterol by metered-dose inhaler. BMJ 1992; 305: 931–2PubMedCrossRefGoogle Scholar
  71. 71.
    Anon. Salmeterol (Serevent). CurrProbl 1991; No 31Google Scholar
  72. 72.
    McIvor RA, Pizzichini E, Turner MO, et al. Potential masking effects of salmeterol on airway inflammation in asthma. Am J Respir Crit Care Med 1998; 158: 924–30PubMedGoogle Scholar
  73. 73.
    Wong AG, O’Shaughnessy AD, Walker CM, et al. Effects of long-acting and short-acting β-agonists on methacholine dose-response curves in asthmatics. Eur Respir J 1997; 10: 330–6PubMedCrossRefGoogle Scholar
  74. 74.
    Kips JC, O’Connor BJ, Inman MD, et al. A long-term study of the anti-inflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma. Am J Respir Crit Care Med 2000; 161: 996–1001PubMedGoogle Scholar
  75. 75.
    Lanes SF, Lanza LL, Wentworth CE III. Risk of emergency care, hospitalization, and ICU stays for acute asthma among recipients of salmeterol. Am J Respir Crit Care Med 1998; 158: 857–61PubMedGoogle Scholar
  76. 76.
    Williams C, Crossland L, Finnerty J, et al. Case-control study of salmeterol and near-fatal attacks of asthma. Thorax 1998; 53: 7–13PubMedCrossRefGoogle Scholar
  77. 77.
    Barnes PJ. Beta-adrenergic receptors and their regulation. Am J Respir Crit Care Med 1995; 152: 838–60PubMedGoogle Scholar
  78. 78.
    Tattersfield AE. Tolerance to beta agonists. Bull Eur Physiopathol Respir 1985; 21: ls–5sGoogle Scholar
  79. 79.
    Newnham DM, Grove A, McDevitt DG, et al. Subsensitivity of bronchodilator and systemic β2 adrenoreceptor responses after regular twice daily treatment with eformoterol dry powder in asthmatic patients. Thorax 1995; 50: 497–504PubMedCrossRefGoogle Scholar
  80. 80.
    Newnham DM, McDevitt DG, Lipworth BJ. Bronchodilator subsensitivity after chronic dosing with eformoterol in patients with asthma. Am J Med 1994; 97: 29–37PubMedCrossRefGoogle Scholar
  81. 81.
    Yates DH, Sussman HS, Shaw MJ, et al. Regular formoterol treatment in mild asthma: effect on bronchial responsiveness during and after treatment. Am J Respir Crit Care Med 1995; 152: 1170–4PubMedGoogle Scholar
  82. 82.
    Grove A, Lipworth BJ. Bronchodilator subsensitivity to salbutamol after twice daily salmeterol in asthmatic patients. Lancet 1995; 346: 201–6PubMedCrossRefGoogle Scholar
  83. 83.
    Hancox RJ, Aldridge RE, Cowan JO, et al. Tolerance to beta agonists during acute bronchoconstriction. Eur Respir J 1999; 14: 283–7PubMedCrossRefGoogle Scholar
  84. 84.
    Jones SL, Cowan JO, Flannery EM, et al. Bronchodilator tolerance following treatment with formoterol: the effect of acute bronchoconstriction. Eur Respir J. In pressGoogle Scholar
  85. 85.
    Korosec M, Novak RD, Myers E, et al. Salmeterol does not compromise the bronchodilator response to albuterol during acute episodes of asthma. Am J Med 1999; 107: 209–13PubMedCrossRefGoogle Scholar
  86. 86.
    Cockcroft DW, Swystun VA. Functional antagonism: tolerance produced by inhaled β2 agonists. Thorax 1996; 51: 1051–6PubMedCrossRefGoogle Scholar
  87. 87.
    Ramage L, Lipworth BJ, Ingram CG, et al. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Respir Med 1994; 88: 363–8PubMedCrossRefGoogle Scholar
  88. 88.
    Simons FER. Gerstne TV, Cheang MS. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Pediatrics 1997; 99: 655–9PubMedCrossRefGoogle Scholar
  89. 89.
    Drotar DE, Davis EE, Cockcroft DW. Tolerance to the bronchoprotective effect of salmeterol 12 hours after starting twice daily treatment. Ann Allergy Asthma Immunol 1998; 80: 31–4PubMedCrossRefGoogle Scholar
  90. 90.
    Hancox RJ, Cowan JO, Flannery EM, et al. Bronchodilator tolerance and rebound bronchoconstriction during regular inhaled beta-agonist treatment. Respir Med 2000; 94: 767–71PubMedCrossRefGoogle Scholar
  91. 91.
    Yates DH, Kharitonov SA, Barnes PJ. An inhaled glucocorticoid does not prevent tolerance to the bronchoprotective effect of a long-acting inhaled β2-agonist. Am J Respir Crit Care Med 1996; 154: 1603–7PubMedGoogle Scholar
  92. 92.
    Booth H, Bish R, Walters J, et al. Salmeterol tachyphylaxis in steroid treated asthmatic subjects. Thorax 1996; 51: 1100–4PubMedCrossRefGoogle Scholar
  93. 93.
    Crane J, Burgess C. Differential tolerance to β2-adrenoceptor agonists: an alternative hypothesis to explain the asthma paradox. Clin Asthma Rev 1998; 2: 95–101Google Scholar
  94. 94.
    Taylor DR, Drazen JM, Herbison BP, et al. Asthma exacerbations during long-term β-agonist use: influence of β2-adrenoceptor polymorphism. Thorax 2000; 55: 762–8PubMedCrossRefGoogle Scholar
  95. 95.
    Sitar DS. Clinical pharmacokinetics of bambuterol. Clin Pharmacokinet 1996; 31: 246–56PubMedCrossRefGoogle Scholar
  96. 96.
    Petrie GR, Chookang JY, Hassan WU, et al. Bambuterol: effective in nocturnal asthma. Respir Med 1993; 87: 581–5PubMedCrossRefGoogle Scholar
  97. 97.
    D’Alonzo GE, Smolensky MH, Feldman S, et al. Bambuterol in the treatment on asthma: a placebo-controlled comparison on once daily morning vs evening administration. Chest 1995; 107: 406–12PubMedCrossRefGoogle Scholar
  98. 98.
    Fugleholm AM, Ibsen TB, Laxmyr L, et al. Therapeutic equivalence between bambuterol, 10mg once daily, and terbutaline controlled release, 5 mg twice daily, in mild to moderate asthma. Eur Respir J 1993; 6: 1474–8PubMedGoogle Scholar
  99. 99.
    Gunn SD, Ayres JG, McConchie SM, et al. Comparison of the efficacy, tolerability and patient acceptability of once-daily bambuterol tablets against twice-daily controlled release salbutamol in nocturnal asthma. Eur J Clin Pharmacol 1995; 48: 23–8PubMedCrossRefGoogle Scholar
  100. 100.
    McDonald CF, Pierce RJ, Thompson PJ, et al. Comparison of oral bambuterol and terbutaline in elderly patients with chronic reversible airflow obstruction. J Asthma 1997; 34: 53–9PubMedCrossRefGoogle Scholar
  101. 101.
    Kuusela A-L, Marenk M, Sandahl G, et al. Comparative studies using oral solutions of bambuterol once daily or terbutaline three times daily in 2–5-year-old children with asthma. Pediatr Pulmonol 2000; 29: 194–201PubMedCrossRefGoogle Scholar
  102. 102.
    Martin RM, Dunn NR, Freemantle SN, et al. Risk of non-fatal cardiac failure and ischaemic heart disease with long-acting β2 agonists. Thorax 1998; 53: 558–62PubMedCrossRefGoogle Scholar
  103. 103.
    Suissa S, Hemmelgarn B, Biais L, et al. Bronchodilators and acute cardiac death. Am J Respir Crit Care Med 1996; 154: 1598–602PubMedGoogle Scholar
  104. 104.
    Crompton GK, Ayres JG, Basran G, et al. Comparison of oral bambuterol and inhaled salmeterol in patients with symptomatic asthma and using inhaled corticosteroids. Am J Respir Crit Care Med 1999; 159: 824–8PubMedGoogle Scholar
  105. 105.
    Wallaert B, Brun P, Ostinelli J, et al. A comparison of two long-acting beta-agonists, oral bambuterol and inhaled salmeterol, in the treatment of moderate to severe asthmatic patients with nocturnal symptoms. Respir Med 1999; 93: 33–8PubMedCrossRefGoogle Scholar
  106. 106.
    Evans DJ, Taylor DA, Zetterstrom O, et al. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med 1997; 337: 1412–8PubMedCrossRefGoogle Scholar
  107. 107.
    Rabe KF, Dent G. Theophylline and airway inflammation. Clin Exp Allergy 1998; 28 Suppl. 3: 35–41PubMedGoogle Scholar
  108. 108.
    Davies B, Brooks G, Devoy M. The efficacy and safety of salmeterol compared to theophylline: meta-analysis of nine controlled studies. Respir Med 1998; 92: 256–63PubMedCrossRefGoogle Scholar
  109. 109.
    Nutini S, Martini T, Righi R. Long-term treatment of asthmatic patients with salmeterol vs slow-release theophylline. Respir Med 1998; 92: 683–90PubMedCrossRefGoogle Scholar
  110. 110.
    Selby C, Engleman HM, Fitzpatrick MF, et al. Inhaled salmeterol or oral theophylline in nocturnal asthma? Am J Respir Crit Care Med 1997; 155: 104–8PubMedGoogle Scholar
  111. 111.
    Wiegand L, Mende CN, Zaidal G, et al. Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma. Chest 1999; 115: 1525–32PubMedCrossRefGoogle Scholar
  112. 112.
    Lipworth BJ. Leukotriene-receptor antagonists. Lancet 1999; 353: 57–62PubMedCrossRefGoogle Scholar
  113. 113.
    Reiss TF, Chervinsky P, Dockhorn RJ, et al. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of asthma. Arch Intern Med 1998; 158: 1213–20PubMedCrossRefGoogle Scholar
  114. 114.
    Noonan MJ, Chervinsky P, Brandon M, et al. Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in asthma. Eur Respir J 1998; 11: 1232–9PubMedCrossRefGoogle Scholar
  115. 115.
    Busse W, Nelson H, Wolfe J, et al. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. J Allergy Clin Immunol 1999; 103: 1075–80PubMedCrossRefGoogle Scholar
  116. 116.
    Villaran C, O’Neill SJ, Helbling A, et al. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. J Allergy Clin Immunol 1999; 104: 547–53PubMedCrossRefGoogle Scholar
  117. 117.
    Edelman JM, Turpin JA, Bronsky EA, et al. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction. Ann Intern Med 2000; 132: 97–104PubMedGoogle Scholar

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  1. 1.Department of Medical and Surgical SciencesDunedin School of Medicine, University of OtagoDunedinNew Zealand

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