Advertisement

The Indian Journal of Pediatrics

, Volume 67, Issue 2, pp 147–153 | Cite as

Asthma — The changing face of drug therapy

  • Julian Legg
  • John Warner
Symposium: Allergy and Respiratory Disorders-II

Abstract

Until the recent introduction of long acting p2-agonists and the leukotriene antagonists, the drug treatment of asthma had remained largely unchanged for a quarter century. Recent studies have demonstrated the efficacy of the long acting pjagonists in the management of asthma in children and highlighted their value as an adjunct to inhaled corticosteroids. The leukotriene antagonists are an important new class of drug therapy which target a specific area of asthma pathogenesis. Whilst they have been shown to be effective for asthma, their exact role in the clinical situation remains to be established. Recent guidelines have emphasised the important role of inflammation in persistent asthma and recommended the early institution of anti-inflammatory treatment. Many patients remain uncontrolled despite high doses of anti-inflammatory agents including oral corticosteroids. Recent experience with other immunomodulatory agents such as cyclosporin, methotrexate and intravenous immunoglobulin has highlighed their potential as steroid sparing agents.

With improved understanding of asthma pathogenesis the potential for specific targeted therapies has become evident. Monoclonal antibodies to IgE and certain cytokines are being investigated as possible treatments for asthma. Similarly, preliminary studies of selective phosphodiesterase inhibitors in asthmatic individuals have been encouraging. Other potential therapies include platelet-activating factor receptor antagonists, tryptase inhibitors and prostaglandin E analogs. The continued development of such targetea1 treatments should ensure a greater diversity of therapeutic options for the management of asthma in the new millennium.

Key words

Leukotriene antagonists Tryptase inhibitors Asthma 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Burr ML Butland BK, King S, Vaughan-Williams E. Changes in asthma prevalence: two surveys 15 years apart.Arch Dis Child 1989; 64: 1452–1456.PubMedGoogle Scholar
  2. 2.
    Shaw RA, Crane J, O’Donnell TV, Porteous LE, Coleman ED. Increasing asthma prevalence in a rural New Zealand adolescent population: 1975-89Arch Dis Child 1990: 65: 1319–1323.PubMedGoogle Scholar
  3. 3.
    Haahtela T, Lindholm H, Bjorksten F, Koskenvuo K, Laitinen LA. Prevalence of asthma in Finnish young men.BMJ 1990; 301: 266–268.PubMedGoogle Scholar
  4. 4.
    Robertson CF, Heycock E, Bishop J, Nolan T, Olinsky A, Phelan PD. Prevalence of asthma in Melbourne schoolchildren: changes over 26 years.BMJ 1991; 302: 1116–1118.PubMedGoogle Scholar
  5. 5.
    Laor A, Cohen L, Danon YL. Effects of time, sex, ethnic origin, and area of residence on prevalence of asthma in Israeli adolescents.BMJ 1993; 307: 841 -844.PubMedGoogle Scholar
  6. 6.
    Whincup PH, Cook DG, Strachan DP, Papacosta O. Time trends in respiratory symptoms in childhood over a 24 year period.Arch Dis Child 1993; 68: 729–734.PubMedGoogle Scholar
  7. 7.
    Anonymous. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC).Eur Respir J 1998; 12: 315–335.Google Scholar
  8. 8.
    Wood AJJ. Beta-adrenergic bronchodilators.N Engl J Med 1995; 333: 499–506.CrossRefGoogle Scholar
  9. 9.
    Gustaffson PM, vom Berg A, Jenkins MM. Salmeterol 50 meg twice daily in the treatment of mild-to-moderate asthma in childhood — a comparison of two inhalation deyices.Eur J Clin Res 97 A.D.; 5: 63–73.Google Scholar
  10. 10.
    Weinstein SF, Pearlman DS, Bronsky EAet al. Efficacy of salmeterol xinafoate powder in children with chronic persistent asthma.Annals Allergy, Asthma, & Immunol 1998; 81: 51–58.Google Scholar
  11. 11.
    Lenney W, Pedersen S, Boner AL, Ebbutt A, Jenkins MM. Efficacy and safety of salmeterol in childhood asthma.EurJ Pediatr 1995; 154: 983–990.CrossRefGoogle Scholar
  12. 12.
    Verberne AA, Frost C, Roorda FJ, van der Laag H, Kerrebijn KF. One year treatment with salmeterol compared with beclomethasone in children with asthma. The Dutch Paediatric Asthma Study Group.Am J Respir Crit Care Med 1997; 156: 688–695.PubMedGoogle Scholar
  13. 13.
    Russell G, Williams DA, Weller P, Price JF. Salmeterol xinafoate in children on high dose inhaled steroids.Annals Allergy, Asthma, Immunol 1995; 75: 423–428.Google Scholar
  14. 14.
    Verberne AA, Frost C, Duiverman EJ, Grol MH, Kerrebijn KF. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma.Am J Respir Crit Care Med 1998; 158: 213–219.PubMedGoogle Scholar
  15. 15.
    Blake K, Pearlman DS, Scott C, Wang Y, Stahi E, Arledge. Prevention of exercise-induced bronchospasm in pediatric asthma patients; a comparison of salmeterol powder with salbuterol.Annal Allergy, Asthma, Immunol 1999; 82: 205–211.CrossRefGoogle Scholar
  16. 16.
    Bartow RA, Brogden RN. Formoterol. An update of its pharmacological properties and therapeutic efficacy in the management of asthma.Drugs 1998; 55: 303–322.PubMedCrossRefGoogle Scholar
  17. 17.
    De Blic J, Kuusela AL. Formoterol dry powder capsules for inhalation in children with asthma treated over one year [abstract]Eur Respir J 1995; 8: 14.Google Scholar
  18. 18.
    Grainger J, Woodman K, Pearce Net al. Prescribed fenoterol and death from asthma in New Zealand, 1981-7: A further case — control study.Thorax 1996; 46: 105–111.CrossRefGoogle Scholar
  19. 19.
    Cockcroft DW, Swystun VA, Functional antagonism tolerance produced by inhaled beta 2 agonistsThorax 1996; 51: 1051–1056.PubMedGoogle Scholar
  20. 20.
    Woolcock A, Lundback B, Ringdal N, Jacques LA, Comparison of addition of salmeterol to inhaled steroid with doubling of the dose of inhaled steroids.Am J Respir Crit Care Med 1996; 153: 1481–1488.PubMedGoogle Scholar
  21. 21.
    Arledge TE, Liddle R, Stahl E, Rossing TH. Salmeterol does not cause tolerance during long-term asthma therapyJ. AIIergy Clin Immunol 1996; 98: 1116–1119.CrossRefGoogle Scholar
  22. 22.
    British Asthma Guidelines Coordinating Committee. The British guidelines on asthma management 1995 review and position statement.Thorax 1997; 52: S1–21.CrossRefGoogle Scholar
  23. 23.
    National Asthma Education and Prevention Programme. Expert panel report II: guidelines for the diagnosis and management of asthma (USA).Bethesda: NHLBI Information Centre 1997.Google Scholar
  24. 24.
    Feldberg W, Kellaway CH. Liberation of histamine and formation of lycithin like substances by cobra venom.J Physiol 1938; 94: 187–226.PubMedGoogle Scholar
  25. 25.
    Weiss JW, Drazen JM, Coles Net al. Bronchoconstrictor effects of leukotriene C in humans.Science 1982; 216: 196–198.PubMedCrossRefGoogle Scholar
  26. 26.
    Adelroth E, Morris MM, Hargreave FE, O’Byrne PM. Airway responsiveness to leukotrienes C4 and D4 and to methacholine in patients with asthma and normal control.N Engl J Med 1986; 315: 480–484.PubMedCrossRefGoogle Scholar
  27. 27.
    Johnson HG, McNee Ml. Secretogogue responses of leukotriene C4, D4: comparison of potency in canine trachea in vivo.Prostaglandins 1983; 25: 237–243.PubMedCrossRefGoogle Scholar
  28. 28.
    Hui KP, Lotvall J, Chung KF, Barnes PJ. Attenuation of inhaled allergen-induced airway microvascular leakage and airflow obstruction in guinea pigs by a 5-lipoxygenase inhibitor (A-631-162).Am Review Respir Dis 1991; 143: 1015–1019.Google Scholar
  29. 29.
    Munoz NM, Leff AR. Blockade of eosinophil migration by 5-lipoxygenase and cyclooxygenase inhibition in explanted guinea pig trachealis.Am J Physiol 1995; 268: L446-L454.PubMedGoogle Scholar
  30. 30.
    Chung KF. Leukotriene receptor antagonists and biosynthesis inhibitors: potential breakthrough in asthma therapy.Eur Respir J 1995; 8: 1203–1213.PubMedCrossRefGoogle Scholar
  31. 31.
    Israel E, Dermarkarian R, Rosenberg Met al. The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air.N Engl J Med 1993; 199: 1059–1066.Google Scholar
  32. 32.
    Israel E, Rubin P, Kemp JPet al. The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma.Ann Internal Med 1993; 119: 1059–1066.Google Scholar
  33. 33.
    Liu MC, Dube LM, Lancaster J. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group.J Allergy Clin Immunol 1996; 98: 859–871.PubMedCrossRefGoogle Scholar
  34. 34.
    Israel E, Cohn J, Dube L, Drazen JM. Effect of treatment with zileuton, a 5-lipoxygenase inhioitor, in patients with asthma. A randomized controlled trial. Zileuton Clinical Trial Group.JAMA 1996; 275: 931 -936.PubMedCrossRefGoogle Scholar
  35. 35.
    Drazen JM, Israel E, O’Byrne PM. Treatment of asthma with drugs modifying the leukotriene pathway.N Engl J Med 1999;340: 197–206.PubMedCrossRefGoogle Scholar
  36. 36.
    Knorr B, Matz J, Bernstein JA. Montelukast for chronic asthma in 6 to 14 years old children.JAMA 1998; 279: 1181–1186.PubMedCrossRefGoogle Scholar
  37. 37.
    Kemp JP, Dockhorn RJ, Shapiro GGet al. Montelukast once daily inhibits exercise-induced bronchoconstriction in 6 to 14 year old children with asthma.J Pediatr 1998:133: 424–428.PubMedCrossRefGoogle Scholar
  38. 38.
    Kahan BD, Cyclosporine.N Engl J Med 1989; 321: 1725–1738.PubMedCrossRefGoogle Scholar
  39. 39.
    Lagente V, Carre C, Kyriacopoulos F, Boichot E, Mencia-Heurta JM, Braquet P. Inhibitory effect of cyclosporin A on eosinophil infiltration in the guinea-pig lung induced by antigen, platelet activating factor and leukotriene B4.Eur Respir J 1994; 7: 921–926.PubMedGoogle Scholar
  40. 40.
    Alexander AG, Barnes NC, Kay AB. Trial of cyclosporin in the corticosteroid dependant chronic severe asthma.Lancet 1992; 339: 324–328.PubMedCrossRefGoogle Scholar
  41. 41.
    Lock SH, Kay AB, Barnes NC. Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid sparing agent in corticosteroid depedant asthma.Am J Respir Crit Care Med 1996; 153: 509–514.PubMedGoogle Scholar
  42. 42.
    Szczeklik A, Nizankowska E, Dworski R, Domagala B, Pinis. Cyclosporin for steroid depedant asthma.Allergy 1991; 46: 312–315.PubMedCrossRefGoogle Scholar
  43. 43.
    Coren ME, Rosenthal M, Bush A. The use of cyclosporin in corticosteroid dependent asthma.Arch Dis Child 1997: 77: 522–523.PubMedGoogle Scholar
  44. 44.
    Calderon E, Coffey RG, Lockey RF. Mefhotrexate in bronchial asthma.J Allergy Clin Immunol 1991; 88: 274–276.PubMedCrossRefGoogle Scholar
  45. 45.
    Marin MG. Low-dose methotrexate spares steroid usage in steroid-dependant asthmatic patients: a meta-analysis.Chest 1997; 112: 29–33.PubMedGoogle Scholar
  46. 46.
    Stempel DA, Lammert J. Mullarkey MF. Use of methotrexate in the treatment of steroid dependent adolescent asthmatics.Ann Allergy 1991; 67: 346–348.PubMedGoogle Scholar
  47. 47.
    Guss S, Portnoy J. Methotrexate treatment of severe asthma in children.Pediatrics 1992; 89: 635–639.PubMedGoogle Scholar
  48. 48.
    Ballow M. Mechanisms of action of intravenous immune serum globulin therapy.Pediatr Infect Dis J 1994; 13: 806–811.PubMedCrossRefGoogle Scholar
  49. 49.
    Mazer BD, Gelfand EW. An open-label study of high-dose intravenous immunoglobulin in severe childhood asthma.J Allergy Clin Immunol 1991; 87: 976–983.PubMedCrossRefGoogle Scholar
  50. 50.
    Jakobsson T, Croner S, Khellman Nl, Pettersson A, Vassella C, Bjorksten B. Slight steroid sparing effect of intravenous immunoglobulin in children and adolescents with moderately severe bronchial asthma.Allergy 1994; 49: 413–420.PubMedCrossRefGoogle Scholar
  51. 51.
    Niggemann B, Leupold W, Schuster Aet al. Prospective, double-blind, placebo-controlled, multicentre study on the effect of high-dose, intravenous immunoglobulin in children and adolescents with severe bronchial asthma.Clin Expert Allsrgy 1998; 28: 205–210.CrossRefGoogle Scholar
  52. 52.
    Coyle AJ, Wagner K, Bertrand C, Tsuyuki S, Bews J, Heusser C. Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2: cell cytokine production: inhibition by a non-anaphylactogenic anti-lgE antibody.J Exper Med 1996, 183: 1303–1310.CrossRefGoogle Scholar
  53. 53.
    Boulet LP, Chapman KR, Cote Jet al. Inhibitory effect of an anti-lgE antibody E25 on allergen-induced early asthmatic response.Am J Respir Crit Care Med 1997; 155: 1835–1840.PubMedGoogle Scholar
  54. 54.
    Fahy JV, Fleming HE, Wong HHet al. The effect of an anti-lgE monoclonal antibody on the early and late-phase responses to allergen inhalation in asthmatic subjects.Am J Respir Crit Care Med 1997; 155: 1828–1834.PubMedGoogle Scholar
  55. 55.
    Torphy TJ, Phosphodiesterase isozymes, molecular targets for novel antiasthma agents.Am J Respir Crit Care Med 1998; 157: 351 -370.PubMedGoogle Scholar
  56. 56.
    Page CP. Recent advances in our understanding of the use of theophylline in the treatment of asthma.J Clin Pharmacol 1999; 39: 237–240.PubMedGoogle Scholar
  57. 57.
    Harbinson PL, MacLeod D, Hawksworth Ret al. The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen induced responses in asthmatic subjects.Eur Respir J 1997; 10: 1008–1014.PubMedCrossRefGoogle Scholar
  58. 58.
    O’Byrne PM, Wood L. lnterleukin-5 and allergic inflammation.Clin Exper Allergy 1999; 29: 573–575.CrossRefGoogle Scholar
  59. 59.
    Mauser PJ, Pitman AM, Fernandez Xet al. Effects of an antibddy to interleukin-5 in a monkey model of asthma.Am J Respir Crit Care Med 1995; 152: 467–472.PubMedGoogle Scholar
  60. 60.
    Evans DJ, Barnes PJ, Cluzel M, O’Connor BJ. Effects of a potent platelet-activating factor antagonist, SR 27417A, on allergen-induced asthmatic responses.Am J Respir Critical Care Med. 1997; 156: 11 -16.Google Scholar
  61. 61.
    Clark JM, Abraham WM, Fishman CEet al. Tryptase inhibitors block allergen-induced airway and inflammatory responses in allergic sheep.Am J Respir Crit Care Med 1995; 152: 2076–2083.PubMedGoogle Scholar
  62. 62.
    Van Schoor J, Joos GF, Chasson BL, Brouard RJ, Pauwels RA. The effect of the NK2 tachykinin receptor antagonist SR 48968 (Saredutant) on neurokinin A-induced bronchoconstriction in asthmatics.Eur Respir J 1998; 12: 17–23.PubMedCrossRefGoogle Scholar
  63. 63.
    Feldsien D, Sloan S, Wenzel S. Misoprostot, a PGE1 analog, improves the physiologic and inflammatory changes of nocturnal asthma.J Allergy Clin Immunol 1996; 97(1 pt. 3): A687.CrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2000

Authors and Affiliations

  • Julian Legg
    • 1
  • John Warner
    • 1
  1. 1.Institute of Child HealthSouthampton UniversitySouthamptonUK

Personalised recommendations