Skip to main content
SpringerLink
Log in
Book cover

Principles of Immunopharmacology pp 281–344Cite as

Drugs for the treatment of asthma and COPD

  • Chapter

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Selected readings

References

  1. Barnes PJ (2000) Mechanisms in COPD: differences from asthma. Chest 117: 10S–14S

    Article  PubMed  CAS  Google Scholar 

  2. Nelson HS (1995) Beta-adrenergic bronchodilators. N Engl J Med 333: 499–506

    PubMed  CAS  Google Scholar 

  3. Kips JC, Pauwels RA (2001) Long-acting inhaled β2-agonist therapy in asthma. Am J Respir Crit Care Med 164: 923–932

    PubMed  CAS  Google Scholar 

  4. Green SA, Spasoff AP, Coleman RA, Johnson M, Liggett SB (1996) Sustained activation of a G protein-coupled receptor via “anchored” agonist binding. Molecular localization of the salmeterol exosite within the 2-adrenergic receptor. J Biol Chem 271: 24029–2403

    PubMed  CAS  Google Scholar 

  5. Barnes PJ (1995) Beta-adrenergic receptors and their regulation. Am J Respir Crit Care Med 152: 838–860

    PubMed  CAS  Google Scholar 

  6. Kotlikoff MI, Kamm KE (1996) Molecular mechanisms of β-adrenergic relaxation of airway smooth muscle. Annu Rev Physiol 58: 115–141

    Article  PubMed  CAS  Google Scholar 

  7. Staples KJ, Bergmann M, Tomita K, Houslay MD, McPhee I, Barnes PJ, Giembycz MA, Newton R (2001) Adenosine 3′,5′-cyclic monophosphate (cAMP)-dependent inhibition of IL-5 from human T lymphocytes is not mediated by the cAMP-dependent protein kinase A. J Immunol 167: 2074–2080

    PubMed  CAS  Google Scholar 

  8. Barnes PJ (1999) Effect of beta agonists on inflammatory cells. J Allergy Clin Immunol 104: 10–17

    Google Scholar 

  9. Weston MC, Peachell PT (1998) Regulation of human mast cell and basophil function by cAMP. Gen Pharmacol 31: 715–719

    PubMed  CAS  Google Scholar 

  10. Howarth PH, Beckett P, Dahl R (2000) The effect of long-acting β2-agonists on airway inflammation in asthmatic patients. Respir Med 94(Suppl F): S22–S25

    PubMed  Google Scholar 

  11. Travers AH, Rowe BH, Barker S, Jones A, Camargo CA, Jr. (2002) The effectiveness of IV β-agonists in treating patients with acute asthma in the emergency department: a meta-analysis. Chest 122: 1200–1207

    Article  PubMed  CAS  Google Scholar 

  12. Crompton GK, Ayres JG, Basran G, Schiraldi G, Brusasco V, Eivindson A, Jamieson AH, Olsson H (1999) Comparison of oral bambuterol and inhaled salmeterol in patients with symptomatic asthma and using inhaled corticosteroids. Am J Respir Crit Care Med 159: 824–828

    PubMed  CAS  Google Scholar 

  13. Handley DA (2001) Single-isomer beta-agonists. Pharmacotherapy 21: 21S–27S

    PubMed  CAS  Google Scholar 

  14. Lotvall J, Palmqvist M, Arvidsson P, Maloney A, Ventresca GP, Ward J (2001) The therapeutic ratio of Ralbuterol is comparable with that of RS-albuterol in asthmatic patients. J Allergy Clin Immunol 108: 726–731

    Article  PubMed  CAS  Google Scholar 

  15. Walters EH, Walters JA, Gibson PW (2002) Regular treatment with long acting beta agonists versus daily regular treatment with short acting beta agonists in adults and children with stable asthma. Cochrane Database Syst Rev, CD003901

    Google Scholar 

  16. Nightingale JA, Rogers DF, Barnes PJ (2002) Comparison of the effects of salmeterol and formoterol in patients with severe asthma. Chest 121: 1401–1406

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Pauwels RA, Lofdahl CG, Postma DS, Tattersfield AE, O’Byrne P, Barnes PJ, Ullman A (1997) Effect of inhaled formoterol and budesonide on exacerbations of asthma. N Engl J Med 337: 1405–1411

    Article  PubMed  CAS  Google Scholar 

  19. O’Byrne PM, Barnes PJ, Rodriguez-Roisin R, Runnerstrom E, Sandstrom T, Svensson K, Tattersfield A (2001) Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am J Respir Crit Care Med 164: 1392–1397

    PubMed  CAS  Google Scholar 

  20. Appleton S, Smith B, Veale A, Bara A (2000) Long-acting β2-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2: CD001104: CD001104

    Google Scholar 

  21. Tattersfield AE, Lofdahl CG, Postma DS, Eivindson A, Schreurs AG, Rasidakis A, Ekstrom T (2001) Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial. Lancet 357: 257–261

    PubMed  CAS  Google Scholar 

  22. Nelson HS (2001) Advair: combination treatment with fluticasone propionate/salmeterol in the treatment of asthma. J Allergy Clin Immunol 107: 398–416

    PubMed  CAS  Google Scholar 

  23. Barnes PJ (2002) Scientific rationale for combination inhalers with a long-acting β2-agonists and corticosteroids. Eur Respir J 19: 182–191

    Article  PubMed  MathSciNet  CAS  Google Scholar 

  24. Nelson HS, Chapman KR, Pyke SD, Johnson M, Pritchard JN (2003) Enhanced synergy between fluticasone propionate and salmeterol inhaled from a single inhaler versus separate inhalers. J Allergy Clin Immunol 112: 29–36

    Article  PubMed  CAS  Google Scholar 

  25. Szafranski W, Ramirez A, Petersen S (2002) Budesonide/formoterol in a single inhaler provides sustained improvements in lung function in patients with moderate to severe COPD. Eur Resp J 20: 397S

    Google Scholar 

  26. Calverley P, Pauwels R, Vestbo J, Jones P, Pride N, Gulsvik A, Anderson J, Maden C; Trial of Inhaled Steroids and long-acting beta2 agonists study group (2003) Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomized controlled trial. Lancet 361: 449–456

    PubMed  CAS  Google Scholar 

  27. Grove A, Lipworth BJ (1995) Tolerance with β2-adrenoceptor agonists: time for reappraisal. Br J Clin Pharmacol 39: 109–118

    PubMed  CAS  Google Scholar 

  28. O’Connor BJ, Aikman SL, Barnes PJ (1992) Tolerance to the non-bronchodilator effects of inhaled β2-agonists. N Engl J Med 327: 1204–1208

    PubMed  CAS  Google Scholar 

  29. Cockcroft DW, McParland CP, Britto SA, Swystun VA, Rutherford BC (1993) Regular inhaled salbutamol and airway responsiveness to allergen. Lancet 342: 833–837

    Article  PubMed  CAS  Google Scholar 

  30. Hamid QA, Mak JC, Sheppard MN, Corrin B, Venter JC, Barnes PJ (1991) Localization of β2-adrenoceptor messenger RNA in human and rat lung using in situ hybridization: correlation with receptor autoradiography. Eur J Pharmacol 206: 133–138

    PubMed  CAS  Google Scholar 

  31. McGraw DW, Liggett SB (1997) Heterogeneity in betaadrenergic receptor kinase expression in the lung accounts for cell-specific desensitization of the beta2-adrenergic receptor. J Biol Chem 272: 7338–7344

    PubMed  CAS  Google Scholar 

  32. Yates DH, Sussman H, Shaw MJ, Barnes PJ, Chung KF (1995) Regular formoterol treatment in mild asthma: effect on bronchial responsiveness during and after treatment. Am J Resp Crit Care Med 152: 1170–1174

    PubMed  CAS  Google Scholar 

  33. Mak JCW, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ (1995) Protective effects of a glucocorticoid on down-regulation of pulmonary β2-adrenergic receptors in vivo. J Clin Invest 96: 99–106

    PubMed  CAS  Google Scholar 

  34. Yates DH, Kharitonov SA, Barnes PJ (1996) An inhaled glucocorticoid does not prevent tolerance to salmeterol in mild asthma. Am J Respir Crit Care Med 154: 1603–1607

    PubMed  CAS  Google Scholar 

  35. Kalra S, Swystun VA, Bhagat R, Cockcroft DW (1996) Inhaled corticosteroids do not prevevt the development of subsensitivity to salbutamol after twice daily salmeterol. Chest 109: 953–956

    PubMed  CAS  Google Scholar 

  36. Beasley R, Pearce N, Crane J, Burgess C (1999) Beta-agonists: what is the evidence that their use increases the risk of asthma morbidity and mortality? J Allergy Clin Immunol 104: S18–S30

    Article  PubMed  CAS  Google Scholar 

  37. Spitzer WO, Suissa S, Ernst P, Horwitz RI, Habbick B, Cockcroft D, Boivin JF, McNutt M, Buist AS, Rebuck AS (1992) The use of β-agonists and the rate of death and near-death from asthma. N Engl J Med 326: 501–506

    PubMed  CAS  Google Scholar 

  38. Suissa S, Ernst P, Benayoun S, Baltzan M, Cai B (2000) Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 343: 332–336

    Article  PubMed  CAS  Google Scholar 

  39. Sears MR, Taylor DR, Print CG, Lake DC, Li QQ, Flannery EM, Yates DM, Lucas MK, Herbison GP (1990) Regular inhaled beta-agonist treatment in bronchial asthma. Lancet 336: 1391–1396

    Article  PubMed  CAS  Google Scholar 

  40. Drazen JM, Israel E, Boushey HA, Chinchilli VM, Fahy JV, Fish JE, Lazarus SC, Lemanske RF, Martin RJ, Peters SP et al (1996) Comparison of regularly scheduled with as needed use of albuterol in mild asthma. N Engl J Med 335: 841–847

    Article  PubMed  CAS  Google Scholar 

  41. Dennis SM, Sharp SJ, Vickers MR, Frost CD, Crompton GK, Barnes PJ, Lee TH (2000) Regular inhaled salbutamol and asthma control: the TRUST randomised trial. Lancet 355: 1675–1679

    Article  PubMed  CAS  Google Scholar 

  42. Gauvreau GM, Jordana M, Watson RM, Cockroft DW, O’Byrne PM (1997) Effect of regular inhaled albuterol on allergen-induced late responses and sputum eosinophils in asthmatic subjects. Am J Respir Crit Care Med 156: 1738–1745

    PubMed  CAS  Google Scholar 

  43. Mcivor RA, Pizzichini E, Turner MO, Hussack P, Hargreave FE, Sears MR (1998) Potential masking effects of salmeterol on airway inflammation in asthma. Am J Respir Crit Care Med 158: 924–930

    PubMed  CAS  Google Scholar 

  44. Adcock IM, Stevens DA, Barnes PJ (1996) Interactions between steroids and β2-agonists. Eur Respir J 9: 160–168

    Article  PubMed  CAS  Google Scholar 

  45. McGraw DW, Almoosa KF, Paul RJ, Kobilka BK, Liggett SB (2003) Antithetic regulation by ?-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway β-agonist paradox. J Clin Invest 112: 619–626

    Article  PubMed  CAS  Google Scholar 

  46. Liggett SB (2002) Polymorphisms of the beta2-adrenergic receptor. N Engl J Med 346: 536–538

    Article  PubMed  CAS  Google Scholar 

  47. Peters MJ, Adcock IM, Brown CR, Barnes PJ (1995) β-Adrenoceptor agonists interfere with glucocorticoid receptor DNA binding in rat lung. Eur J Pharmacol (Molec Pharmacol Section) 289: 275–281

    PubMed  CAS  Google Scholar 

  48. Weinberger M, Hendeles L (1996) Theophylline in asthma. N Engl J Med 334: 1380–1388

    PubMed  CAS  Google Scholar 

  49. Barnes PJ (2003) Theophylline: new perspectives on an old drug. Am J Respir Crit Care Med 167: 813–818

    Article  PubMed  Google Scholar 

  50. Barnes PJ, Pauwels RA (1994) Theophylline in asthma: time for reappraisal? Eur Resp J 7: 579–591

    CAS  Google Scholar 

  51. Ward AJM, McKenniff M, Evans JM, Page CP, Costello JF (1993) Theophylline — an immunomodulatory role in asthma? Am Rev Respir Dis 147: 518–523

    PubMed  CAS  Google Scholar 

  52. Sullivan P, Bekir S, Jaffar Z, Page C, Jeffery P, Costello J (1994) Anti-inflammatory effects of low-dose oral theophylline in atopic asthma. Lancet 343: 1006–1008

    Article  PubMed  CAS  Google Scholar 

  53. Jaffar ZH, Sullivan P, Page C, Costello J (1996) Low-dose theophylline modulates T-lymphocyte activation in allergen-challenged asthmatics. Eur Respir J 9:456–462

    Article  PubMed  CAS  Google Scholar 

  54. Lim S, Tomita K, Caramori G, Jatakanon A, Oliver B, Keller A, Adcock I, Chung KF, Barnes PJ (2001) Low-dose theophylline reduces eosinophilic inflammation but not exhaled nitric oxide in mild asthma. Am J Respir Crit Care Med 164: 273–276

    PubMed  CAS  Google Scholar 

  55. Kidney J, Dominguez M, Taylor PM, Rose M, Chung KF, Barnes PJ (1995) Immunomodulation by theophylline in asthma: demonstration by withdrawal of therapy. Am J Resp Crit Care Med 151: 1907–1914

    PubMed  CAS  Google Scholar 

  56. Culpitt SV, de Matos C, Russell RE, Donnelly LE, Rogers DF, Barnes PJ (2002) Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in COPD. Am J Respir Crit Care Med 165: 1371–1376

    Article  PubMed  Google Scholar 

  57. Rabe KF, Magnussen H, Dent G (1995) Theophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants. Eur Respir J 8: 637–642

    PubMed  CAS  Google Scholar 

  58. Torphy TJ (1998) Phosphodiesterase isoenzymes. Am J Respir Crit Care Med 157: 351–370

    PubMed  CAS  Google Scholar 

  59. Feoktistov I, Biaggioni I (1997) Adenosine A2B receptors. Pharmacol Rev 49: 381–402

    PubMed  CAS  Google Scholar 

  60. Björk T, Gustafsson LE, Dahlén S-E (1992) Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine. Am Rev Respir Dis 145: 1087–1091

    Google Scholar 

  61. Barnes PJ (2001) IL-10: a key regulator of allergic disease. Clin Exp Allergy; 31: 667–669

    PubMed  CAS  Google Scholar 

  62. Mascali JJ, Cvietusa P, Negri J, Borish L (1996) Antiinflammatory effects of theophylline: modulation of cytokine production. Ann Allergy Asthma Immunol 77: 34–38

    PubMed  CAS  Google Scholar 

  63. Oliver B, Tomita K, Keller A, Caramori G, Adcock I, Chung KF, Barnes PJ, Lim S (2001) Low-dose theophylline does not exert its anti-inflammatory effects in mild asthma through upregulation of interleukin-10 in alveolar macrophages. Allergy 56: 1087–1090

    Article  PubMed  CAS  Google Scholar 

  64. Tomita K, Chikumi H, Tokuyasu H, Yajima H, Hitsuda Y, Matsumoto Y, Sasaki T (1999) Functional assay of NF-kappaB translocation into nuclei by laser scanning cytometry: inhibitory effect by dexamethasone or theophylline. Naunyn Schmiedebergs Arch Pharmacol 359: 249–255

    PubMed  CAS  Google Scholar 

  65. Ichiyama T, Hasegawa S, Matsubara T, Hayashi T, Furukawa S (2001) Theophylline inhibits NF-κB activation and IκBα degradation in human pulmonary epithelial cells. Naunyn Schmiedebergs Arch Pharmacol 364: 558–561

    Article  PubMed  CAS  Google Scholar 

  66. Yasui K, Hu B, Nakazawa T, Agematsu K, Komiyama A (1997) Theophylline accelerates human granulocyte apoptosis not via phosphodiesterase inhibition. J Clin Invest 100: 1677–1684

    PubMed  CAS  Google Scholar 

  67. Chung IY, Nam-Kung EK, Lee NM, Chang HS, Kim DJ, Kim YH, Park CS (2000) The downregulation of bcl-2 expression is necessary for theophylline-induced apoptosis of eosinophil. Cell Immunol 203: 95–102

    Article  PubMed  CAS  Google Scholar 

  68. Yasui K, Agematsu K, Shinozaki K, Hokibara S, Nagumo H, Nakazawa T, Komiyama A (2000) Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism. J Leukoc Biol 67: 529–535

    PubMed  CAS  Google Scholar 

  69. Ohta K, Yamashita N (1999) Apoptosis of eosinophils and lymphocytes in allergic inflammation. J Allergy Clin Immunol 104: 14–21

    PubMed  CAS  Google Scholar 

  70. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, Barnes PJ (2002) A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA 99: 8921–8926

    ADS  PubMed  CAS  Google Scholar 

  71. Zhang ZY, Kaminsky LS (1995) Characterization of human cytochromes P450 involved in theophylline 8-hydroxylation. Biochem Pharmacol; 50: 205–211

    PubMed  CAS  Google Scholar 

  72. Taylor DR, Ruffin D, Kinney CD, McDevitt DG (1983) Investigation of diurnal changes in the disposition of theophylline. Br J Clin Pharmac 16: 413–416

    CAS  Google Scholar 

  73. Parameswaran K, Belda J, Rowe BH (2000) Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma. Cochrane Database Syst Rev, CD002742

    Google Scholar 

  74. Rivington RN, Boulet LP, Cote J, Kreisman H, Small DI, Alexander M, Day A, Harsanyi Z, Darke AC (1995) Efficacy of Uniphyl, salbutamol, and their combination in asthmatic patients on high-dose inhaled steroids. Am J Respir Crit Care Med 151: 325–332

    PubMed  CAS  Google Scholar 

  75. Evans DJ, Taylor DA, Zetterstrom O, Chung KF, O’Connor BJ, Barnes PJ (1997) A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med 337: 1412–1418

    Article  PubMed  CAS  Google Scholar 

  76. Ukena D, Harnest U, Sakalauskas R, Magyar P, Vetter N, Steffen H, Leichtl S, Rathgeb F, Keller A, Steinijans VW (1997) Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur Respir J 10: 2754–2760

    Article  PubMed  CAS  Google Scholar 

  77. Lim S, Jatakanon A, Gordon D, Macdonald C, Chung KF, Barnes PJ (2000) 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 55: 837–841

    PubMed  CAS  Google Scholar 

  78. Wilson AJ, Gibson PG, Coughlan J (2000) Long acting beta-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database Syst Rev, CD001281

    Google Scholar 

  79. Shah L, Wilson AJ, Gibson PG, Coughlan J (2003) Long acting beta-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database Syst Rev, CD001281

    Google Scholar 

  80. Markham A, Faulds D (1998) Theophylline. A review of its potential steroid sparing effects in asthma. Drugs 56: 1081–1091

    PubMed  CAS  Google Scholar 

  81. Brenner MR, Berkowitz R, Marshall N, Strunk RC (1988) Need for theophylline in severe steroid-requiring asthmatics. Clin Allergy 18: 143–150

    PubMed  CAS  Google Scholar 

  82. Tinkelman DG, Reed CE, Nelson HS, Offord KP (1993) Aerosol beclomethasone diprionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. Pediatr 92: 64–77

    CAS  Google Scholar 

  83. Reed CE, Offord KP, Nelson HS, Li JT, Tinkelman DG (1998) Aerosol beclomethasone dipropionate spray compared with theophylline as primary treatment for chronic mild-to-moderate asthma. The American Academy of Allergy, Asthma and Immunology Beclomethasone Dipropionate-Theophylline Study Group. J Allergy Clin Immunol 101: 14–23

    Article  PubMed  CAS  Google Scholar 

  84. Dahl R, Larsen BB, Venge P (2002) Effect of long-term treatment with inhaled budesonide or theophylline on lung function, airway reactivity and asthma symptoms. Respir Med 96: 432–438

    PubMed  CAS  Google Scholar 

  85. Global Initiative for Asthma (2002) Global strategy for asthma management and prevention. NHLBI/WHO Workshop Report. NIH Publication 02-3659

    Google Scholar 

  86. Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS (2001) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 163: 1256–1276

    PubMed  CAS  Google Scholar 

  87. ZuWallack RL, Mahler DA, Reilly D, Church N, Emmett A, Rickard K, Knobil K (2001) Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest 119: 1661–1670

    Article  PubMed  CAS  Google Scholar 

  88. Kirsten DK, Wegner RE, Jorres RA, Magnussen H (1993) Effects of theophylline withdrawal in severe chronic obstructive pulmonary disease. Chest 104: 1101–1107

    PubMed  CAS  Google Scholar 

  89. Chrystyn H, Mulley BA, Peake MD (1988) Dose response relation to oral theophylline in severe chronic obstructive airway disease. Br Med J 297: 1506–1510

    CAS  Google Scholar 

  90. Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, Adcock IM (2002) Expression and activity of histone deacetylases (HDACs) in human asthmatic airways. Am J Respir Crit Care Med 166: 392–396

    Article  PubMed  Google Scholar 

  91. Wessler IK, Kirkpatrick CJ (2001) The non-neuronal cholinergic system: an emerging drug target in the airways. Pulm Pharmacol Ther 14: 423–434

    PubMed  CAS  Google Scholar 

  92. Tamaoki J, Chiyotani A, Tagaya E, Sakai N, Konno K (1994) Effect of long term treatment with oxitropium bromide on airway secretion in chronic bronchitis and diffuse panbronchiolitis. Thorax 49: 545–548

    PubMed  CAS  Google Scholar 

  93. Stoodley RG, Aaron SD, Dales RE (1999) The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a meta-analysis of randomized clinical trials. Ann Emerg Med 34: 8–18

    Article  PubMed  CAS  Google Scholar 

  94. Rennard SI, Serby CW, Ghafouri M, Johnson PA, Friedman M (1996) Extended therapy with ipratropium is associated with improved lung function in patients with COPD. A retrospective analysis of data from seven clinical trials. Chest 110: 62–70

    PubMed  CAS  Google Scholar 

  95. Frith PA, Jenner B, Dangerfield R, Atkinson J, Drennan C (1986) Oxitropium bromide. Dose response and time-response study of a new anticholinergic bronchodilator drug. Chest 89: 249–253

    PubMed  CAS  Google Scholar 

  96. Coe CI, Barnes PJ (1986) Reduction of nocturnal asthma by an inhaled anticholinergic drug. Chest 90: 485–488

    PubMed  CAS  Google Scholar 

  97. Combivent inhlation study group (1997) Routine nebulized ipratropium and albuterol together are better than either alone in COPD. Chest 112: 1514–1521

    Google Scholar 

  98. Hansel TT, Barnes PJ (2002) Tiotropium bromide: a novel once-daily anticholinergic bronchodilator for the treatment of COPD. Drugs Today 38: 585–600

    Article  CAS  PubMed  Google Scholar 

  99. Disse B, Speck GA, Rominger KL, Witek TJ, Hammer R (1999) Tiotropium (Spiriva): mechanistical considerations and clinical profile in obstructive lung disease. Life Sci 64: 457–464

    Article  PubMed  CAS  Google Scholar 

  100. Vincken W, van Noord JA, Greefhorst AP, Bantje TA, Kesten S, Korducki L, Cornelissen PJ; Dutch/Belgian Tiotropium Study Group (2002) Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J 19: 209–216

    Article  PubMed  CAS  Google Scholar 

  101. Casaburi R, Mahler DA, Jones PW, Wanner A, San PG, ZuWallack RL, Menjoge SS, Serby CW, Witek T Jr (2002) A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J 19: 217–224

    Article  PubMed  CAS  Google Scholar 

  102. Newcomb R, Tashkin DP, Hui KK, Connolly ME, Lee E, Dauphinee B (1985) Rebound hyperresponsiveness to muscarinic stimulation after chronic therapy with an inhaled muscarinic antagonist. Am Rev Respir Dis 132: 12–15

    PubMed  CAS  Google Scholar 

  103. Patel HJ, Barnes PJ, Takahashi T, Tadjkarimi S, Yacoub MH, Belvisi MG (1995) Characterization of prejunctional muscarinic autoreceptors in human and guinea-pig trachea in vitro. Am J Resp Crit Care Med 152: 872–878

    PubMed  CAS  Google Scholar 

  104. Alabaster VA (1997) Discovery and development of selective M3 antagonists for clinical use. Life Sci 60: 1053–1060

    Article  PubMed  CAS  Google Scholar 

  105. Schelfhout VJ, Joos GF, Ferrer P, Luria X, Pauwels RA (2003) Activity of LAS 34273, a new long-acting anticholinergic antagonist. Am J Resp Crit Care Med 167: A93

    Google Scholar 

  106. Tennant RC, Erin EM, Barnes PJ, Hansel TT (2003) Long-acting α2-adrenoceptor agonists or tiotropium bromide for patients with COPD: is combination therapy justified? Curr Opin Pharmacol 3: 270–276

    PubMed  CAS  Google Scholar 

  107. Rowe BH, Bretzlaff JA, Bourdon C, Bota GW, Camargo CA, Jr. (2000) Intravenous magnesium sulfate treatment for acute asthma in the emergency department: a systematic review of the literature. Ann Emerg Med 36: 181–190

    PubMed  CAS  Google Scholar 

  108. Silverman RA, Osborn H, Runge J, Gallagher EJ, Chiang W, Feldman J, Gaeta T, Freeman K, Levin B, Mancherje N et al; Acute Asthma/Magnesium Study Group (2002) IV magnesium sulfate in the treatment of acute severe asthma: a multicenter randomized controlled trial. Chest 122: 489–497

    Article  PubMed  CAS  Google Scholar 

  109. Emelyanov A, Fedoseev G, Barnes PJ (1999) Reduced intracellular magnesium concentrations in asthmatic subjects. Eur Respir J 13: 38–40

    Article  PubMed  CAS  Google Scholar 

  110. Hughes R, Goldkorn A, Masoli M, Weatherall M, Burgess C, Beasley R (2003) Use of isotonic nebulised magnesium sulphate as an adjuvant to salbutamol in treatment of severe asthma in adults: randomised placebocontrolled trial. Lancet 361: 2114–2117

    Article  PubMed  CAS  Google Scholar 

  111. Black JL, Armour CL, Johnson PRA, Alouan LA, Barnes PJ (1990) The action of a potassium channel activator BRL 38227 (lemakalim) on human airway smooth muscle. Am Rev Respir Dis 142: 1384–1389

    PubMed  CAS  Google Scholar 

  112. Pelaia G, Gallelli L, Vatrella A, Grembiale RD, Maselli R, De Sarro GB, Marsico SA (2002) Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary disease. Life Sci 70: 977–990

    Article  PubMed  CAS  Google Scholar 

  113. Kidney JC, Fuller RW, Worsdell Y-M, Lavender EA, Chung KF, Barnes PJ (1993) Effect of an oral potassium channel activator BRL 38227 on airway function and responsiveness in asthmatic patients: comparison with oral salbutamol. Thorax 48: 130–134

    PubMed  CAS  Google Scholar 

  114. Ramnarine SI, Liu YC, Rogers DF (1998) Neuroregulation of mucus secretion by opioid receptors and K(ATP) and BK(Ca) channels in ferret trachea in vitro. Br J Pharmacol 123: 1631–1638

    Article  PubMed  CAS  Google Scholar 

  115. Fox AJ, Barnes PJ, Venkatesan P, Belvisi MG (1997) Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves. J Clin Invest 99: 513–519

    PubMed  CAS  Google Scholar 

  116. Angus RM, Mecallaum MJA, Hulks G, Thomson NC (1993) Bronchodilator, cardiovascular and cyclic guanylyl monophosphate response to high dose infused atrial natriuretic peptide in asthma. Am Rev Respir Dis 147: 1122–1125

    PubMed  CAS  Google Scholar 

  117. Fluge T, Forssmann WG, Kunkel G, Schneider B, Mentz P, Forssmann K, Barnes PJ, Meyer M (1999) Bronchodilation using combined urodilatin — albuterol administration in asthma: a randomized, double-blind, placebo-controlled trial. Eur J Med Res 4: 411–415

    PubMed  CAS  Google Scholar 

  118. Linden A, Hansson L, Andersson A, Palmqvist M, Arvidsson P, Lofdahl CG, Larsson P, Lotvall J (2003) Bronchodilation by an inhaled VPAC(2) receptor agonist in patients with stable asthma. Thorax 58: 217–221

    Article  PubMed  CAS  Google Scholar 

  119. Barnes PJ (1995) Inhaled glucocorticoids for asthma. N Engl J Med 332: 868–875

    Article  PubMed  CAS  Google Scholar 

  120. Barnes PJ (1998) Antiinflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci 94: 557–572

    PubMed  CAS  Google Scholar 

  121. Barnes PJ, Adcock IM (2003) How do corticosteroids work in asthma? Ann Intern Med 139: 359–370

    PubMed  CAS  Google Scholar 

  122. Juniper EF, Kline PA, Yan Zieleshem MA, Ramsdale EH, O’Byrne PM, Hargreave FE (1990) Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics. Eur Respir J 3: 1122–1127

    PubMed  CAS  Google Scholar 

  123. Mak JCW, Nishikawa M, Barnes PJ (1995) Glucocorticosteroids increase β2-adrenergic receptor transcription in human lung. Am J Physiol 12: L41–L46

    Google Scholar 

  124. Baraniuk JN, Ali M, Brody D, Maniscalco J, Gaumond E, Fitzgerald T, Wong G, Yuta A, Mak JC, Barnes PJ et al (1997) Glucocorticoids induce β2-adrenergic receptor function in human nasal mucosa. Am J Respir Crit Care Med 155: 704–710

    PubMed  CAS  Google Scholar 

  125. Chong LK, Drury DE, Dummer JF, Ghahramani P, Schleimer RP, Peachell PT (1997) Protection by dexamethasone of the functional desensitization to β2-adrenoceptor-mediated responses in human lung mast cells. Br J Pharmacol 121: 717–722

    PubMed  CAS  Google Scholar 

  126. Gambertoglio JG, Amend WJC, Benet LZ (1980) Pharmacokinetics and bioavailability of prednisone and prednisolone in healthy volunteers and patients: a review. J Pharmacokin Biopharm 8: 1–52

    Article  CAS  Google Scholar 

  127. Barnes PJ, Greening AP, Crompton GK (1995) Gluco-corticoid resistance in asthma. Am J Respir Crit Care Med 152: 125S–140S

    Google Scholar 

  128. Barnes PJ, Pedersen S, Busse WW (1998) Efficacy and safety of inhaled corticosteroids: an update. Am J Respir Crit Care Med 157: S1–S53

    PubMed  CAS  Google Scholar 

  129. Markham A, Bryson HM (1995) Deflazacort. A review of its pharmacological properties and therapeutic efficacy. Drugs 50: 317–333

    PubMed  CAS  Google Scholar 

  130. Harrison BDN, Stokes TC, Hart GJ, Vaughan DA, Ali NJ, Robinson AA (1986) Need for intravenous hydrocortisone in addition to oral prednisolone in patients admitted to hospital with severe asthma without ventilatory failure. Lancet 1: 181–184

    PubMed  CAS  Google Scholar 

  131. Malo JL, Cartier A, Merland N, Ghezzo H, Burek A, Morris J, Jennings BH (1989) Four-times-a-day dosing frequency is better than twice-a-day regimen in subjects requiring a high-dose inhaled steroid, budesonide, to control moderate to severe asthma. Am Rev Respir Dis 140: 624–628

    PubMed  CAS  Google Scholar 

  132. Metzger WJ, Hampel FC Jr, Sugar M (2002) Once-daily budesonide inhalation powder (Pulmicort Turbuhaler) is effective and safe in adults previously treated with inhaled corticosteroids. J Asthma 39: 65–75

    PubMed  CAS  Google Scholar 

  133. Szefler SJ, Eigen H (2002) Budesonide inhalation suspension: a nebulized corticosteroid for persistent asthma. J Allergy Clin Immunol 109: 730–742

    PubMed  Google Scholar 

  134. Edmonds ML, Camargo CA, Jr.., Pollack CV, Jr., Rowe BH (2003) Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev, CD002308

    Google Scholar 

  135. Pauwels RA, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, Ullman A, Lamm CJ, O’Byrne PM; START Investigators Group (2003) Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 361: 1071–1076

    Article  PubMed  CAS  Google Scholar 

  136. Adams N, Bestall J, Jones P (2001) Inhaled beclomethasone at different doses for long-term asthma. Cochrane Database Syst Rev, CD002879

    Google Scholar 

  137. Adams N, Bestall J, Jones PW (2001) Budesonide at different doses for chronic asthma (Cochrane Review). Cochrane Database Syst Rev 4: CD003271

    Google Scholar 

  138. Adams N, Bestall JM, Jones PW (2002) Inhaled fluticasone at different doses for chronic asthma. Cochrane Database Syst Rev, CD003534

    Google Scholar 

  139. Hawkins G, McMahon AD, Twaddle S, Wood SF, Ford I, Thomson NC (2003) Stepping down inhaled corticosteroids in asthma: randomised controlled trial. Br Med J 326: 1115

    Google Scholar 

  140. Barnes PJ, Ito K, Adcock IM (2004) A mechanism of corticosteroid resistance in COPD: inactivation of histone deacetylase. Lancet 363: 731–733

    PubMed  CAS  Google Scholar 

  141. Alsaeedi A, Sin DD, McAlister FA (2002) The effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review of randomized placebo-controlled trials. Am J Med 113: 59–65

    Article  PubMed  CAS  Google Scholar 

  142. Davies L, Angus RM, Calverley PM (1999) Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet 354: 456–460

    PubMed  CAS  Google Scholar 

  143. Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, Light RW, Anderson P, Morgan NA (1999) Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med 340: 1941–1947

    Article  PubMed  CAS  Google Scholar 

  144. Lipworth BJ (1999) Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Intern Med 159: 941–955

    Article  PubMed  CAS  Google Scholar 

  145. Pedersen S (2001) Do inhaled corticosteroids inhibit growth in children? Am J Respir Crit Care Med 164: 521–535

    PubMed  CAS  Google Scholar 

  146. Agertoft L, Pedersen S (2000) Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med 343: 1064–1069

    Article  PubMed  CAS  Google Scholar 

  147. Cumming RG, Mitchell P, Leeder SR (1997) Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 337: 8–14

    Article  PubMed  CAS  Google Scholar 

  148. Garbe E, LeLorier J, Boivin J-F, Suissa S (1997) Inhaled and nasal glucocorticoids and the risks of ocular hypertension or open-angel glaucoma. JAMA 227: 722–727

    Google Scholar 

  149. Williamson IJ, Matusiewicz SP, Brown PH, Greening AP, Crompton GK (1995) Frequency of voice problems and cough in patients using pressurised aerosol inhaled steroid preparations. Eur Resp J 8: 590–592

    CAS  Google Scholar 

  150. Harrison TW, Wisniewski A, Honour J, Tattersfield AE (2001) Comparison of the systemic effects of fluticasone propionate and budesonide given by dry powder inhaler in healthy and asthmatic subjects. Thorax 56:186–191

    Article  PubMed  CAS  Google Scholar 

  151. Brutsche MH, Brutsche IC, Munawar M, Langley SJ, Masterson CM, Daley-Yates PT, Brown R, Custovic A, Woodcock A (2000) Comparison of pharmacokinetics and systemic effects of inhaled fluticasone propionate in patients with asthma and healthy volunteers: a randomised crossover study. Lancet 356: 556–561

    Article  PubMed  CAS  Google Scholar 

  152. Martin RJ (2002) Therapeutic significance of distal airway inflammation in asthma. J Allergy Clin Immunol 109: S447–S460

    Article  PubMed  Google Scholar 

  153. Leach CL, Davidson PJ, Boudreau RJ (1998) Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFCbeclomethasone. Eur Respir J 12: 1346–1353

    Article  PubMed  CAS  Google Scholar 

  154. Hauber HP, Gotfried M, Newman K, Danda R, Servi RJ, Christodoulopoulos P, Hamid Q (2003) Effect of HFAflunisolide on peripheral lung inflammation in asthma. J Allergy Clin Immunol 112: 58–63

    Article  PubMed  CAS  Google Scholar 

  155. Martin RJ, Szefler SJ, Chinchilli VM, Kraft M, Dolovich M, Boushey HA, Cherniack RM, Craig TJ, Drazen JM, Fagan JK et al (2002) Systemic effect comparisons of six inhaled corticosteroid preparations. Am J Respir Crit Care Med 165: 1377–1383

    Article  PubMed  Google Scholar 

  156. Haahtela T, Jarvinen M, Kava T, Kiviranta K, Koskinen S, Lehtonen K, Nikander K, Persson T, Selroos O, Sovijarvi A et al (1994) Effects of reducing or discontinuing inhaled budesonide in patients with mild asthma. N Engl J Med 331: 700–705

    Article  PubMed  CAS  Google Scholar 

  157. Agertoft L, Pedersen S (1994) Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Resp Med 5: 369–372

    Google Scholar 

  158. Selroos O, Pietinalcho A, Lofroos A-B, Riska A (1995) Effect of early and late intervention with inhaled corticosteroids in asthma. Chest 108: 1228–1234

    PubMed  CAS  Google Scholar 

  159. Dent G (2002) Ciclesonide. Curr Opin Investig Drugs 3: 78–83

    PubMed  CAS  Google Scholar 

  160. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, Gronemeyer H, Resche-Rigon M (1997) Synthetic glucocorticoids that dissociate transactivation and AP-1_transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol 11:1245–1255

    Article  PubMed  CAS  Google Scholar 

  161. Belvisi MG, Brown TJ, Wicks S, Foster ML (2001) New Glucocorticosteroids with an improved therapeutic ratio? Pulm Pharmacol Ther 14: 221–227

    PubMed  CAS  Google Scholar 

  162. Schacke H, Docke WD, Asadullah K (2002) Mechanisms involved in the side-effects of glucocorticoids. Pharmacol Ther 96: 23–43

    Article  PubMed  CAS  Google Scholar 

  163. Manolitsas ND, Wang J, Devalia J, Trigg CJ, McAuley AE, Davies RJ (1995) Regular albuterol, nedocromil sodium and bronchial inflammation in asthma. Am J Respir Crit Care Med 152: 1925–1930

    Google Scholar 

  164. Norris AA (1996) Pharmacology of sodium cromoglycate. Clin Exp Allergy 26(Suppl 4): 5–7

    PubMed  MathSciNet  CAS  Google Scholar 

  165. Thomson NC (1989) Nedocromil sodium: an overview. Resp Med 83: 269–276

    ADS  CAS  Google Scholar 

  166. Tasche MJ, Uijen JH, Bernsen RM, de Jongste JC, van Der W (2000) Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review. Thorax 55: 913–920

    Article  PubMed  CAS  Google Scholar 

  167. Wouden JC, Tasche MJ, Bernsen RM, Uijen JH, Jongste JC, Ducharme FM (2003) Inhaled sodium cromoglycate for asthma in children. Cochrane Database Syst Rev, CD002173

    Google Scholar 

  168. van Ganse E, Kaufman L, Derde MP, Yernault JC, Delaunois L (1997) Effects of antihistamines in adult asthma: a meta-analysis of clinical trials. Eur Respir J 10: 2216–2224

    PubMed  Google Scholar 

  169. Lordan JL, Holgate ST (2002) H1-antihistamines in asthma. Clin Allergy Immunol 17: 221–248

    PubMed  CAS  Google Scholar 

  170. Grant SM, Goa KL, Fitton A, Sorkin EM (1990) Ketotifen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma and allergic disorders. Drugs 40: 412–448

    PubMed  CAS  Google Scholar 

  171. Canny GJ, Reisman J, Levison H (1997) Does ketotifen have a steroid-sparing effect in childhood asthma? Eur Respir J 10: 65–70

    Article  PubMed  CAS  Google Scholar 

  172. Bustos GJ, Bustos D, Romero O (1995) Prevention of asthma with ketotifen in preasthmatic children: a three-year follow-up study. Clin Exp Allergy 25: 568–573

    PubMed  CAS  Google Scholar 

  173. Leff AR (2001) Regulation of leukotrienes in the management of asthma: biology and clinical therapy. Annu Rev Med 52: 1–14

    PubMed  CAS  Google Scholar 

  174. Szczeklik A, Stevenson DD (2003) Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol 111: 913–921

    Article  PubMed  CAS  Google Scholar 

  175. Calhoun WJ (2001) Anti-leukotrienes for asthma. Curr Opin Pharmacol 1: 230–234

    PubMed  CAS  Google Scholar 

  176. Ducharme FM (2003) Inhaled glucocorticoids versus leukotriene receptor antagonists as single agent asthma treatment: systematic review of current evidence. Br Med J 326: 621–624

    CAS  Google Scholar 

  177. Ducharme F (2002) Anti-leukotrienes as add-on therapy to inhlaed glucocorticoids in patients with asthma: systematic review of current evidence. Br Med J 324:1545–1548

    CAS  Google Scholar 

  178. Nelson HS, Busse WW, Kerwin E, Church N, Emmett A, Rickard K, Knobil K (2000) Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast. J Allergy Clin Immunol 106: 1088–1095

    PubMed  CAS  Google Scholar 

  179. Ringdal N, Eliraz A, Pruzinec R, Weber HH, Mulder PG, Akveld M, Bateman ED; International Study Group (2003) The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. Respir Med 97: 234–241

    PubMed  CAS  Google Scholar 

  180. Robinson DS, Campbell DA, Barnes PJ (2001) Addition of an anti-leukotriene to therapy in chronic severe asthma in a clinic setting: a double-blind, randomised, placebo-controlled study. Lancet 357: 2007–2011

    Article  PubMed  CAS  Google Scholar 

  181. Dahlen SE, Malmstrom K, Nizankowska E, Dahlen B, Kuna P, Kowalski M, Lumry WR, Picado C, Stevenson DD, Bousquet J et al (2002) Improvement of aspirinintolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial. Am J Respir Crit Care Med 165: 9–14

    PubMed  Google Scholar 

  182. Coreno A, Skowronski M, Kotaru C, McFadden ER, Jr. (2000) Comparative effects of long-acting beta2-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma. J Allergy Clin Immunol 106: 500–506

    Article  PubMed  CAS  Google Scholar 

  183. Nathan RA (2003) Pharmacotherapy for allergic rhinitis: a critical review of leukotriene receptor antagonists compared with other treatments. Ann Allergy Asthma Immunol 90: 182–190

    PubMed  CAS  Google Scholar 

  184. Diamant Z, Hiltermann JT, van Rensen EL, Callenbach PM, Veselic-Charvat M, van der Veen H, Sont JK, Sterk PJ (1997) Te effect of inhaled leukotriene D4 and methacholine on sputum cell differentials in asthma. Am J Respir Crit Care Med 155: 1247–1253

    PubMed  CAS  Google Scholar 

  185. Minoguchi K, Kohno Y, Minoguchi H, Kihara N, Sano Y, Yasuhara H, Adachi M (2002) Reduction of eosinophilic inflammation in the airways of patients with asthma using montelukast. Chest 121: 732–738

    Article  PubMed  CAS  Google Scholar 

  186. O’Sullivan S, Akveld M, Burke CM, Poulter LW (2003) Effect of the addition of montelukast to inhaled fluticasone propionate on airway inflammation. Am J Respir Crit Care Med 167: 745–750

    PubMed  Google Scholar 

  187. Montuschi P, Kharitonov SA, Ciabattoni G, Barnes PJ (2003) Exhaled leukotrienes and prostaglandins in COPD. Thorax 58: 585–588

    Article  PubMed  CAS  Google Scholar 

  188. Gompertz S, Stockley RA (2002) A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD. Chest 122: 289–294

    Article  PubMed  CAS  Google Scholar 

  189. Keogh KA, Specks U (2003) Churg-Strauss syndrome. clinical presentation, antineutrophil cytoplasmic antibodies, and leukotriene receptor antagonists. Am J Med 115: 284–290

    Article  PubMed  CAS  Google Scholar 

  190. Lilly CM, Churg A, Lazarovich M, Pauwels R, Hendeles L, Rosenwasser LJ, Ledford D, Wechsler ME (2002) Asthma therapies and Churg-Strauss syndrome. J Allergy Clin Immunol 109: S1–19

    Article  PubMed  Google Scholar 

  191. Barnes PJ (2003) Anti-leukotrienes: here to stay? Curr Opin Pharmacol 3: 257–263

    PubMed  CAS  Google Scholar 

  192. Palmer LJ, Silverman ES, Weiss ST, Drazen JM (2002) Pharmacogenetics of asthma. Am J Respir Crit Care Med 165: 861–866

    Article  PubMed  Google Scholar 

  193. Back M (2002) Functional characteristics of cysteinylleukotriene receptor subtypes. Life Sci 71: 611–622

    PubMed  CAS  Google Scholar 

  194. Hill SJ, Tattersfield AE (1995) Corticosteroid sparing agents in asthma. Thorax 50: 577–582

    PubMed  CAS  Google Scholar 

  195. Shiner RJ, Nunn AJ, Chung KF, Geddes DM (1990) Randomized, double-blind, placebo-controlled trial of methotrexate in steroid-dependent asthma. Lancet 336: 137–140

    Article  PubMed  CAS  Google Scholar 

  196. Davies H, Olson L, Gibson P (2000) Methotrexate as a steroid sparing agent for asthma in adults. Cochrane Database Syst Rev 2: CD000391: CD000391

    Google Scholar 

  197. Nierop G, Gijzel WP, Bel EH, Zwinderman AH, Dijkman JH (1992) Auranofin in the treatment of steroid dependent asthma: a double blind study. Thorax 47:349–354

    PubMed  CAS  Google Scholar 

  198. Evans DJ, Cullinan P, Geddes DM (2001) Gold as an oral corticosteroid sparing agent in stable asthma. Cochrane Database Syst Rev, CD002985

    Google Scholar 

  199. Lock SH, Kay AB, Barnes NC (1996) Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma. Am J Respir Crit Care Med 153: 509–514

    PubMed  CAS  Google Scholar 

  200. Evans DJ, Cullinan P, Geddes DM (2001) Cyclosporin as an oral corticosteroid sparing agent in stable asthma (Cochrane Review). Cochrane Database Syst Rev 2:CD002993

    Google Scholar 

  201. Salmun LM, Barlan I, Wolf HM, Eibl M, Twarog FJ, Geha RS, Schneider LC (1999) Effect of intravenous immunoglobulin on steroid consumption in patients with severe asthma: a double-blind, placebo-controlled, randomized trial. J Allergy Clin Immunol 103: 810–815

    Article  PubMed  CAS  Google Scholar 

  202. Niggemann B, Leupold W, Schuster A, Schuster R, v Berg A, Grubl A, v d Hardt H, Eibl MM, Wahn U (1998) Prospective, double-blind, placebo-controlled, multicentre study on the effect of high-dose, intravenous immunoglobulin in children and adolescents with severe bronchial asthma. Clin Exp Allergy 28: 205–210

    Article  PubMed  CAS  Google Scholar 

  203. Sigman K, Ghibu F, Sommerville W, Toledano BJ, Bastein Y, Cameron L, Hamid QA, Mazer B (1998) Intravenous immunoglobulin inhibits IgE production in human B lymphocytes. J Allergy Clin Immunol 102: 421–427

    Article  PubMed  CAS  Google Scholar 

  204. Barnes PJ (1996) Is there a role for immunotherapy in the treatment of asthma? No. Am J Respir Crit Care Med 154: 1227–1228

    PubMed  CAS  Google Scholar 

  205. Creticos PS, Reed CE, Norman PS, Khoury J, Adkinson NF, Jr., Buncher CR, Busse WW, Bush RK, Gadde J, Li JT et al (1996) Ragweed immunotherapy in adult asthma. N Engl J Med 334: 501–506

    Article  PubMed  CAS  Google Scholar 

  206. Adkinson NF, Jr., Eggleston PA, Eney D, Goldstein EO, Schuberth KC, Bacon JR, Hamilton RG, Weiss ME, Arshad H, Meinert CL et al (1997) A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med 336: 324–331

    Article  PubMed  CAS  Google Scholar 

  207. Abramson MJ, Puy RM, Weiner JM (2000) Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2: CD001186: CD001186

    Google Scholar 

  208. Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K (1998) Role of interleukin 10 in specific immunotherapy. J Clin Invest 102: 98–106

    PubMed  CAS  Google Scholar 

  209. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA (2003) IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33: 1205–1214

    Article  PubMed  CAS  Google Scholar 

  210. Haselden BM, Kay AB, Larche M (2000) Peptide-mediated immune responses in specific immunotherapy. Int Arch Allergy Immunol 122: 229–237

    Article  PubMed  CAS  Google Scholar 

  211. Oldfield WL, Larche M, Kay AB (2002) Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet 360: 47–53

    Article  PubMed  CAS  Google Scholar 

  212. Fahy JV (2000) Reducing IgE levels as a strategy for the treatment of asthma. Clin Exp Allergy 30(Suppl 1): 16–21

    PubMed  Google Scholar 

  213. Barnes PJ (2000) Anti-IgE therapy in asthma: rationale and therapeutic potential. Int Arch Allergy Immunol 123: 196–204

    Article  PubMed  CAS  Google Scholar 

  214. Milgrom H, Fick RB Jr, Su JQ, Reimann JD, Bush RK, Watrous ML, Metzger WJ (1999) Treatment of allergic asthma with monoclonal anti-IgE antibody. N Engl J Med 341: 1966–1973

    Article  PubMed  CAS  Google Scholar 

  215. Soler M, Matz J, Townley R, Buhl R, O’Brien J, Fox H, Thirlwell J, Gupta N, Della Cioppa G (2001) The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 18: 254–261

    PubMed  CAS  Google Scholar 

  216. Corren J, Casale T, Deniz Y, Ashby M (2003) Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol 111: 87–90

    Article  PubMed  CAS  Google Scholar 

  217. Chervinsky P, Casale T, Townley R, Tripathy I, Hedgecock S, Fowler-Taylor A, Shen H, Fox H (2003) Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol 91: 160–167

    PubMed  CAS  Google Scholar 

  218. Walker S, Monteil M, Phelan K, Lasserson TJ, Walters EH (2003) Anti-IgE for chronic asthma. Cochrane Database Syst Rev, CD003559

    Google Scholar 

  219. Barnes PJ (2000) New treatments for asthma. Eur J Int Med 11: 9–20

    MATH  MathSciNet  CAS  Google Scholar 

  220. Barnes PJ (1999) Therapeutic strategies for allergic diseases. Nature 402: B31–B38

    Article  ADS  PubMed  CAS  Google Scholar 

  221. Barnes PJ (2002) New treatments for COPD. Nature Rev Drug Disc 1: 437–445

    CAS  Google Scholar 

  222. Barnes PJ (2003) New treatments for COPD. Thorax 58: 803–808

    Article  PubMed  CAS  Google Scholar 

  223. Cochrane GM, Horne R, Chanez P (1999) Compliance in asthma. Respir Med 93: 763–769

    PubMed  CAS  Google Scholar 

  224. Barnes PJ (2003) New concepts in COPD. Ann Rev Med 54: 113–129

    Article  PubMed  CAS  Google Scholar 

  225. Roses AD (2000) Pharmacogenetics and future drug development and delivery. Lancet 355: 1358–1361

    Article  PubMed  CAS  Google Scholar 

  226. Barnes PJ, Chung KF, Page CP (1998) Inflammatory mediators of asthma: an update. Pharmacol Rev 50: 515–596

    PubMed  CAS  Google Scholar 

  227. Beeh KM, Kornmann O, Buhl R, Culpitt SV, Giembycz MA, Barnes PJ (2003) Neutrophil chemotactic activity of sputum from patients with COPD: role of interleukin 8 and leukotriene B4. Chest 123: 1240–1247

    PubMed  CAS  Google Scholar 

  228. Goldie RG, Henry PJ (1999) Endothelins and asthma. Life Sci 65: 1–15

    Article  PubMed  CAS  Google Scholar 

  229. Benigni A, Remuzzi G (1999) Endothelin antagonists. Lancet 353: 133–138

    Article  PubMed  CAS  Google Scholar 

  230. Macnee W (2001) Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol 429: 195–207

    Article  PubMed  CAS  Google Scholar 

  231. Cuzzocrea S, Riley DP, Caputi AP, Salvemini D (2001) Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev 53: 135–159

    PubMed  CAS  Google Scholar 

  232. Hobbs AJ, Higgs A, Moncada S (1999) Inhibition of nitric oxide synthase as a potential therapeutic target. Annu Rev Pharmacol Toxicol 39: 191–220

    Article  PubMed  CAS  Google Scholar 

  233. Hansel TT, Kharitonov SA, Donnelly LE, Erin EM, Currie MG, Moore WM, Manning PT, Recker DP, Barnes PJ (2003) A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics. FASEB J 17: 1298–1300

    PubMed  CAS  Google Scholar 

  234. Barnes PJ (2001) Cytokine modulators as novel therapies for airway disease. Eur Respir J 34(Suppl): 67s–77s

    MathSciNet  CAS  Google Scholar 

  235. Barnes PJ (2002) Cytokine modulators as novel therapies for asthma. Ann Rev Pharmacol Toxicol 42: 81–98

    CAS  Google Scholar 

  236. Barnes PJ, Lim S (1998) Inhibitory cytokines in asthma. Mol Medicine Today 4: 452–458

    CAS  Google Scholar 

  237. Egan RW, Umland SP, Cuss FM, Chapman RW (1996) Biology of interleukin-5 and its relevance to allergic disease. Allergy 51: 71–81

    PubMed  CAS  Google Scholar 

  238. Leckie MJ, ten Brinke A, Khan J, Diamant Z, O’Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R et al (2000) Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness and the late asthmatic response. Lancet 356: 2144–2148

    Article  PubMed  CAS  Google Scholar 

  239. Kips JC, O’Connor BJ, Langley SJ, Woodcock A, Kerstjens HA, Postma DS, Danzig M, Cuss F, Pauwels RA (2003) Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med 167: 1655–1659

    Article  PubMed  Google Scholar 

  240. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS (2003) Eosinophil’s role remains uncertain as antiinterleukin-5 only partially depletes numbers in asthmatic airways. Am J Respir Crit Care Med 167: 199–204

    Article  PubMed  Google Scholar 

  241. Gavett SH, O’Hearn DJ, Karp CL, Patel EA, Schofield BH, Finkelman FD, Wills-Karp M (1997) Interleukin-4 receptor blockade prevents airway responses induced by antigen challenge in mice. Am J Physiol 272: L253–L261

    PubMed  CAS  Google Scholar 

  242. Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB, Agosti JM, Garrison L (1999) Interleukin-4 Receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med 160: 1816–1823

    PubMed  CAS  Google Scholar 

  243. Borish LC, Nelson HS, Corren J, Bensch G, Busse WW, Whitmore JB, Agosti JM; IL-4R Asthma Study Group (2001) Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 107: 963–970

    Article  PubMed  CAS  Google Scholar 

  244. Wills-Karp M, Chiaramonte M (2003) Interleukin-13 in asthma. Curr Opin Pulm Med 9: 21–27

    Article  PubMed  CAS  Google Scholar 

  245. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, Donaldson DD (1998) Interleukin-13: central mediator of allergic asthma. Science 282: 2258–2261

    Article  ADS  PubMed  CAS  Google Scholar 

  246. Zhou Y, McLane M, Levitt RC (2001) Interleukin-9 as a therapeutic target for asthma. Respir Res 2: 80–84

    Article  PubMed  CAS  Google Scholar 

  247. Shah A, Church MK, Holgate ST (1995) Tumour necrosis factor alpha: a potential mediator of asthma. Clin Exp Allergy 25: 1038–1044

    PubMed  CAS  Google Scholar 

  248. Keatings VM, Collins PD, Scott DM, Barnes PJ (1996) Differences in interleukin-8 and tumor necrosis factor-α in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 153: 530–534

    PubMed  CAS  Google Scholar 

  249. Luster AD (1998) Chemokines — chemotactic cytokines that mediate inflammation. N Engl J Med 338: 436–445

    Article  PubMed  CAS  Google Scholar 

  250. Proudfoot AE (2002) Chemokine receptors: multifaceted therapeutic targets. Nat Rev Immunol 2: 106–115

    Article  PubMed  CAS  Google Scholar 

  251. Campbell EM, Charo IF, Kunkel SL, Strieter RM, Boring L, Gosling J, Lukacs NW (1999) Monocyte chemoat-tractant protein-1 mediates cockroach allergen-induced bronchial hyperreactivity in normal but not CCR2-/-mice: the role of mast cells. J Immunol 163: 2160–2167

    PubMed  CAS  Google Scholar 

  252. Traves SL, Culpitt S, Russell REK, Barnes PJ, Donnelly LE (2002) Elevated levels of the chemokines GRO-α and MCP-1 in sputum samples from COPD patients. Thorax 57: 590–595

    Article  PubMed  CAS  Google Scholar 

  253. Sabroe I, Peck MJ, Van Keulen BJ, Jorritsma A, Simmons G, Clapham PR, Williams TJ, Pease JE (2000) A small molecule antagonist of chemokine receptors CCR1 and CCR3. Potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. J Biol Chem 275: 25985–25992

    Article  PubMed  CAS  Google Scholar 

  254. White JR, Lee JM, Dede K, Imburgia CS, Jurewicz AJ, Chan G, Fornwald JA, Dhanak D, Christmann LT, Darcy MG et al (2000) Identification of potent, selective nonpeptide CC chemokine receptor-3 antagonist that inhibits eotaxin-, eotaxin-2-, and monocyte chemotactic protein-4-induced eosinophil migration. J Biol Chem 275: 36626–36631

    Google Scholar 

  255. Andrew DP, Chang MS, McNinch J, Wathen ST, Rihanek M, Tseng J, Spellberg JP, Elias CG 3rd (1998) STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13. J Immunol 161: 5027–5038

    PubMed  CAS  Google Scholar 

  256. White JR, Lee JM, Young PR, Hertzberg RP, Jurewicz AJ, Chaikin MA, Widdowson K, Foley JJ, Martin LD, Griswold DE, Sarau HM (1998) Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem 273: 10095–10098

    PubMed  CAS  Google Scholar 

  257. Rosenwasser LJ (1998) Biologic activities of IL-1 and its role in human disease. J Allergy Clin Immunol 102: 344–350

    PubMed  CAS  Google Scholar 

  258. Borish L, Aarons A, Rumbyrt J, Cvietusa P, Negri J, Wenzel S (1996) Interleukin-10 regulation in normal subjects and patients with asthma. J Allergy Clin Immunol 97: 1288–1296

    Article  PubMed  CAS  Google Scholar 

  259. John M, Lim S, Seybold J, Jose P, Robichaud A, O’Connor B, Barnes PJ, Chung KF (1998) Inhaled corticosteroids increase IL-10 but reduce MIP-1α, GM-CSF and IFN-γ release from alveolar macrophages in asthma. Am J Respir Crit Care Med 157: 256–262

    PubMed  CAS  Google Scholar 

  260. Takanashi S, Hasegawa Y, Kanehira Y, Yamamoto K, Fujimoto K, Satoh K, Okamura K (1999) Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers. Eur Respir J 14: 309–314

    PubMed  CAS  Google Scholar 

  261. Boguniewicz M, Martin RJ, Martin D, Gibson U, Celniker A (1995) The effects of nebulized recombinant interferon-y in asthmatic airways. J Allergy Clin Immunol 95: 133–135

    Article  PubMed  CAS  Google Scholar 

  262. Bryan SA, O’Connor BJ, Matti S, Leckie MJ, Kanabar V, Khan J, Warrington SJ, Renzetti L, Rames A, Bock JA et al (2000) Effects of recombinant human interleukin-12 on eosinophils, airway hyperreactivity and the late asthmatic response. Lancet 356: 2149–2153

    Article  PubMed  CAS  Google Scholar 

  263. Barnes PJ (1992) Modulation of neurotransmission in airways. Physiol Rev 72: 699–729

    ADS  PubMed  CAS  Google Scholar 

  264. Undem BJ, Carr MJ (2002) The role of nerves in asthma. Curr Allergy Asthma Rep 2: 159–165

    PubMed  Google Scholar 

  265. Clark JM, Abraham WM, Fishman CE, Forteza R, Ahmed A, Cortes A, Warne RL, Moore WR, Tanaka RD (1995) Tryptase inhibitors block allergen-induced airway and inflammatory responses in allergic sheep. Am J Respir Crit Care Med 152: 2076–2083

    PubMed  CAS  Google Scholar 

  266. Krishna MT, Chauhan A, Little L, Sampson K, Hawksworth R, Mant T, Djukanovic R, Lee T, Holgate S (2001) Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma. J Allergy Clin Immunol 107: 1039–1045

    Article  PubMed  CAS  Google Scholar 

  267. Luisetti M, Sturani C, Sella D, Madonini E, Galavotti V, Bruno G, Peona V, Kucich U, Dagnino G, Rosenbloom J et al (1996) MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial. Eur Respir J 9: 1482–1486

    Article  PubMed  CAS  Google Scholar 

  268. Russell RE, Culpitt SV, DeMatos C, Donnelly L, Smith M, Wiggins J, Barnes PJ (2002) Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 26: 602–609

    PubMed  CAS  Google Scholar 

  269. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD (1997) Requirement for macrophage metalloelastase for cigarette smoke-induced emphysema in mice. Science 277: 2002–2004

    Article  PubMed  CAS  Google Scholar 

  270. Cawston TE (1996) Metalloproteinase inhibitors and the prevention of connective tisue breakdown. Pharmaol Ther 70: 163–182

    CAS  Google Scholar 

  271. Carrell RW, Lomas DA (2002) Alpha1-antitrypsin deficiency-a model for conformational diseases. N Engl J Med 346: 45–53

    Article  PubMed  CAS  Google Scholar 

  272. Sallenave JM, Shulmann J, Crossley J, Jordana M, Gauldie J (1994) Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Am J Respir Cell Mol Biol 11: 733–741

    PubMed  CAS  Google Scholar 

  273. Sallenave JM, Si Tahar M, Cox G, Chignard M, Gauldie J (1997) Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human NEUTROPHILS. J Leukoc Biol 61: 695–702

    PubMed  CAS  Google Scholar 

  274. McElvaney NG, Doujaiji B, Moan MJ, Burnham MR, Wu MC, Crystal RG (1993) Pharmacokinetics of recombinant secretory leukoprotease inhibitor aerosolized to normals and individuals with cystic fibrosis. Am Rev Respir Dis 148: 1056–1060

    PubMed  CAS  Google Scholar 

  275. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, Brown TJ, Webber SE, Foster ML (2001) Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol 166: 1975–1982

    PubMed  CAS  Google Scholar 

  276. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, Consler TG, Parks DJ, Stewart EL, Willson TM et al (2002) Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 110: 93–105

    Article  PubMed  CAS  Google Scholar 

  277. Soderling SH, Beavo JA (2000) Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions. Curr Opin Cell Biol 12: 174–179

    Article  PubMed  CAS  Google Scholar 

  278. Essayan DM (2001) Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 108: 671–680

    Article  PubMed  CAS  Google Scholar 

  279. Compton CH, Gubb J, Nieman R, Edelson J, Amit O, Bakst A, Ayres JG, Creemers JP, Schultze-Werninghaus G, Brambilla C et al (2001) Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study. Lancet 358: 265–270

    Article  PubMed  CAS  Google Scholar 

  280. Gamble E, Grootendorst DC, Brightling CE, Troy S, Qiu Y, Zhu J, Parker D, Matin D, Majumdar S, Vignola AM et al (2003) Anti-inflammatory effects of the phosphodiesterase 4 inhibitor cilomilast (Ariflo) in COPD. Am J Respir Crit Care Med 168: 976–982

    Article  PubMed  Google Scholar 

  281. Jin SL, Conti M (2002) Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses. Proc Natl Acad Sci USA 99: 7628–7633

    ADS  PubMed  CAS  Google Scholar 

  282. Smith SJ, Brookes-Fazakerley S, Donnelly LE, Barnes PJ, Barnette MS, Giembycz MA (2003) Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells. Am J Physiol Lung Cell Mol Physiol 284: L279–L289

    PubMed  CAS  Google Scholar 

  283. Barnes PJ, Adcock IM (1998) Transcription factors and asthma. Eur Respir J 12: 221–234

    PubMed  CAS  Google Scholar 

  284. Manning AM (1996) Transcription factors: a new frontier in drug discovery. Drug Disc Today 1: 151–160

    CAS  Google Scholar 

  285. Kishore N, Sommers C, Mathialagan S, Guzova J, Yao M, Hauser S, Huynh K, Bonar S, Mielke C, Albee L et al (2003) A selective IKK-2 inhibitor blocks NF-kBdependent gene expression in IL-1β stimulated synovial fibroblasts. J Biol Chem 278: 32861–32871

    Article  PubMed  CAS  Google Scholar 

  286. Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298: 1911–1912

    Article  ADS  PubMed  CAS  Google Scholar 

  287. Lee JC, Kumar S, Griswold DE, Underwood DC, Votta BJ, Adams JL (2000) Inhibition of p38 MAP kinase as a therapeutic strategy. Immunopharmacology 47: 185–201

    Article  PubMed  CAS  Google Scholar 

  288. Schafer PH, Wadsworth SA, Wang L, Siekierka JJ (1999) p38α Mitogen-activated protein kinase is activated by CD28-mediated signaling and is required for IL-4 production by human CD4+CD45RO+ T cells and Th2 effector cells. J Immunol 162: 7110–7119

    PubMed  CAS  Google Scholar 

  289. Kankaanranta H, Giembycz MA, Barnes PJ, Lindsay DA (1999) SB203580, an inhibitor of p38 mitogen-activated protein kinase, enhances constitutive apoptosis of cytokine-deprived human eosinophils. J Pharmacol Exp Ther 290: 621–628

    PubMed  CAS  Google Scholar 

  290. Underwood DC, Osborn RR, Bochnowicz S, Webb EF, Rieman DJ, Lee JC, Romanic AM, Adams JL, Hay DW, Griswold DE (2000) SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol 279: L895–L902

    PubMed  CAS  Google Scholar 

  291. Costello PS, Turner M, Walters AE, Cunningham CN, Bauer PH, Downward J, Tybulewicz VL (1996) Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells. Oncogene 13: 2595–2605

    PubMed  CAS  Google Scholar 

  292. Yousefi S, Hoessli DC, Blaser K, Mills GB, Simon HU (1996) Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils. J Exp Med 183: 1407–1414

    Article  PubMed  CAS  Google Scholar 

  293. Amoui M, Draber P, Draberova L (1997) Src familyselective tyrosine kinase inhibitor, PP1, inhibits both Fc epsilonRI-and Thy-1-mediated activation of rat basophilic leukemia cells. Eur J Immunol 27: 1881–1886

    PubMed  CAS  Google Scholar 

  294. Takeyama K, Jung B, Shim JJ, Burgel PR, Dao-Pick T, Ueki IF, Protin U, Kroschel P, Nadel JA (2001) Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol 280: L165–L172

    PubMed  CAS  Google Scholar 

  295. Wakeling AE (2002) Epidermal growth factor receptor tyrosine kinase inhibitors. Curr Opin Pharmacol 2: 382–387

    PubMed  CAS  Google Scholar 

  296. Morley J (1992) Cyclosporin A in asthma therapy: a pharmacological rationale. J Autoimmunity 5(Suppl A): 265–269

    Google Scholar 

  297. Thompson AG, Starzl TC (1993) New immunosuppres-sive drugs: mechanistic insights and potential therapeutic advances. Immunol Rev 136: 71–98

    Google Scholar 

  298. Cosio MG, Majo J, Cosio MG (2002) Inflammation of the airways and lung parenchyma in COPD: role of T cells. Chest 121: 160S–165S

    Article  PubMed  CAS  Google Scholar 

  299. Yuan Q, Strauch KL, Lobb RR, Hemler ME (1996) Intracellular single-chain antibody inhibits integrin VLA-4 maturation and function. Biochem J 318: 591–596

    PubMed  CAS  Google Scholar 

  300. Lin K, Ateeq HS, Hsiung SH, Chong LT, Zimmerman CN, Castro A, Lee WC, Hammond CE, Kalkunte S, Chen LL et al (1999) Selective, tight-binding inhibitors of integrin alpha 4beta1 that inhibit allergic airway responses. J Med Chem 42: 920–934

    PubMed  CAS  Google Scholar 

  301. Romano SJ, Slee DH (2001) Targeting selectins for the treatment of respiratory diseases. Curr Opin Investig Drugs 2: 907–913

    PubMed  CAS  Google Scholar 

  302. Haczku A, Takeda K, Redai I, Hamelmann E, Cieslewicz G, Joetham A, Loader J, Lee JJ, Irvin C, Gelfand EW (1999) Anti-CD86 (B7.2) treatment abolishes allergic airway hyperresponsiveness in mice. Am J Respir Crit Care Med 159: 1638–1643

    PubMed  CAS  Google Scholar 

  303. Van Oosterhout AJ, Hofstra CL, Shields R, Chan B, Van Ark I, Jardieu PM, Nijkamp FP (1997) Murine CTLA4-IgG treatment inhibits airway eosinophilia and hyperresponsiveness and attenuates IgE upregulation in a murine model of allergic asthma. Am J Respir Cell Mol Biol 17: 386–392

    PubMed  Google Scholar 

  304. van Neerven RJ, Van de Pol MM, van der Zee JS, Stiekema FE, De Boer M, Kapsenberg ML (1998) Requirement of CD28-CD86 costimulation for allergen-specific T cell proliferation and cytokine expression. Clin Exp Allergy 28: 808–816

    PubMed  Google Scholar 

  305. Kon OM, Compton CH, Kay AB, Barnes NC (1997) A dopuble-blind placebo-controlled trial of an anti-CD4 monoclonal antibody SB210396. Am J Respir Crit Care Med 155: A203

    Google Scholar 

  306. Zhang DH, Yang L, Cohn L, Parkyn L, Homer R, Ray P, Ray A (1999) Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 11: 473–482

    Article  PubMed  CAS  Google Scholar 

  307. Hsu CH, Chua KY, Tao MH, Lai YL, Wu HD, Huang SK, Hsieh KH (1996) Immunoprophylaxis of allergeninduced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization. Nat Med 2: 540–544

    PubMed  CAS  Google Scholar 

  308. Herz U, Gerhold K, Gruber C, Braun A, Wahn U, Renz H, Paul K (1998) BCG infection suppresses allergic sensitization and development of increased airway reactivity in an animal model. J Allergy Clin Immunol 102: 867–874

    Article  PubMed  CAS  Google Scholar 

  309. Choi IS, Koh YI (2002) Therapeutic effects of BCG vaccination in adult asthmatic patients: a randomized, controlled trial. Ann Allergy Asthma Immunol 88: 584–591

    PubMed  Google Scholar 

  310. Shirtcliffe PM, Easthope SE, Cheng S, Weatherall M, Tan PL, Le Gros G, Beasley R (2001) The effect of delipidated deglycolipidated (DDMV) and heat-killed Mycobacterium vaccae in asthma. Am J Respir Crit Care Med 163: 1410–1414

    PubMed  CAS  Google Scholar 

  311. Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM (1999) Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol 162: 6284–6293

    PubMed  CAS  Google Scholar 

  312. Horner AA, Van Uden JH, Zubeldia JM, Broide D, Raz E (2001) DNA-based immunotherapeutics for the treatment of allergic disease. Immunol Rev 179: 102–118

    Article  PubMed  CAS  Google Scholar 

  313. Cookson WO (2002) Asthma genetics. Chest 121: 7S–13S

    Article  PubMed  CAS  Google Scholar 

  314. Sandford AJ, Silverman EK (2002) Chronic obstructive pulmonary disease. 1: Susceptibility factors for COPD the genotype-environment interaction. Thorax 57: 736–741

    Article  PubMed  CAS  Google Scholar 

  315. Hall IP (2000) Pharmacogenetics of asthma. Eur Respir J 15: 449–451

    PubMed  CAS  Google Scholar 

  316. Xing Z, Ohkawara Y, Jordana M, Grahern FL, Gauldie J (1996) Transfer of granulocyte-macrophage colony-stinulating factor gene to rat induces eosinophilia, monocytosis and fibrotic lesions. J Clin Invest 97: 1102–1110

    PubMed  CAS  Google Scholar 

  317. Stecenko AA, Brigham KL (2003) Gene therapy progress and prospects: alpha-1 antitrypsin. Gene Ther 10: 95–99

    Article  PubMed  CAS  Google Scholar 

  318. Nyce JW, Metzger WJ (1997) DNA antisense therapy for asthma in an animal model. Nature 385: 721–725

    Article  PubMed  CAS  Google Scholar 

  319. Sandrasagra A, Leonard SA, Tang L, Teng K, Li Y, Ball HA, Mannion JC, Nyce JW (2002) Discovery and development of respirable antisense therapeutics for asthma. Antisense Nucleic Acid Drug Dev 12: 177–181

    Article  PubMed  CAS  Google Scholar 

  320. Barnes PJ (2002) Current and future therapies for airway mucus hypersecretion. Novartis Found Symp 248: 237–249

    PubMed  CAS  Google Scholar 

  321. Sommerhoff CP, Krell RD, Williams JL, Gomes BC, Strimpler AM, Nadel JA (1991) Inhibition of human neutrophil elastase by ICI 200,355. Eur J Pharmacol 193: 153–158

    Article  PubMed  CAS  Google Scholar 

  322. Kuo H-P, Barnes PJ, Rogers DF (1992) Cigarette smoke-induced airway goblet cell secretion: dose dependent differential nerve activation. Am J Physiol 7: L161–L167

    Google Scholar 

  323. Rogers DF (2002) Pharmacological regulation of the neuronal control of airway mucus secretion. Curr Opin Pharmacol 2: 249–255

    MATH  PubMed  CAS  Google Scholar 

  324. Poole PJ, Black PN (2001) Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review. Br Med J 322: 1271–1274

    CAS  Google Scholar 

  325. Grandjean EM, Berthet P, Ruffmann R, Leuenberger P (2000) Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther 22: 209–221

    Article  PubMed  CAS  Google Scholar 

  326. Nadel JA, Burgel PR (2001) The role of epidermal growth factor in mucus production. Curr Opin Pharmacol 1: 254–258

    PubMed  CAS  Google Scholar 

  327. Inoue A, Saijo Y, Maemondo M, Gomi K, Tokue Y, Kimura Y, Ebina M, Kikuchi T, Moriya T, Nukiwa T (2003) Severe acute interstitial pneumonia and gefitinib. Lancet 361: 137–139

    PubMed  Google Scholar 

  328. Zhou Y, Shapiro M, Dong Q, Louahed J, Weiss C, Wan S, Chen Q, Dragwa C, Savio D, Huang M (2002) A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction. Novartis Found Symp 248: 150–165

    PubMed  CAS  Google Scholar 

  329. Bush A (1998) Early treatment with dornase alfa in cystic fibrosis: what are the issues? Pediatr Pulmonol 25: 79–82

    Article  PubMed  CAS  Google Scholar 

  330. Madison JM, Irwin RS (2003) Pharmacotherapy of chronic cough in adults. Expert Opin Pharmacother 4: 1039–1048

    Article  PubMed  CAS  Google Scholar 

  331. Fuller RW, Jackson DM (1990) Physiology and treatment of cough. Thorax 45: 425–430

    PubMed  CAS  Google Scholar 

  332. Choudry NB, Gray SJ, Posner J, Fuller RW (1991) The effect of 443C81, a μ-opioid receptor agonist, on the response to inhaled capsaicin in healthy volunteers. Br J Clin Pharmacol 32: 683–686

    Google Scholar 

  333. Ayik SO, Basoglu OK, Erdinc M, Bor S, Veral A, Bilgen C (2003) Eosinophilic bronchitis as a cause of chronic cough. Respir Med 97: 695–701

    PubMed  CAS  Google Scholar 

  334. Waring JP, Lacayo L, Hunter J, Katz E, Suwak B (1995) Chronic cough and hoarseness in patients with severe gastroesophageal reflux disease. Diagnosis and response to therapy. Dig Dis Sci 40: 1093–1097

    PubMed  CAS  Google Scholar 

  335. Udezue E (2001) Lidocaine inhalation for cough suppression. Am J Emerg Med 19: 206–207

    Article  PubMed  CAS  Google Scholar 

  336. Chung KF (2002) Cough: potential pharmacological developments. Expert Opin Investig Drugs 11: 955–963

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Imperial College School of Medicine, Section of Airways Disease, National Heart and Lung Institute, Dove house St, London, SW3 6LY, UK

    Peter J. Barnes

Authors
  1. Peter J. Barnes
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Faculty of Pharmacy, Department of Pharmacology and Pathophysiology, Sorbonnelaan 16, 3584 CA, Utrecht, The Netherlands

    Frans P. Nijkamp

  2. PLIVA Research Institute Ltd., Prilaz baruna Filipovića 29, HR-10 000, Zagreb, Croatia

    Michael J. Parnham

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Birkhäuser Verlag

About this chapter

Cite this chapter

Barnes, P.J. (2005). Drugs for the treatment of asthma and COPD. In: Nijkamp, F.P., Parnham, M.J. (eds) Principles of Immunopharmacology. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7408-X_19

Download citation

Publish with us

Policies and ethics

Search

Navigation