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. 2003 May;79(931):259–267. doi: 10.1136/pmj.79.931.259

Management of asthma in adults: current therapy and future directions

R Green 1, C Brightling 1, I Pavord 1, A Wardlaw 1
PMCID: PMC1742702  PMID: 12782771

Abstract

Asthma is increasing in prevalence worldwide and results in significant use of healthcare resources. Although most patients with asthma can be adequately treated with inhaled corticosteroids, an important number of patients require additional therapy and an increasing number of options are available. A further minority of patients develop severe persistent asthma which remains difficult to manage despite current pharmacological therapies. This review discusses the various treatment options currently available for each stage of asthma severity, highlights some of the limitations of current management, and outlines directions which may improve the management of asthma in the future.

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Selected References

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  1. Aaron S. D., Dales R. E., Pham B. Management of steroid-dependent asthma with methotrexate: a meta-analysis of randomized clinical trials. Respir Med. 1998 Aug;92(8):1059–1065. doi: 10.1016/s0954-6111(98)90355-9. [DOI] [PubMed] [Google Scholar]
  2. Abramson M. J., Puy R. M., Weiner J. M. Allergen immunotherapy for asthma. Cochrane Database Syst Rev. 2000;(2):CD001186–CD001186. doi: 10.1002/14651858.CD001186. [DOI] [PubMed] [Google Scholar]
  3. Adams N. P., Bestall J. B., Jones P. W. Inhaled beclomethasone versus placebo for chronic asthma. Cochrane Database Syst Rev. 2000;(4):CD002738–CD002738. doi: 10.1002/14651858.CD002738. [DOI] [PubMed] [Google Scholar]
  4. Adams N., Bestall J., Jones P. W. Inhaled fluticasone propionate for chronic asthma. Cochrane Database Syst Rev. 2001;(3):CD003135–CD003135. doi: 10.1002/14651858.CD003135. [DOI] [PubMed] [Google Scholar]
  5. Adcock I. M., Caramori G. Cross-talk between pro-inflammatory transcription factors and glucocorticoids. Immunol Cell Biol. 2001 Aug;79(4):376–384. doi: 10.1046/j.1440-1711.2001.01025.x. [DOI] [PubMed] [Google Scholar]
  6. Agertoft L., Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med. 1994 May;88(5):373–381. doi: 10.1016/0954-6111(94)90044-2. [DOI] [PubMed] [Google Scholar]
  7. Allen D. B., Mullen M., Mullen B. A meta-analysis of the effect of oral and inhaled corticosteroids on growth. J Allergy Clin Immunol. 1994 Jun;93(6):967–976. doi: 10.1016/s0091-6749(94)70043-5. [DOI] [PubMed] [Google Scholar]
  8. Anderson S. D., Seale J. P., Rozea P., Bandler L., Theobald G., Lindsay D. A. Inhaled and oral salbutamol in exercise-induced asthma. Am Rev Respir Dis. 1976 Sep;114(3):493–500. doi: 10.1164/arrd.1976.114.3.493. [DOI] [PubMed] [Google Scholar]
  9. Aziz I., Hall I. P., McFarlane L. C., Lipworth B. J. Beta2-adrenoceptor regulation and bronchodilator sensitivity after regular treatment with formoterol in subjects with stable asthma. J Allergy Clin Immunol. 1998 Mar;101(3):337–341. doi: 10.1016/S0091-6749(98)70245-3. [DOI] [PubMed] [Google Scholar]
  10. Barnes P. J., Jonsson B., Klim J. B. The costs of asthma. Eur Respir J. 1996 Apr;9(4):636–642. doi: 10.1183/09031936.96.09040636. [DOI] [PubMed] [Google Scholar]
  11. Bel E. H., Timmers M. C., Hermans J., Dijkman J. H., Sterk P. J. The long-term effects of nedocromil sodium and beclomethasone dipropionate on bronchial responsiveness to methacholine in nonatopic asthmatic subjects. Am Rev Respir Dis. 1990 Jan;141(1):21–28. doi: 10.1164/ajrccm/141.1.21. [DOI] [PubMed] [Google Scholar]
  12. Bernstein I. L., Bernstein D. I., Dubb J. W., Faiferman I., Wallin B. A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma. Auranofin Multicenter Drug Trial. J Allergy Clin Immunol. 1996 Aug;98(2):317–324. doi: 10.1016/s0091-6749(96)70156-2. [DOI] [PubMed] [Google Scholar]
  13. Bjermer L., Bisgaard H., Bousquet J., Fabbri L. M., Greening A., Haahtela T., Holgate S. T., Picado C., Leff J. A. Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rationale of a randomized, double-blind comparative study (the IMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial). Respir Med. 2000 Jun;94(6):612–621. doi: 10.1053/rmed.2000.0806. [DOI] [PubMed] [Google Scholar]
  14. Borish L. C., Nelson H. S., Corren J., Bensch G., Busse W. W., Whitmore J. B., Agosti J. M., IL-4R Asthma Study Group Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol. 2001 Jun;107(6):963–970. doi: 10.1067/mai.2001.115624. [DOI] [PubMed] [Google Scholar]
  15. Borish L. C., Nelson H. S., Lanz M. J., Claussen L., Whitmore J. B., Agosti J. M., Garrison L. Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med. 1999 Dec;160(6):1816–1823. doi: 10.1164/ajrccm.160.6.9808146. [DOI] [PubMed] [Google Scholar]
  16. Boulet L. P., Turcotte H., Boutet M., Montminy L., Laviolette M. Influence of natural antigenic exposure on expiratory flows, methacholine responsiveness, and airway inflammation in mild allergic asthma. J Allergy Clin Immunol. 1993 Apr;91(4):883–893. doi: 10.1016/0091-6749(93)90346-h. [DOI] [PubMed] [Google Scholar]
  17. Brightling Christopher E., Bradding Peter, Symon Fiona A., Holgate Stephen T., Wardlaw Andrew J., Pavord Ian D. Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med. 2002 May 30;346(22):1699–1705. doi: 10.1056/NEJMoa012705. [DOI] [PubMed] [Google Scholar]
  18. British Thoracic Society. Scottish Intercollegiate Guidelines Network British guideline on the management of asthma. Thorax. 2003 Feb;58 (Suppl 1):i1–94. doi: 10.1136/thorax.58.suppl_1.1i. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Brown P. H., Blundell G., Greening A. P., Crompton G. K. Do large volume spacer devices reduce the systemic effects of high dose inhaled corticosteroids? Thorax. 1990 Oct;45(10):736–739. doi: 10.1136/thx.45.10.736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Bryan S. A., O'Connor B. J., Matti S., Leckie M. J., Kanabar V., Khan J., Warrington S. J., Renzetti L., Rames A., Bock J. A. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000 Dec 23;356(9248):2149–2153. doi: 10.1016/S0140-6736(00)03497-8. [DOI] [PubMed] [Google Scholar]
  21. Busse W., Corren J., Lanier B. Q., McAlary M., Fowler-Taylor A., Cioppa G. D., van As A., Gupta N. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001 Aug;108(2):184–190. doi: 10.1067/mai.2001.117880. [DOI] [PubMed] [Google Scholar]
  22. Cates C. J., Rowe B. H., Bara A. Holding chambers versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2002;(2):CD000052–CD000052. doi: 10.1002/14651858.CD000052. [DOI] [PubMed] [Google Scholar]
  23. Chalmers G. W., Macleod K. J., Little S. A., Thomson L. J., McSharry C. P., Thomson N. C. Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma. Thorax. 2002 Mar;57(3):226–230. doi: 10.1136/thorax.57.3.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Chan-Yeung M., Manfreda J., Dimich-Ward H., Ferguson A., Watson W., Becker A. A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants. Arch Pediatr Adolesc Med. 2000 Jul;154(7):657–663. doi: 10.1001/archpedi.154.7.657. [DOI] [PubMed] [Google Scholar]
  25. Clark D. J., Lipworth B. J. Adrenal suppression with chronic dosing of fluticasone propionate compared with budesonide in adult asthmatic patients. Thorax. 1997 Jan;52(1):55–58. doi: 10.1136/thx.52.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Custovic A., Simpson B. M., Simpson A., Kissen P., Woodcock A., NAC Manchester Asthma and Allergy Study Group Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial. Lancet. 2001 Jul 21;358(9277):188–193. doi: 10.1016/S0140-6736(01)05406-X. [DOI] [PubMed] [Google Scholar]
  27. Dahl R., Lundback B., Malo J. L., Mazza J. A., Nieminen M. M., Saarelainen P., Barnacle H. A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. International Study Group. Chest. 1993 Nov;104(5):1352–1358. doi: 10.1378/chest.104.5.1352. [DOI] [PubMed] [Google Scholar]
  28. Dennis S. M., Sharp S. J., Vickers M. R., Frost C. D., Crompton G. K., Barnes P. J., Lee T. H. Regular inhaled salbutamol and asthma control: the TRUST randomised trial. Therapy Working Group of the National Asthma Task Force and the MRC General Practice Research Framework. Lancet. 2000 May 13;355(9216):1675–1679. doi: 10.1016/s0140-6736(00)02238-8. [DOI] [PubMed] [Google Scholar]
  29. Derendorf H., Hochhaus G., Meibohm B., Möllmann H., Barth J. Pharmacokinetics and pharmacodynamics of inhaled corticosteroids. J Allergy Clin Immunol. 1998 Apr;101(4 Pt 2):S440–S446. doi: 10.1016/s0091-6749(98)70156-3. [DOI] [PubMed] [Google Scholar]
  30. Dewar J. C., Wheatley A. P., Venn A., Morrison J. F., Britton J., Hall I. P. Beta2-adrenoceptor polymorphisms are in linkage disequilibrium, but are not associated with asthma in an adult population. Clin Exp Allergy. 1998 Apr;28(4):442–448. doi: 10.1046/j.1365-2222.1998.00245.x. [DOI] [PubMed] [Google Scholar]
  31. Diamant Z., Grootendorst D. C., Veselic-Charvat M., Timmers M. C., De Smet M., Leff J. A., Seidenberg B. C., Zwinderman A. H., Peszek I., Sterk P. J. The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist, on allergen-induced airway responses and sputum cell counts in asthma. Clin Exp Allergy. 1999 Jan;29(1):42–51. doi: 10.1046/j.1365-2222.1999.00447.x. [DOI] [PubMed] [Google Scholar]
  32. Diaz P., Galleguillos F. R., Gonzalez M. C., Pantin C. F., Kay A. B. Bronchoalveolar lavage in asthma: the effect of disodium cromoglycate (cromolyn) on leukocyte counts, immunoglobulins, and complement. J Allergy Clin Immunol. 1984 Jul;74(1):41–48. doi: 10.1016/0091-6749(84)90085-x. [DOI] [PubMed] [Google Scholar]
  33. Djukanović R., Wilson J. W., Britten K. M., Wilson S. J., Walls A. F., Roche W. R., Howarth P. H., Holgate S. T. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. 1992 Mar;145(3):669–674. doi: 10.1164/ajrccm/145.3.669. [DOI] [PubMed] [Google Scholar]
  34. Djukanović R., Wilson J. W., Britten K. M., Wilson S. J., Walls A. F., Roche W. R., Howarth P. H., Holgate S. T. Effect of an inhaled corticosteroid on airway inflammation and symptoms in asthma. Am Rev Respir Dis. 1992 Mar;145(3):669–674. doi: 10.1164/ajrccm/145.3.669. [DOI] [PubMed] [Google Scholar]
  35. Donahue J. G., Weiss S. T., Livingston J. M., Goetsch M. A., Greineder D. K., Platt R. Inhaled steroids and the risk of hospitalization for asthma. JAMA. 1997 Mar 19;277(11):887–891. [PubMed] [Google Scholar]
  36. Drazen J. M., Yandava C. N., Dubé L., Szczerback N., Hippensteel R., Pillari A., Israel E., Schork N., Silverman E. S., Katz D. A. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999 Jun;22(2):168–170. doi: 10.1038/9680. [DOI] [PubMed] [Google Scholar]
  37. Ducharme Francine M. Anti-leukotrienes as add-on therapy to inhaled glucocorticoids in patients with asthma: systematic review of current evidence. BMJ. 2002 Jun 29;324(7353):1545–1545. doi: 10.1136/bmj.324.7353.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Edwards A. M. Sodium cromoglycate (Intal) as an anti-inflammatory agent for the treatment of chronic asthma. Clin Exp Allergy. 1994 Jul;24(7):612–623. doi: 10.1111/j.1365-2222.1994.tb00964.x. [DOI] [PubMed] [Google Scholar]
  39. Evans D. J., Taylor D. A., Zetterstrom O., Chung K. F., O'Connor B. J., Barnes P. J. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med. 1997 Nov 13;337(20):1412–1418. doi: 10.1056/NEJM199711133372002. [DOI] [PubMed] [Google Scholar]
  40. Finnerty J. P., Wood-Baker R., Thomson H., Holgate S. T. Role of leukotrienes in exercise-induced asthma. Inhibitory effect of ICI 204219, a potent leukotriene D4 receptor antagonist. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):746–749. doi: 10.1164/ajrccm/145.4_Pt_1.746. [DOI] [PubMed] [Google Scholar]
  41. Fish J. E., Israel E., Murray J. J., Emmett A., Boone R., Yancey S. W., Rickard K. A. Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy. Chest. 2001 Aug;120(2):423–430. doi: 10.1378/chest.120.2.423. [DOI] [PubMed] [Google Scholar]
  42. Gibson P. G., Coughlan J., Wilson A. J., Abramson M., Bauman A., Hensley M. J., Walters E. H. Self-management education and regular practitioner review for adults with asthma. Cochrane Database Syst Rev. 2000;(2):CD001117–CD001117. doi: 10.1002/14651858.CD001117. [DOI] [PubMed] [Google Scholar]
  43. Green Ruth H., Brightling Christopher E., McKenna Susan, Hargadon Beverley, Parker Debbie, Bradding Peter, Wardlaw Andrew J., Pavord Ian D. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002 Nov 30;360(9347):1715–1721. doi: 10.1016/S0140-6736(02)11679-5. [DOI] [PubMed] [Google Scholar]
  44. Greening A. P., Ind P. W., Northfield M., Shaw G. Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group. Lancet. 1994 Jul 23;344(8917):219–224. doi: 10.1016/s0140-6736(94)92996-3. [DOI] [PubMed] [Google Scholar]
  45. Grove A., Lipworth B. J. Bronchodilator subsensitivity to salbutamol after twice daily salmeterol in asthmatic patients. Lancet. 1995 Jul 22;346(8969):201–206. doi: 10.1016/s0140-6736(95)91265-7. [DOI] [PubMed] [Google Scholar]
  46. Gøtzsche P. C., Johansen H. K., Hammarquist C., Burr M. L. House dust mite control measures for asthma. Cochrane Database Syst Rev. 2001;(2):CD001187–CD001187. doi: 10.1002/14651858.CD001187. [DOI] [PubMed] [Google Scholar]
  47. Haahtela T., Järvinen M., Kava T., Kiviranta K., Koskinen S., Lehtonen K., Nikander K., Persson T., Reinikainen K., Selroos O. Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. N Engl J Med. 1991 Aug 8;325(6):388–392. doi: 10.1056/NEJM199108083250603. [DOI] [PubMed] [Google Scholar]
  48. Hancox R. J., Sears M. R., Taylor D. R. Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma. Eur Respir J. 1998 Mar;11(3):589–593. [PubMed] [Google Scholar]
  49. Hunter Cameron J., Brightling Christopher E., Woltmann Gerrit, Wardlaw Andrew J., Pavord Ian D. A comparison of the validity of different diagnostic tests in adults with asthma. Chest. 2002 Apr;121(4):1051–1057. doi: 10.1378/chest.121.4.1051. [DOI] [PubMed] [Google Scholar]
  50. Israel E., Drazen J. M., Liggett S. B., Boushey H. A., Cherniack R. M., Chinchilli V. M., Cooper D. M., Fahy J. V., Fish J. E., Ford J. G. The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med. 2000 Jul;162(1):75–80. doi: 10.1164/ajrccm.162.1.9907092. [DOI] [PubMed] [Google Scholar]
  51. Jamison J. P., McKinley R. K. Validity of peak expiratory flow rate variability for the diagnosis of asthma. Clin Sci (Lond) 1993 Sep;85(3):367–371. doi: 10.1042/cs0850367. [DOI] [PubMed] [Google Scholar]
  52. Jatakanon A., Kharitonov S., Lim S., Barnes P. J. Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma. Thorax. 1999 Feb;54(2):108–114. doi: 10.1136/thx.54.2.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Jones A., Pill R., Adams S. Qualitative study of views of health professionals and patients on guided self management plans for asthma. BMJ. 2000 Dec 16;321(7275):1507–1510. doi: 10.1136/bmj.321.7275.1507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Kennedy W. A., Laurier C., Gautrin D., Ghezzo H., Paré M., Malo J. L., Contandriopoulos A. P. Occurrence and risk factors of oral candidiasis treated with oral antifungals in seniors using inhaled steroids. J Clin Epidemiol. 2000 Jul;53(7):696–701. doi: 10.1016/s0895-4356(99)00191-2. [DOI] [PubMed] [Google Scholar]
  55. Kesten S., Chapman K. R., Broder I., Cartier A., Hyland R. H., Knight A., Malo J. L., Mazza J. A., Moote D. W., Small P. A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma. Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):622–625. doi: 10.1164/ajrccm/144.3_Pt_1.622. [DOI] [PubMed] [Google Scholar]
  56. Lazarus S. C., Boushey H. A., Fahy J. V., Chinchilli V. M., Lemanske R. F., Jr, Sorkness C. A., Kraft M., Fish J. E., Peters S. P., Craig T. Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. JAMA. 2001 May 23;285(20):2583–2593. doi: 10.1001/jama.285.20.2583. [DOI] [PubMed] [Google Scholar]
  57. Leckie M. J., ten Brinke A., Khan J., Diamant Z., O'Connor B. J., Walls C. M., Mathur A. K., Cowley H. C., Chung K. F., Djukanovic R. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000 Dec 23;356(9248):2144–2148. doi: 10.1016/s0140-6736(00)03496-6. [DOI] [PubMed] [Google Scholar]
  58. Leff J. A., Busse W. W., Pearlman D., Bronsky E. A., Kemp J., Hendeles L., Dockhorn R., Kundu S., Zhang J., Seidenberg B. C. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med. 1998 Jul 16;339(3):147–152. doi: 10.1056/NEJM199807163390302. [DOI] [PubMed] [Google Scholar]
  59. Lim S., Jatakanon A., Gordon D., Macdonald C., Chung K. F., Barnes P. J. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice. Thorax. 2000 Oct;55(10):837–841. doi: 10.1136/thorax.55.10.837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Lima J. J., Thomason D. B., Mohamed M. H., Eberle L. V., Self T. H., Johnson J. A. Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics. Clin Pharmacol Ther. 1999 May;65(5):519–525. doi: 10.1016/S0009-9236(99)70071-8. [DOI] [PubMed] [Google Scholar]
  61. Lipworth B. J., Dempsey O. J., Aziz I., Wilson A. M. Effects of adding a leukotriene antagonist or a long-acting beta(2)-agonist in asthmatic patients with the glycine-16 beta(2)-adrenoceptor genotype. Am J Med. 2000 Aug 1;109(2):114–121. doi: 10.1016/s0002-9343(00)00454-x. [DOI] [PubMed] [Google Scholar]
  62. Lock S. H., Kay A. B., Barnes N. C. Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma. Am J Respir Crit Care Med. 1996 Feb;153(2):509–514. doi: 10.1164/ajrccm.153.2.8564089. [DOI] [PubMed] [Google Scholar]
  63. Löfdahl C. G., Reiss T. F., Leff J. A., Israel E., Noonan M. J., Finn A. F., Seidenberg B. C., Capizzi T., Kundu S., Godard P. Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. BMJ. 1999 Jul 10;319(7202):87–90. doi: 10.1136/bmj.319.7202.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Mahajan P., Okamoto L. J., Schaberg A., Kellerman D., Schoenwetter W. F. Impact of fluticasone propionate powder on health-related quality of life in patients with moderate asthma. J Asthma. 1997;34(3):227–234. doi: 10.3109/02770909709068193. [DOI] [PubMed] [Google Scholar]
  65. Mak V. H., Melchor R., Spiro S. G. Easy bruising as a side-effect of inhaled corticosteroids. Eur Respir J. 1992 Oct;5(9):1068–1074. [PubMed] [Google Scholar]
  66. Manning P. J., Watson R. M., Margolskee D. J., Williams V. C., Schwartz J. I., O'Byrne P. M. Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist. N Engl J Med. 1990 Dec 20;323(25):1736–1739. doi: 10.1056/NEJM199012203232504. [DOI] [PubMed] [Google Scholar]
  67. McGraw D. W., Forbes S. L., Kramer L. A., Liggett S. B. Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression. J Clin Invest. 1998 Dec 1;102(11):1927–1932. doi: 10.1172/JCI4862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Nathan R. A., Li J. T., Finn A., Jones R., Payne J. E., Wolford J. P., Harding S. M. A dose-ranging study of fluticasone propionate administered once daily via multidose powder inhaler to patients with moderate asthma. Chest. 2000 Aug;118(2):296–302. doi: 10.1378/chest.118.2.296. [DOI] [PubMed] [Google Scholar]
  69. Nelson H. S. Beta-adrenergic bronchodilators. N Engl J Med. 1995 Aug 24;333(8):499–506. doi: 10.1056/NEJM199508243330807. [DOI] [PubMed] [Google Scholar]
  70. Nelson H. S., Busse W. W., Kerwin E., Church N., Emmett A., Rickard K., Knobil K. Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast. J Allergy Clin Immunol. 2000 Dec;106(6):1088–1095. doi: 10.1067/mai.2000.110920. [DOI] [PubMed] [Google Scholar]
  71. Neville R. G., Pearson M. G., Richards N., Patience J., Sondhi S., Wagstaff B., Wells N. A cost analysis on the pattern of asthma prescribing in the UK. Eur Respir J. 1999 Sep;14(3):605–609. doi: 10.1034/j.1399-3003.1999.14c20.x. [DOI] [PubMed] [Google Scholar]
  72. Newnham D. M., Grove A., McDevitt D. G., Lipworth B. J. Subsensitivity of bronchodilator and systemic beta 2 adrenoceptor responses after regular twice daily treatment with eformoterol dry powder in asthmatic patients. Thorax. 1995 May;50(5):497–504. doi: 10.1136/thx.50.5.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. O'Byrne P. M., Barnes P. J., Rodriguez-Roisin R., Runnerstrom E., Sandstrom T., Svensson K., Tattersfield A. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med. 2001 Oct 15;164(8 Pt 1):1392–1397. doi: 10.1164/ajrccm.164.8.2104102. [DOI] [PubMed] [Google Scholar]
  74. O'Connor B. J., Aikman S. L., Barnes P. J. Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma. N Engl J Med. 1992 Oct 22;327(17):1204–1208. doi: 10.1056/NEJM199210223271704. [DOI] [PubMed] [Google Scholar]
  75. Pauwels R. A., Löfdahl C. G., Postma D. S., Tattersfield A. E., O'Byrne P., Barnes P. J., Ullman A. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997 Nov 13;337(20):1405–1411. doi: 10.1056/NEJM199711133372001. [DOI] [PubMed] [Google Scholar]
  76. Pavord I. D., Brightling C. E., Woltmann G., Wardlaw A. J. Non-eosinophilic corticosteroid unresponsive asthma. Lancet. 1999 Jun 26;353(9171):2213–2214. doi: 10.1016/S0140-6736(99)01813-9. [DOI] [PubMed] [Google Scholar]
  77. Pearlman D. S., Chervinsky P., LaForce C., Seltzer J. M., Southern D. L., Kemp J. P., Dockhorn R. J., Grossman J., Liddle R. F., Yancey S. W. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. N Engl J Med. 1992 Nov 12;327(20):1420–1425. doi: 10.1056/NEJM199211123272004. [DOI] [PubMed] [Google Scholar]
  78. Pizzichini E., Leff J. A., Reiss T. F., Hendeles L., Boulet L. P., Wei L. X., Efthimiadis A. E., Zhang J., Hargreave F. E. Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial. Eur Respir J. 1999 Jul;14(1):12–18. doi: 10.1034/j.1399-3003.1999.14a04.x. [DOI] [PubMed] [Google Scholar]
  79. Pizzichini M. M., Pizzichini E., Clelland L., Efthimiadis A., Pavord I., Dolovich J., Hargreave F. E. Prednisone-dependent asthma: inflammatory indices in induced sputum. Eur Respir J. 1999 Jan;13(1):15–21. doi: 10.1183/09031936.99.13101599. [DOI] [PubMed] [Google Scholar]
  80. Pollard S. J., Spector S. L., Yancey S. W., Cox F. M., Emmett A. Salmeterol versus theophylline in the treatment of asthma. Ann Allergy Asthma Immunol. 1997 May;78(5):457–464. doi: 10.1016/S1081-1206(10)63232-2. [DOI] [PubMed] [Google Scholar]
  81. Ram F. S., Robinson S. M., Black P. N. Physical training for asthma. Cochrane Database Syst Rev. 2000;(2):CD001116–CD001116. doi: 10.1002/14651858.CD001116. [DOI] [PubMed] [Google Scholar]
  82. Reiss T. F., Sorkness C. A., Stricker W., Botto A., Busse W. W., Kundu S., Zhang J. Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. Thorax. 1997 Jan;52(1):45–48. doi: 10.1136/thx.52.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Sampson A. P., Siddiqui S., Buchanan D., Howarth P. H., Holgate S. T., Holloway J. W., Sayers I. Variant LTC(4) synthase allele modifies cysteinyl leukotriene synthesis in eosinophils and predicts clinical response to zafirlukast. Thorax. 2000 Oct;55 (Suppl 2):S28–S31. doi: 10.1136/thorax.55.suppl_2.S28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Selroos O., Halme M. Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler. Thorax. 1991 Dec;46(12):891–894. doi: 10.1136/thx.46.12.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Siroux V., Pin I., Oryszczyn M. P., Le Moual N., Kauffmann F. Relationships of active smoking to asthma and asthma severity in the EGEA study. Epidemiological study on the Genetics and Environment of Asthma. Eur Respir J. 2000 Mar;15(3):470–477. doi: 10.1034/j.1399-3003.2000.15.08.x. [DOI] [PubMed] [Google Scholar]
  86. Solèr M., Matz J., Townley R., Buhl R., O'Brien J., Fox H., Thirlwell J., Gupta N., Della Cioppa G. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001 Aug;18(2):254–261. doi: 10.1183/09031936.01.00092101. [DOI] [PubMed] [Google Scholar]
  87. Spector S. L., Smith L. J., Glass M. Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. ACCOLATE Asthma Trialists Group. Am J Respir Crit Care Med. 1994 Sep;150(3):618–623. doi: 10.1164/ajrccm.150.3.8087328. [DOI] [PubMed] [Google Scholar]
  88. Suissa S., Ernst P., Benayoun S., Baltzan M., Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med. 2000 Aug 3;343(5):332–336. doi: 10.1056/NEJM200008033430504. [DOI] [PubMed] [Google Scholar]
  89. Suissa S., Ernst P., Boivin J. F., Horwitz R. I., Habbick B., Cockroft D., Blais L., McNutt M., Buist A. S., Spitzer W. O. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):604–610. doi: 10.1164/ajrccm.149.3.8118625. [DOI] [PubMed] [Google Scholar]
  90. Sullivan P., Bekir S., Jaffar Z., Page C., Jeffery P., Costello J. Anti-inflammatory effects of low-dose oral theophylline in atopic asthma. Lancet. 1994 Apr 23;343(8904):1006–1008. doi: 10.1016/s0140-6736(94)90127-9. [DOI] [PubMed] [Google Scholar]
  91. Szefler S. J., Nelson H. S. Alternative agents for anti-inflammatory treatment of asthma. J Allergy Clin Immunol. 1998 Oct;102(4 Pt 2):S23–S35. doi: 10.1016/s0091-6749(98)70003-x. [DOI] [PubMed] [Google Scholar]
  92. Tan S., Hall I. P., Dewar J., Dow E., Lipworth B. Association between beta 2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics. Lancet. 1997 Oct 4;350(9083):995–999. doi: 10.1016/S0140-6736(97)03211-X. [DOI] [PubMed] [Google Scholar]
  93. Taylor I. K., O'Shaughnessy K. M., Fuller R. W., Dollery C. T. Effect of cysteinyl-leukotriene receptor antagonist ICI 204.219 on allergen-induced bronchoconstriction and airway hyperreactivity in atopic subjects. Lancet. 1991 Mar 23;337(8743):690–694. doi: 10.1016/0140-6736(91)90277-v. [DOI] [PubMed] [Google Scholar]
  94. Thomas M., McKinley R. K., Freeman E., Foy C. Prevalence of dysfunctional breathing in patients treated for asthma in primary care: cross sectional survey. BMJ. 2001 May 5;322(7294):1098–1100. doi: 10.1136/bmj.322.7294.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Thomas M., McKinley R. K., Freeman E., Foy C., Prodger P., Price D. Breathing retraining for dysfunctional breathing in asthma: a randomised controlled trial. Thorax. 2003 Feb;58(2):110–115. doi: 10.1136/thorax.58.2.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Turner M. O., Johnston P. R., Pizzichini E., Pizzichini M. M., Hussack P. A., Hargreave F. E. Anti-inflammatory effects of salmeterol compared with beclomethasone in eosinophilic mild exacerbations of asthma: a randomized, placebo controlled trial. Can Respir J. 1998 Jul-Aug;5(4):261–268. doi: 10.1155/1998/868379. [DOI] [PubMed] [Google Scholar]
  97. Ukena D., Harnest U., Sakalauskas R., Magyar P., Vetter N., Steffen H., Leichtl S., Rathgeb F., Keller A., Steinijans V. W. Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur Respir J. 1997 Dec;10(12):2754–2760. doi: 10.1183/09031936.97.10122754. [DOI] [PubMed] [Google Scholar]
  98. Ulrik C. S., Lange P. Cigarette smoking and asthma. Monaldi Arch Chest Dis. 2001 Aug;56(4):349–353. [PubMed] [Google Scholar]
  99. Virchow J. C., Jr, Prasse A., Naya I., Summerton L., Harris A. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):578–585. doi: 10.1164/ajrccm.162.2.9905041. [DOI] [PubMed] [Google Scholar]
  100. Walters E. H., Walters J. Inhaled short acting beta2-agonist use in asthma: regular vs as needed treatment. Cochrane Database Syst Rev. 2000;(4):CD001285–CD001285. doi: 10.1002/14651858.CD001285. [DOI] [PubMed] [Google Scholar]
  101. Williamson I. J., Matusiewicz S. P., Brown P. H., Greening A. P., Crompton G. K. Frequency of voice problems and cough in patients using pressurized aerosol inhaled steroid preparations. Eur Respir J. 1995 Apr;8(4):590–592. [PubMed] [Google Scholar]
  102. Wilson A. J., Gibson P. G., Coughlan J. Long acting beta-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database Syst Rev. 2000;(2):CD001281–CD001281. doi: 10.1002/14651858.CD001281. [DOI] [PubMed] [Google Scholar]
  103. Wilson A. M., Dempsey O. J., Sims E. J., Lipworth B. J. Evaluation of salmeterol or montelukast as second-line therapy for asthma not controlled with inhaled corticosteroids. Chest. 2001 Apr;119(4):1021–1026. doi: 10.1378/chest.119.4.1021. [DOI] [PubMed] [Google Scholar]
  104. van Noord J. A., Smeets J. J., Raaijmakers J. A., Bommer A. M., Maesen F. P. Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action. Eur Respir J. 1996 Aug;9(8):1684–1688. doi: 10.1183/09031936.96.09081684. [DOI] [PubMed] [Google Scholar]

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