Skip to main content
SpringerLink
Log in

Oral vs Inhaled Asthma Therapy

Pros, Cons and Combinations

  • Published:
Drugs Aims and scope Submit manuscript

Summary

A number of oral and inhaled drugs are available for the long term management of patients with persistent asthma, yet the disease continues to be associated with significant morbidity and mortality. Over the past years, inhaled glucocorticoids have become established as a cornerstone of maintenance therapy because of their demonstrated clinical efficacy, ability to reduce bronchial inflammation and good tolerability. Other inhaled drugs (e.g. sodium cromoglycate, nedocromil, long-acting β2 agonists) also play a role in the long term treatment of patients with asthma. However, many patients (especially children and the elderly) find inhalers difficult to use, and poor inhalation technique can affect the amount of drug reaching the lungs and response to therapy. Oral drug administration is simple, but, until recently, oral asthma therapy has primarily consisted of sustainedrelease theophylline and glucocorticoids. Theophylline has a narrow therapeutic index, necessitating regular monitoring of serum drug concentrations, and long term oral glucocorticoid therapy is associated with potentially serious adverse events including osteoporosis with bone fracture. The recent development of orally administered leukotriene receptor antagonists (e.g. zafirlukast) and 5-lipoxygenase inhibitors (e.g. zileuton) offers novel mechanisms of action and potential solutions to compliance issues associated with regular administration of inhaled asthma therapy. These drugs have demonstrated efficacy as maintenance therapy in patients with asthma and, importantly, lack the adverse effects associated with long term systemic glucocorticoid therapy. Further clinical trials and the increasing use of these new therapies will help to establish the precise role of orally administered leukotriene receptor antagonists and 5-lipoxygenase inhibitors in the long term management of patients with asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Costello J. Asthma — a United Kingdom view: treatment and implications. Ann NY Acad Sci 1991; 629: 7–14

    Article  PubMed  CAS  Google Scholar 

  2. Sheffer AL. Global initiative for asthma. NHLBI/WHO Workshop report. National Institutes of Health, National Heart, Lung and Blood Institute. Publication no. 95-3659, Jan 1995

  3. Jones K, Bain D, Middleton M, et al. Correlates of asthma morbidity in primary care. BMJ 1992; 304: 361–4

    Article  PubMed  CAS  Google Scholar 

  4. Action Asthma. National Asthma Survey (UK)

  5. Turner-Warwick M. Nocturnal asthma: a study in general practice. J R Coll Gen Pract 1989; 49: 239–44

    Google Scholar 

  6. Sampson A, Costello J. Treatment guidelines for asthma —where will leukotriene receptor antagonists fit in? Pharm J 1995; 255: 26–30

    Google Scholar 

  7. Jain P, Golish JA. Clinical management of asthma in the 1990s: current therapy and new directions. Drugs 1996; 52 Suppl. 6: 1–11

    Article  PubMed  Google Scholar 

  8. Cochrane GM. Compliance and outcomes in patients with asthma. Drugs 1996; 52 Suppl. 6: 12–19

    Article  PubMed  Google Scholar 

  9. Dolovich M. Influence of inhalation technique on response and compliance. Eur Resp Rev 1995; 5: 166–9

    Google Scholar 

  10. Newhouse MT, Dolovich MB. Control of asthma by aerosols. N Engl J Med 1986; 315: 870–4

    Article  PubMed  CAS  Google Scholar 

  11. Allen SC, Prior A. What determines whether an elderly patient can use a metered dose inhaler correctly? Chest 1986; 80: 45–9

    CAS  Google Scholar 

  12. Newhouse MT. Aerosol therapy of asthma in adults and children: role of MDI, DPI, holding chambers and nebulizers. Atemwegs-Lungenkrankh Jahrgang 1994; 20(5) Suppl.: 268–76

    Google Scholar 

  13. Dolovich M, Ruffin RE, Roberts R, et al. Optimal delivery of aerosols from metered-dose inhalers. Chest 1981; 80 Suppl.: S911–5

    Google Scholar 

  14. Newman SP, Pavia D, Garland N, et al. Effects of various inhalation modes on the deposition of radioactive pressurized aerosols. Eur J Respir Dis 1982; 63 Suppl. 119: 57–65

    Google Scholar 

  15. Newman SP, Pavia D, Clarke SW. How should a pressurized beta-adrenergic bronchodilator be inhaled? Eur J Respir Dis 1981; 62: 3–20

    PubMed  CAS  Google Scholar 

  16. Hindle M, Newton DAG, Chrysten H. Investigations of an optimal inhaler technique with the use of urinary excretion as a measure of relative bioavailability to the lung. Thorax 1993; 48: 607–10

    Article  PubMed  CAS  Google Scholar 

  17. Lindgren S, Bake B, Larson S. Clinical consequences of inadequate inhaler technique in asthma therapy. Eur J Respir Dis 1987; 70: 93–8

    PubMed  CAS  Google Scholar 

  18. Isles AF, Robertson CF. Treatment of asthma in children and adolescents: the need for a different approach. Med J Aust 1993; 158: 761–3

    PubMed  CAS  Google Scholar 

  19. Braman SS. Drug treatment of asthma in the elderly. Drugs 1996; 51(3): 415–23

    Article  PubMed  CAS  Google Scholar 

  20. Kelloway JS, Wyatt RA, Adlis SA. Comparison of patients’ compliance with prescribed oral and inhaled asthma medications. Arch Intern Med 1994; 154: 1349–52

    Article  PubMed  CAS  Google Scholar 

  21. Buist AS. Pros and cons of oral anti-asthma medication. Eur Resp Rev 1995; 5: 158–60

    Google Scholar 

  22. Rees J, Price J. Treatment of chronic asthma. BMJ 1995; 310: 1459–63

    Article  PubMed  CAS  Google Scholar 

  23. Brogden RN, Faulds D. Salmeterol xinafoate: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs 1991; 42(5): 895–912

    Article  PubMed  CAS  Google Scholar 

  24. Faulds D, Hollingshead LM, Goa KL. Formoterol: a review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease. Drugs 1991; 42(1): 138–70

    Article  Google Scholar 

  25. Storms WW, Bodman SF, Nathan RA, et al. Use of ipratropium bromide in asthma: results of a multi-clinic study. Am J Med 1986; 81 Suppl. 5A: 61–6

    Article  PubMed  CAS  Google Scholar 

  26. Eisen SA, Miller DK, Woodward RS, et al. The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med 1990; 150: 1331–4

    Article  Google Scholar 

  27. Cramer JA. Commentary. Arch Intern Med 1991; 151: 1236–7

    Article  PubMed  CAS  Google Scholar 

  28. Guidelines on the management of asthma. Thorax 1993; 48 Suppl. 1: S1–24

    Google Scholar 

  29. National Asthma Education Program: guidelines for the diagnosis and management of asthma. Bethesda (MD): National Heart, Lung, and Blood Institute, National Institutes of Health, 1991 Aug: Report no: 91-3042

  30. Adinoff AD, Hollister JR. Steroid-induced fractures and bone loss in patients with asthma. N Engl J Med 1983; 309: 265–8

    Article  PubMed  CAS  Google Scholar 

  31. Dykewicz MS, Greenberger PA, Patterson R, et al. Natural history of asthma in patients requiring long-term systemic corticosteroids. Arch Intern Med 1986; 146: 2369–72

    Article  PubMed  CAS  Google Scholar 

  32. Hosking DJ. Effects of corticosteroids on bone turnover. Respir Med 1993; 87 Suppl. A: 15–21

    Article  PubMed  Google Scholar 

  33. Kwong FK, Sue MA, Klaustermeyer WB. Corticosteroid complications in respiratory disease. Ann Allergy 1987; 58: 326–30

    PubMed  CAS  Google Scholar 

  34. Truhan AP, Ahmed AR. Corticosteroids: a review with emphasis on complications of prolonged systemic therapy. Ann Allergy 1989; 62: 375–90

    PubMed  CAS  Google Scholar 

  35. Sambrook PN, Jones G. Corticosteroid osteoporosis. Br J Rheumatol 1995; 34: 8–12

    Article  PubMed  CAS  Google Scholar 

  36. Laitinen LA, Laitenen A, Haahtela T. A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial. J Allergy Clin Immunol 1992; 90: 32–42

    Article  PubMed  CAS  Google Scholar 

  37. Montefort S, Feather I, Underwood J, et al. The influence of inhaled fluticasone propionate on symptoms, pulmonary physiology and airway inflammation in asthma. Am J Respir Crit Care Med 1995; 151 Suppl.: A40

    Google Scholar 

  38. Trigg CJ, Manolitsas ND, Wang J, et al. Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. Am J Respir Crit Care Med 1994; 150: 17–22

    PubMed  CAS  Google Scholar 

  39. Laursen LC, Taudorf E, Borgeskov S, et al. Fiberoptic bronchoscopy and bronchial mucosal biopsies in asthmatics undergoing long-term high-dose budesonide aerosol treatment. Allergy 1988; 43: 284–8

    Article  PubMed  CAS  Google Scholar 

  40. Booth H, Richmond I, Ward C, et al. Effect of high dose inhaled fluticasone propionate on airway inflammation in asthma. Am J Respir Crit Care Med 1995; 152: 45–52

    PubMed  CAS  Google Scholar 

  41. Djukanovic R, Wilson JW, Britten KM, et al. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis 1992; 145: 669–74

    PubMed  CAS  Google Scholar 

  42. Jeffery PK, Godfrey RW, Adelroth E, et al. Effects of treatment on airway inflammation and thickening of basement membrane reticular collagen in asthma: a quantitative light and electron microscopic study. Am Rev Respir Dis 1992; 145: 890–9

    PubMed  CAS  Google Scholar 

  43. Utiger RD. Differences between inhaled and oral glucocorticoid therapy. N Engl J Med 1993; 329(23): 1731–3

    Article  PubMed  CAS  Google Scholar 

  44. Allegra L. Deliberate non-compliance due to dislike of medications. Eur Resp Rev 1995; 5: 170–2

    Google Scholar 

  45. Adelroth E, Rosenhall L, Johansson S, et al. Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage: the effects of antiasthmatic treatment with budesonide or terbutaline. Am Rev Respir Dis 1990; 142: 91–9

    PubMed  CAS  Google Scholar 

  46. Haahtela T, Jarvinen M, Kava T, et al. Comparison of a beta2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. N Engl J Med 1991; 331: 700–5

    Article  Google Scholar 

  47. Laitinen LA, Laitinen A, Haahtela T. A comparative study of the effects of an inhaled corticosteroid, budesonide, and a beta2-agonist, terbutaline, on airway inflammation in newly diagnosed asthma: a randomized, double-blind, parallel-group controlled trial. J Allergy Clin Immunol 1992; 90: 32–42

    Article  PubMed  CAS  Google Scholar 

  48. van Schayck CP, Dompeling E, van Herwaarden CLA, et al. Bronchodilator treatment in moderate asthma or chronic bronchitis: continuous or on demand? A randomized controlled study. BMJ 1991; 303: 1426–31

    Article  PubMed  Google Scholar 

  49. van Schayck CP, Folgering H, den Otter JJ, et al. Does the continuous use of bronchodilators mask the progression of asthma or chronic bronchitis. Farn Pract 1992; 9: 397–404

    Article  Google Scholar 

  50. Taylor DR, Sears MR, Herbison GP, et al. Regular inhaled beta-agonist in asthma: effects on exacerbations and lung functions. Thorax 1993; 48: 134–8

    Article  PubMed  CAS  Google Scholar 

  51. Chapman KR, Kesten S, Szalai JP. Regular vs as-needed inhaled salbutamol in asthma control. Lancet 1994; 343: 1379–82

    Article  PubMed  CAS  Google Scholar 

  52. Heino M. Regularly inhaled beta-agonists with steroids are not harmful in stable asthma. J Allergy Clin Immunol 1994; 93: 80–4

    Article  PubMed  CAS  Google Scholar 

  53. Wahedna I, Wong CS, Wisniewski AFZ, et al. Asthma control during and after cessation of regular beta2-agonist treatment. Am Rev Respir Dis 1993; 148: 707–12

    Article  PubMed  CAS  Google Scholar 

  54. Beasley R, Burgess C, Pearce N. Confounding by severity does not explain the association between fenoterol and asthma death. Clin Exp Allergy 1994; 24: 660–8

    Article  PubMed  CAS  Google Scholar 

  55. Mullen M-L, Mullen B, Carey M. The association between β-agonist use and death from asthma: a meta-analytic integration of case-control studies. JAMA 1993; 270: 1842–5

    Article  PubMed  CAS  Google Scholar 

  56. Spitzer WO, Suissa S, Ernst P, et al. The use of β-agonists and the risk of death and near death from asthma. N Engl J Med 1992; 326: 501–6

    Article  PubMed  CAS  Google Scholar 

  57. Suissa S, Ernst P, Boivin J-F, et al. A cohort analysis of excess mortality in asthma and the use of inhaled β-agonists. Am J Respir Crit Care Med 1994; 149: 604–10

    PubMed  CAS  Google Scholar 

  58. Britton MG, Earnshaw JS, Palmer JBD, et al. A twelve month comparison of salmeterol with salbutamol in asthmatic patients. Eur Respir J 1993; 5: 1062–7 (Published erratum appears in Eur Respir J 1993; 6: 150)

    Google Scholar 

  59. Kesten S, Chapman KR, Cartier A, et al. A three-months comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma. Am Rev Respir Dis 1991; 144: 622–5

    Article  PubMed  CAS  Google Scholar 

  60. Jones KP on behalf of a UK study group. Salmeterol xinaftoate in the treatment of mild to moderate asthma in primary care. Thorax 1994; 49: 971–5

    Article  PubMed  CAS  Google Scholar 

  61. Pearlman DS, Chervinsky P, La Force C, et al. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med 1992; 327: 1420–5

    Article  PubMed  CAS  Google Scholar 

  62. Gardiner PV, Ward C, Booth H, et al. Effects of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics. Am J Respir Crit Care Med 1994; 150: 1006–11

    PubMed  CAS  Google Scholar 

  63. Roberts JA, Bradding P, Walls AF, et al. The influence of salmeterol xinafoate on mucosal inflammation in asthma. Am Rev Respir Dis 1992; 145 Suppl.: A418

    Google Scholar 

  64. Wong BJ, Dolovich J, Ramsdale EH, et al. Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses. Am Rev Respir Dis 1992; 146: 1156–60

    PubMed  CAS  Google Scholar 

  65. Greening AP, Ind PW, Northfield M, et al. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Lancet 1994; 344: 219–24

    Article  PubMed  CAS  Google Scholar 

  66. 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: 1481–8

    PubMed  CAS  Google Scholar 

  67. Coskey LA, Bitting J, Roth MD. Inhibition of natural killer cell activity by therapeutic levels of theophylline. Am J Resp Cell Mol Biol 1993; 9: 659–65

    CAS  Google Scholar 

  68. Dent G, Giembycz MA, Rabe KF, et al. Theophylline suppresses human alveolar macrophage respiratory burst through phosphodiesterase inhibition. Am J Resp Cell Mol Biol 1994; 10: 565–72

    CAS  Google Scholar 

  69. Djukanovic R, Finnerty JP, Lee C, et al. The effects of theophylline on mucosal inflammation in asthmatic airways: biopsy results. Eur Respir J 1995; 8: 831–3

    PubMed  CAS  Google Scholar 

  70. Kidney JC, Dominguez M, Taylor PM, et al. Immunomodulation by theophylline in asthma: demonstration by withdrawal of therapy. Am J Respir Crit Care Med 1995; 151: 1907–14

    PubMed  CAS  Google Scholar 

  71. Spatafora M, Chiappara G, Merendino AM, et al. Theophylline suppresses the release of tumour necrosis factor-alfa by blood monocytes and alveolar macrophages. Eur Respir J 1994; 7: 223–8

    Article  PubMed  CAS  Google Scholar 

  72. Sullivan PJ, Bekir S, Jaffar Z, et al. The effects of low-dose theophylline on the bronchial wall infiltrate after antigen challenge. Lancet 1993; 343: 1006–8

    Article  Google Scholar 

  73. Ward AJM, McKenniff M, Evans JM, et al. Theophylline: an immunomodulatory role in asthma? Am Rev Respir Dis 1993; 147: 518–23

    PubMed  CAS  Google Scholar 

  74. Weinberger M, Hendeles L. Theophylline in asthma. New Engl J Med 1996; 334: 1380–88

    Article  PubMed  CAS  Google Scholar 

  75. Spector SL, Smith LJ, Glass M, et al. Effects of 6 weeks of therapy with oral doses of ICI 204, 219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. Am J Respir Crit Care Med 1994; 150: 618–23

    PubMed  CAS  Google Scholar 

  76. Lockey RF, Lavins BJ, Snader L. Effects of 13 weeks of treatment with ICI 204,219 (Accolate®) in patients with mild to moderate asthma [abstract no. 839]. J Allergy Clin Immunol 1995 Jan; 95 (Pt 2): 350

    Article  Google Scholar 

  77. Nathan RA, Glass M, Snader L. Effects of 13 weeks of treatment with ICI 204, 219 (Accolate) or cromolyn sodium (Intal) in patients with mild to moderate asthma [abstract no. 990]. J Allergy Clin Immunol 1995 Jan; 388 (Pt 2): 388

    Google Scholar 

  78. Spector SL. Management of asthma with zafirlukast. Clinical experience and tolerability profile. Drugs 1996; 52 Suppl.: 36–46

    Article  PubMed  Google Scholar 

  79. McGill KA, Busse WW. Zileuton. Lancet 1996; 348: 519–24

    Article  PubMed  CAS  Google Scholar 

  80. Brenner M, Berkowitz R, Marshall N, et al. Need for theophylline in severe steroid-requiring asthmatics. Clinical Allergy 1988; 18: 143–50

    Article  PubMed  CAS  Google Scholar 

  81. Nassif EG, Weinberger M, Thompson MS, et al. The value of maintenance theophylline in steroid-dependent asthma. N Engl J Med 1981; 304: 71–5

    Article  PubMed  CAS  Google Scholar 

  82. Fabbri L, Caramori G, Cosma P, et al. Methotrexate in the treatment of systemic glucocorticoid-dependent severe persistent asthma: a word of caution. Monaldi Arch Chest Dis 1996; 51(2): 130–7

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Respiratory and Infectious Diseases, University of Ferrara, Ferrara, Italy

    Leonardo M. Fabbri, Marco Piattella, Gaetano Caramori & Adalberto Ciaccia

Authors
  1. Leonardo M. Fabbri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Piattella
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gaetano Caramori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adalberto Ciaccia
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fabbri, L.M., Piattella, M., Caramori, G. et al. Oral vs Inhaled Asthma Therapy. Drugs 52 (Suppl 6), 20–28 (1996). https://doi.org/10.2165/00003495-199600526-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199600526-00005

Keywords

Search

Navigation